Increased mitochondrial and cytosolic antioxidant enzymes in manic episodes

array:22 ["pii" => "S0213616320300690" "issn" => "02136163" "doi" => "10.1016/j.ejpsy.2020.08.001" "estado" => "S300" "fechaPublicacion" => "2020-10-01" "aid" => "112" "copyright" => "Asociación Universitaria de Zaragoza para el Progreso de la Psiquiatría y la Salud Mental" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Eur J Psychiatry. 2020;34:181-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S0213616320300598" "issn" => "02136163" "doi" => "10.1016/j.ejpsy.2020.06.003" "estado" => "S300" "fechaPublicacion" => "2020-10-01" "aid" => "105" "copyright" => "Asociación Universitaria de Zaragoza para el Progreso de la Psiquiatría y la Salud Mental" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Eur J Psychiatry. 2020;34:189-94" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Validity and reliability of a Spanish version of the Standardised Assessment of Personality-Abbreviated Scale (SAPAS) for personality disorder screening in community mental health settings" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "189" "paginaFinal" => "194" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1508 "Ancho" => 1528 "Tamanyo" => 51030 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0075" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "The area under the curve, sensitivity, and false positives for the different cut-off points for the SAPAS score." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.E. Muñoz-Negro, R. Gómez Passalacqua, N. Pumar Alonso, J.A. Cervilla" "autores" => array:4 [ 0 => array:2 [ "nombre" => "J.E." "apellidos" => "Muñoz-Negro" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Gómez Passalacqua" ] 2 => array:2 [ "nombre" => "N." "apellidos" => "Pumar Alonso" ] 3 => array:2 [ "nombre" => "J.A." "apellidos" => "Cervilla" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213616320300598?idApp=UINPBA00004N" "url" => "/02136163/0000003400000004/v1_202010090651/S0213616320300598/v1_202010090651/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Increased mitochondrial and cytosolic antioxidant enzymes in manic episodes" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "181" "paginaFinal" => "188" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "E. Kahyaci Kiliç, R. Köse Çinar, Y. Görgülü, M.B. Sönmez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "E. Kahyaci" "apellidos" => "Kiliç" "email" => array:1 [ 0 => "scully706@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "R. Köse" "apellidos" => "Çinar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Y." "apellidos" => "Görgülü" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "M.B." "apellidos" => "Sönmez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "MD, Uzunköprü State Hospital Psychiatry Department, Edirne, 22030, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Associate Professor, MD, Trakya University, School of Medicine, Department of Psychiatry, Edirne, 22030, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Uzunköprü State Hospital Psychiatry Department, Edirne, 22030, Turkey." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1191 "Ancho" => 2065 "Tamanyo" => 75894 ] ] "descripcion" => array:1 [ "en" => "Gene expression levels of antioxidant enzymes, mean of 2−ΔΔCt. CAT, catalase; GPx, glutathione peroxidase; GS, glutathione synthetase; SOD1, SOD2, superoxide dismutase 1, 2. *p<0.05, **p<0.001." ] ] ] "textoCompleto" => "IntroductionBipolar disorder (BD) is a chronic disease that consists of repeating mania and depression episodes.<a class="elsevierStyleCrossRef" href="#bib0270">1</a> There is increasing evidence from recent studies about the role of oxidative stress in the etiology of BD.<a class="elsevierStyleCrossRefs" href="#bib0275">2–6</a> These studies about oxidative stress in BD have also been intensified concerning the activities of antioxidant enzymes and the measurement of the lipid peroxidation end-products.<a class="elsevierStyleCrossRef" href="#bib0300">7</a>Oxidative stress has been started to be defined as a disruption of redox signaling and control, despite it was previously described in terms of a balance between pro-oxidants and antioxidants.<a class="elsevierStyleCrossRef" href="#bib0305">8</a> As major components of oxidative stress, free radicals grow out in all of the tissues of the body during primarily oxidative phosphorylation in the mitochondria. Reactive oxygen species (ROS) are typically synthesized as a by-product of cellular respiration in the electron transport chain. If electrons are released from complexes of the transport chain prematurely, they transform molecular oxygen into superoxide radicals, and as a result of this biochemical reaction, various reactive oxygen species get synthesized. Enzymes like superoxide dysmutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) have the ability to save the cells from oxidative injury.<a class="elsevierStyleCrossRefs" href="#bib0310">9,10</a>Oxidative stress has been suggested to have an important role in BD pathophysiology recently. Some studies report increased peripheral markers of oxidative stress in BD and some studies report changes in the levels of antioxidant enzymes and increased lipid peroxidation end-products.<a class="elsevierStyleCrossRefs" href="#bib0290">5,11–14</a> Significant increases in antioxidant enzymes, DNA damage, protein carbonyl ingredients attributable to oxidative stress, increases in lipid peroxidation end products and nitric oxide levels were detected in some other studies.<a class="elsevierStyleCrossRefs" href="#bib0275">2,14–16</a> However, the results of these studies are contradictory. Cytosolic SOD activity was found to be high in an acute episode of BD dissimilar to a euthymic phase.<a class="elsevierStyleCrossRefs" href="#bib0320">11,13</a> Similarly, increases were reported in cytosolic SOD activity in patients during manic episodes that were not treated.<a class="elsevierStyleCrossRef" href="#bib0350">17</a> However, other studies did not find any differences between the SOD activities of the patient group and that of the healthy control group; also, some other research showed decreases in the cytosolic SOD activity in BD.<a class="elsevierStyleCrossRefs" href="#bib0355">18,19</a> Nevertheless, most studies have reported an increase in antioxidant enzyme levels.There are clinical studies that showed that mood stabilizers decrease oxidative stress markers in peripheral samples. These studies proved the therapeutic effects of mood stabilizer treatments that show antioxidant properties. Evidences show that present mood stabilizer treatments have neuroprotective effects against oxidative stress by arranging various antioxidant pathways in the cell.<a class="elsevierStyleCrossRefs" href="#bib0285">4,17,20–22</a> Another aspect of the role of oxidative stress in BD is the fact that antioxidant compounds like N-acetylcystein (NAC) have been shown to be beneficial in BD treatment.<a class="elsevierStyleCrossRefs" href="#bib0380">23–27</a> The typical antipsychotics have been found to reduce the antioxidants and increase the oxidants; in contrast, the atypical antipsychotics have been found to increase the antioxidants and reduce the oxidants.<a class="elsevierStyleCrossRefs" href="#bib0405">28–32</a>The studies about oxidative stress in BD have investigated the serum antioxidant levels till today. Conflicting results showing different serum enzyme levels have been reported. This may be a result of the variable production of enzymes under influence of numerous factors. Thus, the serum levels of these enzymes may not be showing the real tendency in BD on antioxidant enzyme production. According to a literature search, no previous human studies have examined the peripheral blood antioxidant gene expression. We hypothesized that the gene expression of the antioxidant enzymes and plasma malondialdehyde (MDA) levels that show lipid peroxidation will be altered in BD patients. In this study, the mRNA expressions of cytosolic and mitochondrial superoxide dismutase (SOD1, SOD2), catalase (CAT), glutathione synthetase (GS), glutathione peroxidase (GPx) were examined in the peripheral blood of adult, drug-free BD patients during manic and remission periods and a healthy control group. We selected the studied possible biomarkers focusing on evidence based on findings in peripheral blood.<a class="elsevierStyleCrossRefs" href="#bib0275">2,11,12,14–16,33</a> Despite the fact that studies about oxidative stress have not yet explained the pathophysiology of BD, these investigations could resolve this issue by finding markers specific to the disorder that can be searched in blood samples and following the response to treatment with biological markers.Materials and methodsPatientsThis study included 20 medication-free patients aged 18–65 years who had been diagnosed with BD-I in the past and who were currently experiencing an acute manic episode. Other inclusion criteria for the patient and control groups were as follows: having a body mass index (BMI) within a normal range (18.5–25kg/m2), having a diet similar to that of the other participants (i.e. rich in carbohydrates) and not performing physical exercise. All the patients and healthy controls stated that they were not on a special diet and did not participate in strenuous exercise activity.Exclusion criteria for the patient and the control groups were as follows: alcohol and substance (except nicotine) abuse or dependence, the presence of systemic diseases (including cardiovascular and endocrine diseases), usage of any antioxidant agents (e.g. vitamins E, C and NAC), the presence of epilepsy or severe neurological disorders and the presence of infectious diseases. For both medical and neurological diseases, exclusion was based on the results of general medical, neurological examinations and routine laboratory results. Patients who used psychotropic drugs were also excluded. Purification periods for psychotropic drugs were two weeks for oral drugs and one month for parenteral drugs; for participants who used mood stabilizer drugs, their blood levels had to be 0.The control group consisted of 20 medication-free, healthy volunteers who had no current, past or first-degree family history of a major psychiatric disorder. The participants were matched for age, gender, smoking, dietary and exercising habits.This study was performed at the Medical Faculty of Trakya University from October 2014 to April 2015. A semi-structured form was used to detect several socio-demographic data and clinical variables. The diagnosis of BD was carried out using the Structured Clinical Interview for DSM-IV-Axis I (SCID-I). The patients had to fulfill criteria for manic episodes according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Symptoms were assessed using the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS).Approval of this research was given by the ethics committee of the Medical Faculty of Trakya University. All patients or family members were given a written informed consent form before entering the study.Laboratory dataBlood samples were obtained using vacutainer tubes from the patients and the controls between 08:00 and 10:00 a.m., and the samples were centrifuged at 3000rpm for 15min and stored at −80° C for further analysis. The samples from the patients were taken the day after their admittance to the inpatient clinic. Blood samples were taken again when the patients fulfilled the remission criteria as defined by their total score on the YMRS of <4.<a class="elsevierStyleCrossRef" href="#bib0435">34</a>Determination of gene expression levelsThe mRNA expression levels were measured using the quantitative real-time polymerase chain reaction (qRT-PCR). The total RNA was isolated from the whole blood using the PureLink® RNA Mini Kit (Life Technologies, USA) according to the manufacturer's instructions. The extracted RNA concentrations were measured by the Qubit® Fluorometer (Life Technologies, USA). The first strand of cDNA was synthesized using a High Capacity cDNA Reverse Transcription Kit (Life Technologies, USA). The c DNA synthesis was performed using a thermal cycler Applied Biosystems® Veriti®. The gene expression levels of the antioxidant enzymes were analyzed by qRT-PCR using the SYBR® Select Master Mix (Life Technologies, USA) on an ABI Step One Plus Real-Time PCR system. PCR Cycling: 2min at 50°C and 10min at 95°C, 40 cycles at 95°C for 15s, and 60°C for 60s. Glyceraldehydes 3-phosphate dehydrogenase (GADPH) [Forward (5′-AATTCCGATCTTCGACATGG3-′) Reverse (5′-GAAAAAGCGGCAGTCGTAAT-3′)] was used as the housekeeping gene. The primers used in the gene expression are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The comparative cycle threshold (2−ΔΔCt) method was used for the gene expression analysis of data measured by PCR.<a class="elsevierStyleCrossRef" href="#bib0440">35</a> Ct (threshold cycle) indicated the fractional cycle number at which the amount of amplified target reached a fixed threshold. ΔCt corresponded to normalized Ct values and was equal to the difference in cycle thresholds between the target (gene expressions of predetermined molecules) and reference genes (housekeeping genes). GAPDH was used as the housekeeping gene in our research. ΔΔCt corresponded to the difference between the expression level of the average ΔCt of the patient group and that of the control group. 2−ΔΔCt denoted the fold change in the expression level change of the following measures of the patient group compared to the control group. All analyses were performed in the same laboratory.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Determination of plasma MDA levelsLipid peroxidation levels were determined by measuring the end product of lipid peroxidation MDA. Plasma MDA values were calculated using the extinction coefficient of the MDA-thiobarbituric acid complex at 532nm. Levels of plasma MDA were measured by the thiobarbituric acid (TBA) method, which was modified from Young et al.’s<a class="elsevierStyleCrossRef" href="#bib0445">36</a> method. Peroxidation was measured as the production of MDA, which in combination with TBA forms a pink chromogen compound whose absorbance at 532nm was measured. The MDA results were expressed as nmol/ml.Statistical analysisData were analyzed using the SPSS 20.0 version for Windows statistical software. The Kolmogrov–Smirnov test was used to compare the observed cumulative distribution functions; our sample presented abnormal distribution. Non-parametric statistical methods were used to analyze the data, and groups were compared using Mann–Whitney U and Wilcoxon tests. Categorical variables were analyzed with a chi-square test, and the relationship between the biochemical and clinical variables was assessed using spearman correlation. The results were expressed as the means±standard deviation (SD). A p value of less than 0.05 was used to indicate statistical significance.ResultsDemographicsTwenty inpatients with BD in a manic episode (n=20) and healthy volunteers (n=20) were included in this study. None of the subjects in either group had comorbid diseases. The mean ages of the patient and control groups were similar (31.75±8.23 and 31.85±7.31, respectively; p=0.968). Each group was composed of 14 males and 6 females. The average BMI of the patients and controls was within the normal range (24.3kg/m2±3.2kg/m2, 24.7kg/m2±3.0kg/m2) and was similar between the two groups (p=0.669). In the patient group, the time to reach remission was 9.3±1.5 weeks. The clinical characteristics of the BD patients and the drugs used during remission are included in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Comparison of mania and controlsThe bipolar patients in a manic phase had higher mean gene expression levels of SOD2, CAT, GPx and GS than the healthy subjects. The gene expression levels of SOD1 showed no significant difference between the two groups (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The gene expression levels of antioxidant enzymes had no significant association with the YMRS scores (for CAT, r=0.360; for GPx, r=0.230; for GS, r=0.231; for SOD1, r=0.064; for SOD2, r=0.241) (p>0.05). The plasma levels of MDA showed no significant difference between the two groups (manic group=0.113±0.180nmol/ml, control group=0.064±0.023nmol/ml; p=0.935).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Comparison of mania and remissionTwenty bipolar inpatients received follow-up appointments, in which the gene expression levels of their antioxidant enzymes and the plasma levels of their MDA were measured after treatment. The patients’ (16 men and 4 women) mean hospitalization duration was 36±7.82 days. The YMRS scores at baseline were 30.95±8.33, and 2.10±1.11 at the end point. We found significantly decreased changes in the expression levels of GPx in bipolar patients who had received treatment (p=0.003), while other markers (SOD1,2, CAT, GPx, GS) showed no significant changes after treatment (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The plasma levels of MDA at baseline were 0.113±0.180nmol/ml and 0.073±0.030nmol/ml at the end point, showing no significant change after treatment (p=0.654).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>DiscussionThe most important finding in this study is that bipolar patients in a manic phase had significantly higher gene expression levels of SOD2, CAT, GPx and GS than the healthy controls. The expression levels of GPx mRNA decreased during the remission period compared to the levels in the manic state. It can be supposed that this dissimilarity formed as a compensating mechanism against the oxidative stress that increases during a manic episode.Conflicting results were detected in clinical studies that investigated antioxidant enzyme levels in BD. Different and conflicting data in the literature could be a result of racial differences, diet properties, lifestyles that influence oxidative stress, differences between disease episodes, treatment differences and procedures used in studies.<a class="elsevierStyleCrossRefs" href="#bib0325">12,14,18</a> Regarding the studies comparing patients with BD in a manic episode and healthy subjects, some show no increase, some show a decrease and others show no change in serum or erythrocyte SOD activities at all.<a class="elsevierStyleCrossRefs" href="#bib0320">11,13,17,37</a>Detecting no difference between the SOD activities of patient groups and healthy subjects, despite expectations that those of the patient groups would increase, can be interpreted as an indication that the changes at transcriptional levels were not actualized at the protein level. Since there is no data about differences between the gene expression levels of these enzymes in BD, in the current study, we aimed to investigate the SOD1 and SOD2 gene expression levels in order to fill this empty space in the literature. There are studies in which cytosolic SOD levels were detected in BD patients that were similar to that of the control group.<a class="elsevierStyleCrossRefs" href="#bib0285">4,38</a> There were no significantly important differences between the SOD2 levels in a study in which postmortem prefrontal cortex samples of BD patients, schizophrenia patients and healthy subjects were evaluated.<a class="elsevierStyleCrossRef" href="#bib0460">39</a> Furthermore, there were no differences between the SOD1 and SOD2 levels of the postmortem dorsolateral prefrontal cortex cross-sections from BD patients, schizophrenia patients and healthy subjects.<a class="elsevierStyleCrossRef" href="#bib0465">40</a>In most of the studies, SOD enzyme levels were not evaluated separately as cytosolic or mitochondrial. In our study, it was discovered that mitochondrial SOD gene enzyme levels were higher in manic patients than in healthy subjects. There were no statistically significant differences in cytosolic SOD levels between the two groups. The increase that was detected in the mitochondrial SOD expression level, which is the first antecedent of antioxidant defence, shows that oxidative stress may be increasing during the acute episode of the disease; antioxidant enzymes prevented this from happening in our study.Increases were detected in the CAT gene expression levels during manic episodes compared to the controls in our study. This increase can be interpreted as a compensating response that is promoted synchronously with the increase in SOD expression that grows as the first defence step against oxidative stress. Some studies showed that there were increases or decreases in serum CAT levels during BD manic episodes.<a class="elsevierStyleCrossRefs" href="#bib0320">11,14,17,19,38</a>The GPx expression levels were higher in manic patients when compared to the controls. This increased levels may have a relation with increased expression of mitochondrial SOD that removes H2O2. A positive correlation was found between gene expression levels of SOD2 and GPx. Variable results were found in studies investigating GPx activity. For example, GPx activity was found significantly high during euthymic phase by Andreazza et al.<a class="elsevierStyleCrossRef" href="#bib0320">11</a> GPx levels were also found significantly higher in BD patients during depressive phase when compared to the controls.<a class="elsevierStyleCrossRef" href="#bib0455">38</a> However, some studies found unchanged GPx activity between BP patients and healthy controls.<a class="elsevierStyleCrossRefs" href="#bib0325">12,14,41</a>The significant increase in GS expression levels in the manic patients when compared to the control group may be due to the fact that glutathione synthesis plays an important role in the defence mechanism, which is composed of antioxidant enzymes against oxidative stress. Also, some studies show decreases in the glutathione levels of BD.<a class="elsevierStyleCrossRefs" href="#bib0360">19,41</a> When BD patients in early or late stages were compared with each other in order to evaluate the effect of BD duration on antioxidant enzymes, there were no significant differences between the two groups regarding the gene expression levels of their antioxidant enzymes. However, an increase in antioxidant enzymes during the late stage was detected in antioxidant enzymes.<a class="elsevierStyleCrossRef" href="#bib0475">42</a> This difference between this study and our study could be a result of the shorter disease duration of the sample that composes our study.In the current study, the antioxidant gene expression levels of the patients who were in manic episode and subsequent remission phase were found to be similar except for GPx. No differences were detected between the SOD, CAT and GPx levels before and after treatment in the patient group,<a class="elsevierStyleCrossRef" href="#bib0480">43</a> the fact that there were no differences in our study either could be interpreted as a result of continuing oxidative stress during a remission phase and continuing the compensatory response at the level of gene expression. In contrast, the CAT, GPx and MDA levels were found to show significant change after mood stabilizer treatment in BD patients.<a class="elsevierStyleCrossRef" href="#bib0285">4</a> Also, their TBARS and SOD levels decreased significantly after six months of lithium treatment for BD patients during depressive episodes.<a class="elsevierStyleCrossRef" href="#bib0455">38</a> In our study, patients were on different antipsychotic drugs, in addition to lithium and valproate. It was discovered that typical antipsychotics were increasing oxidants and decreasing antioxidants; conversely, atypical antipsychotics were decreasing oxidants and increasing antioxidants.<a class="elsevierStyleCrossRefs" href="#bib0405">28,30,31,44</a> Ninety-five percent of the manic patients in our study were on atypical antipsychotic treatment; from the results, it can be supposed that atypical antipsychotic drugs had a mixed effect on their gene expression level changes during their remission phase.We found similar levels of plasma MDA between patient and control groups in our study. Our findings are discordant with the results of the meta-analysis,<a class="elsevierStyleCrossRef" href="#bib0310">9</a> which found that thiobarbituric acid reactive substances (TBARS) increase in BD. However, some recent studies did not find any difference between the TBARS levels in BD like our study did.<a class="elsevierStyleCrossRefs" href="#bib0335">14,45,46</a> Plasma TBARS levels were found to be similar to that of the control group in BD type I and type II, this similarity was explained by the simultaneous CAT and GPx increase.<a class="elsevierStyleCrossRef" href="#bib0455">38</a>The plasma MDA levels of manic episode patients that have gone into remission after mood stabilizer treatment were detected as similar to their levels before treatment in our study. Mood stabilizer drugs that were given to patients in various studies were reported to produce some effects that helped decrease oxidative lipid damage. In the studies that were done with rat models, in which mania episodes were induced by amphetamine, lithium treatment was reported to decrease lipid peroxidation.<a class="elsevierStyleCrossRefs" href="#bib0500">47–49</a> Clinical studies have been shown to reduce the plasma TBARS levels of lithium treatment in BD patients.<a class="elsevierStyleCrossRefs" href="#bib0350">17,38,50,51</a> The effect of only mood stabilizer treatment on oxidative lipid damage was considered in the inspected studies, but various antipsychotic treatments were given to patients for treatment of manic episodes. This situation may have had an effect on the MDA levels that were measured during remission episodes.Bipolar patients are known to have higher rates of smoking than the general population.<a class="elsevierStyleCrossRef" href="#bib0525">52</a> Nicotine exposure was shown to increase cytosolic ROS levels and leads to oxidative stress in numerous studies on cultured cells. The levels and activities of antioxidant enzymes such as SOD, CAT, GR and GPx were reported to decrease following nicotine exposure.<a class="elsevierStyleCrossRef" href="#bib0530">53</a> The subjects with substance abuse and dependence were excluded in our BD and control groups but the subjects with nicotine abuse and dependence were not excluded. Nearly all of our manic patients (80%; n=16) and controls (70%; n=14) were smokers. Therefore, the effects of smoking on oxidative stress molecules were not ruled out in our study.Our study has some limitations: First, only the manic episodes of BD were investigated. Also, this research used a small sample size, and obtained information regarding the patients’ diet and exercise habits based on subjective self-reports. Additionally, another limitation was the variability of the antipsychotic treatments given to our manic episode patient group and the inability of excluding the drug's effects. We analyzed mood stabilizing drug blood levels before enrolling the participants into the study. However, analysing antipsychotic drug blood levels were impossible due to laboratory limitations.Since there is no data about the differences between the gene expression levels of the enzymes in BD, we aimed to investigate the SOD1 and SOD2 gene expression levels in order to fill this empty space in the literature. A strong point of our research is the study population, since it comprised BD patients with severe mania and no psychotropic drug use. Also, it involved the subsequent remission period of the same patients and healthy controls.ConclusionsDetection of increases in CAT, GPx, GS and SOD2 in the gene expression levels during a manic episode may be due to the activation of antioxidant systems against oxidative stress that increases in patients. Research shows that oxidative stress plays an important role in BD pathophysiology, and the drugs that decrease oxidative stress can give hope for future treatment modalities of BD. Further research needs to be conducted in bigger samples than ours concerning antioxidant gene expression in all episodes of BD with gene expressions. Investigation of these differences in groups in which disorder did not yet arise, but of higher risk for BD and additional research specifically about mitochondrial SOD, GS, GPx and CAT enzymes could provide further information about the role of the differences in BD etiopathogenesis; as a result, newer diagnosis, treatment and follow-up options could be developed.To the best of our knowledge, this is the first study in the field of psychiatry to show gene expression changes in oxidative stress biomarkers of BD patients and treatment-related changes in the levels of these biomarkers. Follow-up appointments with the same patient group will be needed in order to verify these findings.Ethical considerationsThis study was approved by the local ethics committee of the Trakya University Faculty of Medicine (Project No. 2014/113). All procedures followed were in accordance with The Code of Ethics of the World Medical Association and with the Helsinki Declaration.FundingThis study was supported by grant form the Scientific Research Projects Unit of the Trakya University, Edirne, Turkey (Project No.: 2014/100).Conflict of interestThe authors have no conflict of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1396223" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1279408" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Laboratory data" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Determination of gene expression levels" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Determination of plasma MDA levels" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Demographics" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Comparison of mania and controls" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Comparison of mania and remission" ] ] ] 5 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions" ] 7 => array:2 [ "identificador" => "sec0070" "titulo" => "Ethical considerations" ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-12-09" "fechaAceptado" => "2020-08-10" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1279408" "palabras" => array:5 [ 0 => "Bipolar disorder" 1 => "Oxidative stress" 2 => "Malondialdehyde" 3 => "Antioxidant enzymes" 4 => "Gene expression" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Background and objectivesAn increasing number of studies have been conducted to investigate the role of oxidative stress in the pathophysiology of bipolar disorder (BD). The aim of our study was to detect the levels of plasma malondialdehyde and the gene expression of antioxidant enzymes in BD patients during manic period and to assess the changes of these markers during the subsequent remission period. MethodsThis study involved 20 drug-free, hospitalized patients with BD type I who met the manic episode diagnostic criteria according to DSM-5, as well as 20 age-sex matched healthy controls. As a marker of lipid damage, malondialdehyde plasma levels were measured by the thiobarbituric acid method; mRNA expression levels of catalase (CAT), glutathione peroxidase (GPx), glutathione synthetase (GS), superoxide dismutase (SOD1) and mitochondrial superoxide dismutase (SOD2) were measured by real-time quantitative PCR from peripheral whole blood samples. ResultsIn a manic episode, the expression levels of CAT, GPx, GS and SOD2 were higher in the patients than the healthy controls. With treatment, only the GPx levels decreased significantly. The malondialdehyde and SOD1 levels did not differ between the patients and controls, and in the patient group, they did not differ between the mania and remission periods. ConclusionThis is the first study that has assessed the mRNA expression levels of antioxidant enzymes in patients with BD type I. The data from this study suggests that there is an increase in the expression of antioxidant enzymes as a response to oxidative stress in BD, and that the gene expression levels of these antioxidant enzymes could be potential biomarkers for manic phase of the disorder." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1191 "Ancho" => 2065 "Tamanyo" => 75894 ] ] "descripcion" => array:1 [ "en" => "Gene expression levels of antioxidant enzymes, mean of 2−ΔΔCt. CAT, catalase; GPx, glutathione peroxidase; GS, glutathione synthetase; SOD1, SOD2, superoxide dismutase 1, 2. *p<0.05, **p<0.001." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SOD1, SOD2, superoxide dismutase 1, 2; CAT, catalase; GS, glutathione synthetase; GPx, glutathione peroxidase." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SOD1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Forward (5′-GTTCGGTGACAACACCAATG-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reverse (5′-GGAGTCGGTGATGTTGACCT-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SOD2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Forward (5′-TCTGAAGAAGGCCATCGAGT-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reverse (5′-GCAGATAGTAGGCGTGCTCC-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CAT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Forward (5′-TACGAGCAGGCCAAGAAGTT-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reverse (5′-ACCTTGTACGGGCAGTTCAC-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Forward (5′-TGGGACCAGCAAGTAAAACC-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reverse (5′-TCGCGAATG TAGAACTCGTG-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GPx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Forward (5′-TTCCCGTGCAACCAGTTTG-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reverse (5′-TTCACCTCGCACTTCTCGAA-3′) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2396189.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Primers of antioxidant enzymes." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Values are given as mean±standard deviation or number (%). BMI, body mass index; YMRS, Young Mania Rating Scale.*p<0.05." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients (n=20) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controls (n=20) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31.75±8.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31.85±7.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.968 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gender (male/female) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14/6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14/6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Education, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.10±2.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.70±3.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.547 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Duration of illness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.40±7.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The number of manic episodes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.10±2.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The number of depressive episodes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.00±0.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hospitalization number \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.85±2.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI (kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.33±3.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.76±3.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.669 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Current smoking (yes/no) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14/6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.716 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">YMRS at admission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.95±8.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">YMRS at the end of the study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.10±1.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Psychotic features \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drug use at the end of the study</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lithium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Valproat \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risperidone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ketiapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Olanzapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aripiprazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Haloperidol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2396188.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographics and clinical characteristics of BD and control group." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "CAT, catalase; GPx, glutathione peroxidase; GS, glutathione synthetase; SOD1, SOD2, superoxide dismutase 1, 2.The gene expression levels of controls are 1 (according to 2−ΔΔCt method) and not represented in the table.p values are calculated by using Mann–Whitney test." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients in manic phase \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CAT \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GPx \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GS \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SOD1 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SOD2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean±sd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.23±38.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.21±1.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.47±36.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.08±2.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.18±46.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.874 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.031 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.837 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p values \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.022* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001** \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001** \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.682 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001** \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2396190.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Gene expression levels of antioxidant enzymes." ] ] 4 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Median values are given in the table. SOD1, SOD2, superoxide dismutase 1, 2; CAT, catalase; GS, glutathione synthetase; GPx, glutathione peroxidase; MDA, malondialdehyde; YMRS, Young Mania Rating Scale." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable (n=20) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CAT \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GPx \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GS \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SOD1 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SOD2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MDA(nmol/ml) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">YMRS scores \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baseline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.874 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.031 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.837 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.061 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.95±8.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Endpoint \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.524 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.042 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.323 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.195 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.572 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.070 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.10±1.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p value \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.650 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.281 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.155 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.943 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.654 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2396191.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "p<0.05." ] ] ] "descripcion" => array:1 [ "en" => "Changes in the gene expression levels of antioxidant enzymes and plasma MDA levels after teatment in bipolar patients." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:53 [ 0 => array:3 [ "identificador" => "bib0270" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.H. Belmaker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra035354" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2004" "volumen" => "351" "numero" => "5" "paginaInicial" => "476" "paginaFinal" => "486" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15282355" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0275" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Berk" 1 => "F. Kapczinski" 2 => "A.C. Andreazza" 3 => "O.M. Dean" 4 => "F. Giorlando" 5 => "M. Maes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neubiorev.2010.10.001" "Revista" => array:7 [ "tituloSerie" => "Neurosci Biobehav Rev" "fecha" => "2011" "volumen" => "35" "numero" => "3" "paginaInicial" => "804" "paginaFinal" => "817" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20934453" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0280" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An updated meta-analysis of oxidative stress markers in bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N.C. Brown" 1 => "A.C. Andreazza" 2 => "L.T. Young" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.psychres.2014.04.005" "Revista" => array:7 [ "tituloSerie" => "Psychiatry Res" "fecha" => "2014" "volumen" => "218" "numero" => "1–2" "paginaInicial" => "61" "paginaFinal" => "68" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24794031" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0285" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antioxidant enzyme activities and oxidative stress in affective disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.E. Ozcan" 1 => "M. Gulec" 2 => "E. Ozerol" 3 => "R. Polat" 4 => "O. Akyol" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00004850-200403000-00006" "Revista" => array:7 [ "tituloSerie" => "Int Clin Psychopharmacol" "fecha" => "2004" "volumen" => "19" "numero" => "2" "paginaInicial" => "89" "paginaFinal" => "95" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15076017" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0290" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of oxidative stress in the pathophysiology of bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.V. Steckert" 1 => "S.S. Valvassori" 2 => "M. Moretti" 3 => "F. Dal-Pizzol" 4 => "J. Quevedo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11064-010-0195-2" "Revista" => array:7 [ "tituloSerie" => "Neurochem Res" "fecha" => "2010" "volumen" => "35" "numero" => "9" "paginaInicial" => "1295" "paginaFinal" => "1301" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20499165" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0295" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.F. Wang" 1 => "L. Shao" 2 => "X. Sun" 3 => "L.T. Young" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1399-5618.2009.00717.x" "Revista" => array:7 [ "tituloSerie" => "Bipolar Disord" "fecha" => "2009" "volumen" => "11" "numero" => "5" "paginaInicial" => "523" "paginaFinal" => "529" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19624391" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0300" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oxidative stress in bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "V. Tang" 1 => "J. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Biochem Anal Biochem" "fecha" => "2012" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0305" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Redefining oxidative stress" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.P. Jones" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/ars.2006.8.1865" "Revista" => array:7 [ "tituloSerie" => "Antioxid Redox Signal" "fecha" => "2006" "volumen" => "8" "numero" => "9-10" "paginaInicial" => "1865" "paginaFinal" => "1879" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16987039" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0310" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oxidative stress markers in bipolar disorder: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.C. Andreazza" 1 => "M. Kauer-Sant’Anna" 2 => "B.N. Frey" 3 => "D.J. Bond" 4 => "F. Kapczinski" 5 => "L.T. Young" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jad.2008.04.013" "Revista" => array:7 [ "tituloSerie" => "J Affect Disord" "fecha" => "2008" "volumen" => "111" "numero" => "2–3" "paginaInicial" => "135" "paginaFinal" => "144" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18539338" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0315" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peroxide detoxification by brain cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R. Dringen" 1 => "P.G. Pawlowski" 2 => "J. Hirrlinger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jnr.20280" "Revista" => array:7 [ "tituloSerie" => "J Neurosci Res" "fecha" => "2005" "volumen" => "79" "numero" => "1–2" "paginaInicial" => "157" "paginaFinal" => "165" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15573410" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0320" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum S100B and antioxidant enzymes in bipolar patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.C. Andreazza" 1 => "C. Cassini" 2 => "A.R. Rosa" 3 => "M.C. Leite" 4 => "L.M. de Almeida" 5 => "P. Nardin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jpsychires.2006.07.013" "Revista" => array:7 [ "tituloSerie" => "J Psychiatr Res" "fecha" => "2007" "volumen" => "41" "numero" => "6" "paginaInicial" => "523" "paginaFinal" => "529" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16956621" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0325" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Kuloglu" 1 => "B. Ustundag" 2 => "M. Atmaca" 3 => "H. Canatan" 4 => "A.E. Tezcan" 5 => "N. Cinkilinc" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cbf.940" "Revista" => array:7 [ "tituloSerie" => "Cell Biochem Funct" "fecha" => "2002" "volumen" => "20" "numero" => "2" "paginaInicial" => "171" "paginaFinal" => "175" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11979513" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0330" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Kunz" 1 => "C.S. Gama" 2 => "A.C. Andreazza" 3 => "M. Salvador" 4 => "K.M. Cereser" 5 => "F.A. Gomes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pnpbp.2008.07.001" "Revista" => array:7 [ "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry" "fecha" => "2008" "volumen" => "32" "numero" => "7" "paginaInicial" => "1677" "paginaFinal" => "1681" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18657586" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0335" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.K. Ranjekar" 1 => "A. Hinge" 2 => "M.V. Hegde" 3 => "M. Ghate" 4 => "A. Kale" 5 => "S. Sitasawad" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0165-1781(03)00220-8" "Revista" => array:7 [ "tituloSerie" => "Psychiatry Res" "fecha" => "2003" "volumen" => "121" "numero" => "2" "paginaInicial" => "109" "paginaFinal" => "122" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14656446" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0340" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "DNA damage in bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.C. Andreazza" 1 => "B.N. Frey" 2 => "B. Erdtmann" 3 => "M. Salvador" 4 => "F. Rombaldi" 5 => "A. Santin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.psychres.2006.03.025" "Revista" => array:7 [ "tituloSerie" => "Psychiatry Res" "fecha" => "2007" "volumen" => "153" "numero" => "1" "paginaInicial" => "27" "paginaFinal" => "32" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17582509" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0345" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of the arginine-nitric oxide pathway in the pathogenesis of bipolar affective disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Yanik" 1 => "H. Vural" 2 => "H. Tutkun" 3 => "S.S. Zoroglu" 4 => "H.A. Savas" 5 => "H. Herken" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00406-004-0453-x" "Revista" => array:7 [ "tituloSerie" => "Eur Arch Psychiatry Clin Neurosci" "fecha" => "2004" "volumen" => "254" "numero" => "1" "paginaInicial" => "43" "paginaFinal" => "47" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14991378" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0350" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: a possible role for lithium antioxidant effects" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Machado-Vieira" 1 => "A.C. Andreazza" 2 => "C.I. Viale" 3 => "V. Zanatto" 4 => "V. Cereser Jr." 5 => "R. da Silva Vargas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neulet.2007.05.016" "Revista" => array:7 [ "tituloSerie" => "Neurosci Lett" "fecha" => "2007" "volumen" => "421" "numero" => "1" "paginaInicial" => "33" "paginaFinal" => "36" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17548157" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0355" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activities of superoxide dismutase and glutathione peroxidase in schizophrenic and manic-depressive patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.S. Abdalla" 1 => "H.P. Monteiro" 2 => "J.A. Oliveira" 3 => "E.J. Bechara" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Clin Chem" "fecha" => "1986" "volumen" => "32" "numero" => "5" "paginaInicial" => "805" "paginaFinal" => "807" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2870827" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0360" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduced antioxidant defense systems in schizophrenia and bipolar I disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Raffa" 1 => "S. Barhoumi" 2 => "F. Atig" 3 => "C. Fendri" 4 => "A. Kerkeni" 5 => "A. Mechri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pnpbp.2012.07.013" "Revista" => array:7 [ "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry" "fecha" => "2012" "volumen" => "39" "numero" => "2" "paginaInicial" => "371" "paginaFinal" => "375" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22841966" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0365" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment with lithium, alone or in combination with olanzapine, relieves oxidative stress but increases atherogenic lipids in bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Aliyazicioglu" 1 => "B. Kural" 2 => "M. Colak" 3 => "S.C. Karahan" 4 => "S. Ayvaz" 5 => "O. Deger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1620/tjem.213.79" "Revista" => array:7 [ "tituloSerie" => "Tohoku J Exp Med" "fecha" => "2007" "volumen" => "213" "numero" => "1" "paginaInicial" => "79" "paginaFinal" => "87" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17785956" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0370" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of lithium on oxidative stress parameters in healthy subjects" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Khairova" 1 => "r.R. Pawa" 2 => "G. Salvadore" 3 => "M.F. Juruena" 4 => "R.T. de Sousa" 5 => "M.G. Soeiro-de-Souza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3892/mmr.2011.732" "Revista" => array:7 [ "tituloSerie" => "Mol Med Rep" "fecha" => "2012" "volumen" => "5" "numero" => "3" "paginaInicial" => "680" "paginaFinal" => "682" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22200861" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0375" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Selek" 1 => "H.A. Savas" 2 => "H.S. Gergerlioglu" 3 => "F. Bulbul" 4 => "E. Uz" 5 => "M. Yumru" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jad.2007.08.006" "Revista" => array:7 [ "tituloSerie" => "J Affect Disord" "fecha" => "2008" "volumen" => "107" "numero" => "1–3" "paginaInicial" => "89" "paginaFinal" => "94" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17869345" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0380" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "N-acetyl cysteine for depressive symptoms in bipolar disorder – a double-blind randomized placebo-controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Berk" 1 => "D.L. Copolov" 2 => "O. Dean" 3 => "K. Lu" 4 => "S. Jeavons" 5 => "I. Schapkaitz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.biopsych.2008.04.022" "Revista" => array:7 [ "tituloSerie" => "Biol Psychiatry" "fecha" => "2008" "volumen" => "64" "numero" => "6" "paginaInicial" => "468" "paginaFinal" => "475" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18534556" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0385" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Berk" 1 => "O. Dean" 2 => "S.M. Cotton" 3 => "C.S. Gama" 4 => "F. Kapczinski" 5 => "B.S. Fernandes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jad.2011.06.005" "Revista" => array:7 [ "tituloSerie" => "J Affect Disord" "fecha" => "2011" "volumen" => "135" "numero" => "1–3" "paginaInicial" => "389" "paginaFinal" => "394" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21719110" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0390" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O.M. Dean" 1 => "M. van den Buuse" 2 => "A.I. Bush" 3 => "D.L. Copolov" 4 => "F. Ng" 5 => "S. Dodd" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2174/092986709788803060" "Revista" => array:7 [ "tituloSerie" => "Curr Med Chem" "fecha" => "2009" "volumen" => "16" "numero" => "23" "paginaInicial" => "2965" "paginaFinal" => "2976" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19689277" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0395" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of antioxidant N-acetyl-L-cysteine on behavioral changes and neurotoxicity in rats after administration of methamphetamine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Fukami" 1 => "K. Hashimoto" 2 => "K. Koike" 3 => "N. Okamura" 4 => "E. Shimizu" 5 => "M. Iyo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.brainres.2004.04.072" "Revista" => array:7 [ "tituloSerie" => "Brain Res" "fecha" => "2004" "volumen" => "1016" "numero" => "1" "paginaInicial" => "90" "paginaFinal" => "95" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15234256" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0400" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "N-acetyl cysteine add-on treatment for bipolar II disorder: a subgroup analysis of a randomized placebo-controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.V. Magalhaes" 1 => "O.M. Dean" 2 => "A.I. Bush" 3 => "D.L. Copolov" 4 => "G.S. Malhi" 5 => "K. Kohlmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jad.2010.08.001" "Revista" => array:7 [ "tituloSerie" => "J Affect Disord" "fecha" => "2011" "volumen" => "129" "numero" => "1–3" "paginaInicial" => "317" "paginaFinal" => "320" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20800897" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0405" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mood stabilizing drugs lamotrigine and olanzapine increase expression and activity of glutathione S-transferase in primary cultured rat cerebral cortical cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Bakare" 1 => "L. Shao" 2 => "J. Cui" 3 => "L.T. Young" 4 => "J.F. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neulet.2009.03.022" "Revista" => array:7 [ "tituloSerie" => "Neurosci Lett" "fecha" => "2009" "volumen" => "455" "numero" => "1" "paginaInicial" => "70" "paginaFinal" => "73" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19429109" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0410" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Haloperidol and clozapine, but not olanzapine, induces oxidative stress in rat brain" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Reinke" 1 => "M.R. Martins" 2 => "M.S. Lima" 3 => "J.C. Moreira" 4 => "F. Dal-Pizzol" 5 => "J. Quevedo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neulet.2004.09.032" "Revista" => array:7 [ "tituloSerie" => "Neurosci Lett" "fecha" => "2004" "volumen" => "372" "numero" => "1-2" "paginaInicial" => "157" "paginaFinal" => "160" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15531108" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0415" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparative study of oxidative stress and interrelationship of important antioxidants in haloperidol and olanzapine treated patients suffering from schizophrenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "O.P. Singh" 1 => "I. Chakraborty" 2 => "A. Dasgupta" 3 => "S. Datta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/0019-5545.43627" "Revista" => array:7 [ "tituloSerie" => "Indian J Psychiatry" "fecha" => "2008" "volumen" => "50" "numero" => "3" "paginaInicial" => "171" "paginaFinal" => "176" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19742187" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0420" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Olanzapine and quetiapine protect PC12 cells from beta-amyloid peptide(25-35)-induced oxidative stress and the ensuing apoptosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H. Wang" 1 => "H. Xu" 2 => "L.E. Dyck" 3 => "X.M. Li" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jnr.20570" "Revista" => array:7 [ "tituloSerie" => "J Neurosci Res" "fecha" => "2005" "volumen" => "81" "numero" => "4" "paginaInicial" => "572" "paginaFinal" => "580" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15948179" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0425" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of risperidone and haloperidol on superoxide dismutase and nitric oxide in schizophrenia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X.Y. Zhang" 1 => "D.F. Zhou" 2 => "Y.C. Shen" 3 => "P.Y. Zhang" 4 => "W.F. Zhang" 5 => "J. Liang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neuropharm.2011.12.014" "Revista" => array:7 [ "tituloSerie" => "Neuropharmacology" "fecha" => "2012" "volumen" => "62" "numero" => "5–6" "paginaInicial" => "1928" "paginaFinal" => "1934" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22227558" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0430" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "F. Kapczinski" 1 => "B.N. Frey" 2 => "A.C. Andreazza" 3 => "M. Kauer-Sant’Anna" 4 => "A.B. Cunha" 5 => "R.M. Post" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Braz J Psychiatr" "fecha" => "2008" "volumen" => "30" "numero" => "3" "paginaInicial" => "243" "paginaFinal" => "245" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0435" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The empirical redefinition of the psychometric criteria for remission in bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Berk" 1 => "F. Ng" 2 => "W.V. Wang" 3 => "J.R. Calabrese" 4 => "P.B. Mitchell" 5 => "G.S. Malhi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jad.2007.06.011" "Revista" => array:7 [ "tituloSerie" => "J Affect Disord" "fecha" => "2008" "volumen" => "106" "numero" => "1-2" "paginaInicial" => "153" "paginaFinal" => "158" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17655936" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0440" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.J. Livak" 1 => "T.D. Schmittgen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/meth.2001.1262" "Revista" => array:7 [ "tituloSerie" => "Methods" "fecha" => "2001" "volumen" => "25" "numero" => "4" "paginaInicial" => "402" "paginaFinal" => "408" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11846609" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0445" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "I.S. Young" 1 => "E.R. Trimble" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/000456329102800514" "Revista" => array:7 [ "tituloSerie" => "Ann Clin Biochem" "fecha" => "1991" "volumen" => "28" "numero" => "Pt 5" "paginaInicial" => "504" "paginaFinal" => "508" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1958055" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0450" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changes in nitric oxide level and superoxide dismutase activity during antimanic treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.S. Gergerlioglu" 1 => "H.A. Savas" 2 => "F. Bulbul" 3 => "S. Selek" 4 => "UE" 5 => "M. Yumru" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pnpbp.2006.12.020" "Revista" => array:7 [ "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry" "fecha" => "2007" "volumen" => "31" "numero" => "3" "paginaInicial" => "697" "paginaFinal" => "702" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17303295" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0455" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oxidative stress in early stage Bipolar Disorder and the association with response to lithium" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.T. de Sousa" 1 => "C.A. Zarate Jr." 2 => "M.V. Zanetti" 3 => "A.C. Costa" 4 => "L.L. Talib" 5 => "W.F. Gattaz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jpsychires.2013.11.011" "Revista" => array:6 [ "tituloSerie" => "J Psychiatr Res" "fecha" => "2014" "volumen" => "50" "paginaInicial" => "36" "paginaFinal" => "41" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24332923" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0460" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Specific subcellular changes in oxidative stress in prefrontal cortex from patients with bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.C. Andreazza" 1 => "J.F. Wang" 2 => "F. Salmasi" 3 => "L. Shao" 4 => "L.T. Young" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jnc.12316" "Revista" => array:7 [ "tituloSerie" => "J Neurochem" "fecha" => "2013" "volumen" => "127" "numero" => "4" "paginaInicial" => "552" "paginaFinal" => "561" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23692477" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0465" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decreased mRNA expression of uncoupling protein 2, a mitochondrial proton transporter, in post-mortem prefrontal cortex from patients with bipolar disorder and schizophrenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.D. Gigante" 1 => "A.C. Andreazza" 2 => "B. Lafer" 3 => "L.N. Yatham" 4 => "C.L. Beasley" 5 => "L.T. Young" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neulet.2011.09.064" "Revista" => array:7 [ "tituloSerie" => "Neurosci Lett" "fecha" => "2011" "volumen" => "505" "numero" => "1" "paginaInicial" => "47" "paginaFinal" => "51" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22001364" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0470" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.W. Gawryluk" 1 => "J.F. Wang" 2 => "A.C. Andreazza" 3 => "L. Shao" 4 => "L.T. Young" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1017/S1461145710000805" "Revista" => array:7 [ "tituloSerie" => "Int J Neuropsychopharmacol" "fecha" => "2011" "volumen" => "14" "numero" => "1" "paginaInicial" => "123" "paginaFinal" => "130" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20633320" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0475" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.C. Andreazza" 1 => "F. Kapczinski" 2 => "M. Kauer-Sant’Anna" 3 => "J.C. Walz" 4 => "D.J. Bond" 5 => "C.A. Goncalves" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Psychiatry Neurosci" "fecha" => "2009" "volumen" => "34" "numero" => "4" "paginaInicial" => "263" "paginaFinal" => "271" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19568477" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0480" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thiobarbituric acid reactive substances (TBARS) is a state biomarker of oxidative stress in bipolar patients in a manic phase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.C. Tsai" 1 => "T.L. Huang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jad.2014.10.045" "Revista" => array:6 [ "tituloSerie" => "J Affect Disord" "fecha" => "2015" "volumen" => "173" "paginaInicial" => "22" "paginaFinal" => "26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25462391" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0485" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Olanzapine protects PC12 cells from oxidative stress induced by hydrogen peroxide" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Z. Wei" 1 => "O. Bai" 2 => "J.S. Richardson" 3 => "D.D. Mousseau" 4 => "X.M. Li" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jnr.10668" "Revista" => array:7 [ "tituloSerie" => "J Neurosci Res" "fecha" => "2003" "volumen" => "73" "numero" => "3" "paginaInicial" => "364" "paginaFinal" => "368" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12868070" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0490" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Gubert" 1 => "L. Stertz" 2 => "B. Pfaffenseller" 3 => "B.S. Panizzutti" 4 => "G.T. Rezin" 5 => "R. Massuda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jpsychires.2013.06.018" "Revista" => array:7 [ "tituloSerie" => "J Psychiatr Res" "fecha" => "2013" "volumen" => "47" "numero" => "10" "paginaInicial" => "1396" "paginaFinal" => "1402" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23870796" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0495" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peripheral oxidative damage in early-stage mood disorders: a nested population-based case-control study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.V. Magalhaes" 1 => "K. Jansen" 2 => "R.T. Pinheiro" 3 => "G.D. Colpo" 4 => "L.L. da Motta" 5 => "F. Klamt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1017/S1461145711001532" "Revista" => array:7 [ "tituloSerie" => "Int J Neuropsychopharmacol" "fecha" => "2012" "volumen" => "15" "numero" => "8" "paginaInicial" => "1043" "paginaFinal" => "1050" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22008234" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0500" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of mood stabilizers on DNA damage in an animal model of mania" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.C. Andreazza" 1 => "M. Kauer-Sant’Anna" 2 => "B.N. Frey" 3 => "L. Stertz" 4 => "C. Zanotto" 5 => "L. Ribeiro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Psychiatry Neurosci" "fecha" => "2008" "volumen" => "33" "numero" => "6" "paginaInicial" => "516" "paginaFinal" => "524" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18982174" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0505" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.N. Frey" 1 => "S.S. Valvassori" 2 => "G.Z. Reus" 3 => "M.R. Martins" 4 => "F.C. Petronilho" 5 => "K. Bardini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Psychiatry Neurosci" "fecha" => "2006" "volumen" => "31" "numero" => "5" "paginaInicial" => "326" "paginaFinal" => "332" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16951735" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0510" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mood stabilizer lithium inhibits amphetamine-increased 4-hydroxynonenal-protein adducts in rat frontal cortex" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Tan" 1 => "L.T. Young" 2 => "L. Shao" 3 => "Y. Che" 4 => "W.G. Honer" 5 => "J.F. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1017/S1461145711001416" "Revista" => array:8 [ "tituloSerie" => "Int J Neuropsychopharmacol" "fecha" => "2012" "volumen" => "15" "numero" => "9" "paginaInicial" => "1275" "paginaFinal" => "1285" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21939588" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0211139X14002509" "estado" => "S300" "issn" => "0211139X" ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0515" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of lithium therapy on Na+-K+-ATPase activity and lipid peroxidation in bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "U. Banerjee" 1 => "A. Dasgupta" 2 => "J.K. Rout" 3 => "O.P. Singh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pnpbp.2011.12.006" "Revista" => array:7 [ "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry" "fecha" => "2012" "volumen" => "37" "numero" => "1" "paginaInicial" => "56" "paginaFinal" => "61" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22230647" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0520" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased oxidative stress and DNA damage in bipolar disorder: a twin-case report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.N. Frey" 1 => "A.C. Andreazza" 2 => "M. Kunz" 3 => "F.A. Gomes" 4 => "J. Quevedo" 5 => "M. Salvador" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pnpbp.2006.06.011" "Revista" => array:7 [ "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry" "fecha" => "2007" "volumen" => "31" "numero" => "1" "paginaInicial" => "283" "paginaFinal" => "285" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16859818" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0525" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A combined analysis of worldwide studies demonstrates an association between bipolar disorder and tobacco smoking behaviors in adults" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.G. Jackson" 1 => "F.J. Diaz" 2 => "L. Lopez" 3 => "J. de Leon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bdi.12319" "Revista" => array:6 [ "tituloSerie" => "Bipolar Disord" "fecha" => "2015" "volumen" => "17" "paginaInicial" => "575" "paginaFinal" => "597" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26238269" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0530" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mitochondria as a possible target for nicotine action" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Dominika" 1 => "R.W. Mariusz" 2 => "M. Bernadeta" 3 => "D. Karolina" 4 => "P. Monika" 5 => "P.K. Paulina" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10863-019-09800-z" "Revista" => array:7 [ "tituloSerie" => "J Bioenerg Biomembr" "fecha" => "2019" "volumen" => "51" "numero" => "4" "paginaInicial" => "259" "paginaFinal" => "276" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31197632" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02136163/0000003400000004/v1_202010090651/S0213616320300690/v1_202010090651/en/main.assets" "Apartado" => array:4 [ "identificador" => "64426" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/02136163/0000003400000004/v1_202010090651/S0213616320300690/v1_202010090651/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213616320300690?idApp=UINPBA00004N"]

Statistics

Original article

E. Kahyaci Kiliça,

Corresponding author

scully706@gmail.com

Corresponding author at: Uzunköprü State Hospital Psychiatry Department, Edirne, 22030, Turkey.

, R. Köse Çinarb, Y. Görgülüb, M.B. Sönmezb

a MD, Uzunköprü State Hospital Psychiatry Department, Edirne, 22030, Turkey

b Associate Professor, MD, Trakya University, School of Medicine, Department of Psychiatry, Edirne, 22030, Turkey

Read

1521

Times
was read the article

268

Total PDF

1253

Total HTML

Share statistics

 array:22 [
  "pii" => "S0213616320300690"
  "issn" => "02136163"
  "doi" => "10.1016/j.ejpsy.2020.08.001"
  "estado" => "S300"
  "fechaPublicacion" => "2020-10-01"
  "aid" => "112"
  "copyright" => "Asociaci&#243;n Universitaria de Zaragoza para el Progreso de la Psiquiatr&#237;a y la Salud Mental"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "Eur J Psychiatry. 2020;34:181-8"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S0213616320300598"
    "issn" => "02136163"
    "doi" => "10.1016/j.ejpsy.2020.06.003"
    "estado" => "S300"
    "fechaPublicacion" => "2020-10-01"
    "aid" => "105"
    "copyright" => "Asociaci&#243;n Universitaria de Zaragoza para el Progreso de la Psiquiatr&#237;a y la Salud Mental"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Eur J Psychiatry. 2020;34:189-94"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Validity and reliability of a Spanish version of the Standardised Assessment of Personality-Abbreviated Scale &#40;SAPAS&#41; for personality disorder screening in community mental health settings"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "189"
          "paginaFinal" => "194"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1508
              "Ancho" => 1528
              "Tamanyo" => 51030
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0075"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The area under the curve&#44; sensitivity&#44; and false positives for the different cut-off points for the SAPAS score&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "J&#46;E&#46; Mu&#241;oz-Negro, R&#46; G&#243;mez Passalacqua, N&#46; Pumar Alonso, J&#46;A&#46; Cervilla"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "J&#46;E&#46;"
              "apellidos" => "Mu&#241;oz-Negro"
            ]
            1 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "G&#243;mez Passalacqua"
            ]
            2 => array:2 [
              "nombre" => "N&#46;"
              "apellidos" => "Pumar Alonso"
            ]
            3 => array:2 [
              "nombre" => "J&#46;A&#46;"
              "apellidos" => "Cervilla"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213616320300598?idApp=UINPBA00004N"
    "url" => "/02136163/0000003400000004/v1_202010090651/S0213616320300598/v1_202010090651/en/main.assets"
  ]
  "en" => array:18 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Increased mitochondrial and cytosolic antioxidant enzymes in manic episodes"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "181"
        "paginaFinal" => "188"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "E&#46; Kahyaci Kili&#231;, R&#46; K&#246;se &#199;inar, Y&#46; G&#246;rg&#252;l&#252;, M&#46;B&#46; S&#246;nmez"
        "autores" => array:4 [
          0 => array:4 [
            "nombre" => "E&#46; Kahyaci"
            "apellidos" => "Kili&#231;"
            "email" => array:1 [
              0 => "scully706@gmail.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "R&#46; K&#246;se"
            "apellidos" => "&#199;inar"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Y&#46;"
            "apellidos" => "G&#246;rg&#252;l&#252;"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "M&#46;B&#46;"
            "apellidos" => "S&#246;nmez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "MD&#44; Uzunk&#246;pr&#252; State Hospital Psychiatry Department&#44; Edirne&#44; 22030&#44; Turkey"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Associate Professor&#44; MD&#44; Trakya University&#44; School of Medicine&#44; Department of Psychiatry&#44; Edirne&#44; 22030&#44; Turkey"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author at&#58; Uzunk&#246;pr&#252; State Hospital Psychiatry Department&#44; Edirne&#44; 22030&#44; Turkey&#46;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1191
            "Ancho" => 2065
            "Tamanyo" => 75894
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Gene expression levels of antioxidant enzymes&#44; mean of 2<span class="elsevierStyleSup">&#8722;&#916;&#916;Ct</span>&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">CAT&#44; catalase&#59; GPx&#44; glutathione peroxidase&#59; GS&#44; glutathione synthetase&#59; SOD1&#44; SOD2&#44; superoxide dismutase 1&#44; 2&#46; &#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#44; &#42;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bipolar disorder &#40;BD&#41; is a chronic disease that consists of repeating mania and depression episodes&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">1</span></a> There is increasing evidence from recent studies about the role of oxidative stress in the etiology of BD&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">2&#8211;6</span></a> These studies about oxidative stress in BD have also been intensified concerning the activities of antioxidant enzymes and the measurement of the lipid peroxidation end-products&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Oxidative stress has been started to be defined as a disruption of redox signaling and control&#44; despite it was previously described in terms of a balance between pro-oxidants and antioxidants&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">8</span></a> As major components of oxidative stress&#44; free radicals grow out in all of the tissues of the body during primarily oxidative phosphorylation in the mitochondria&#46; Reactive oxygen species &#40;ROS&#41; are typically synthesized as a by-product of cellular respiration in the electron transport chain&#46; If electrons are released from complexes of the transport chain prematurely&#44; they transform molecular oxygen into superoxide radicals&#44; and as a result of this biochemical reaction&#44; various reactive oxygen species get synthesized&#46; Enzymes like superoxide dysmutase &#40;SOD&#41;&#44; glutathione peroxidase &#40;GPx&#41; and catalase &#40;CAT&#41; have the ability to save the cells from oxidative injury&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Oxidative stress has been suggested to have an important role in BD pathophysiology recently&#46; Some studies report increased peripheral markers of oxidative stress in BD and some studies report changes in the levels of antioxidant enzymes and increased lipid peroxidation end-products&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">5&#44;11&#8211;14</span></a> Significant increases in antioxidant enzymes&#44; DNA damage&#44; protein carbonyl ingredients attributable to oxidative stress&#44; increases in lipid peroxidation end products and nitric oxide levels were detected in some other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">2&#44;14&#8211;16</span></a> However&#44; the results of these studies are contradictory&#46; Cytosolic SOD activity was found to be high in an acute episode of BD dissimilar to a euthymic phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">11&#44;13</span></a> Similarly&#44; increases were reported in cytosolic SOD activity in patients during manic episodes that were not treated&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">17</span></a> However&#44; other studies did not find any differences between the SOD activities of the patient group and that of the healthy control group&#59; also&#44; some other research showed decreases in the cytosolic SOD activity in BD&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">18&#44;19</span></a> Nevertheless&#44; most studies have reported an increase in antioxidant enzyme levels&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">There are clinical studies that showed that mood stabilizers decrease oxidative stress markers in peripheral samples&#46; These studies proved the therapeutic effects of mood stabilizer treatments that show antioxidant properties&#46; Evidences show that present mood stabilizer treatments have neuroprotective effects against oxidative stress by arranging various antioxidant pathways in the cell&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">4&#44;17&#44;20&#8211;22</span></a> Another aspect of the role of oxidative stress in BD is the fact that antioxidant compounds like N-acetylcystein &#40;NAC&#41; have been shown to be beneficial in BD treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">23&#8211;27</span></a> The typical antipsychotics have been found to reduce the antioxidants and increase the oxidants&#59; in contrast&#44; the atypical antipsychotics have been found to increase the antioxidants and reduce the oxidants&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">28&#8211;32</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The studies about oxidative stress in BD have investigated the serum antioxidant levels till today&#46; Conflicting results showing different serum enzyme levels have been reported&#46; This may be a result of the variable production of enzymes under influence of numerous factors&#46; Thus&#44; the serum levels of these enzymes may not be showing the real tendency in BD on antioxidant enzyme production&#46; According to a literature search&#44; no previous human studies have examined the peripheral blood antioxidant gene expression&#46; We hypothesized that the gene expression of the antioxidant enzymes and plasma malondialdehyde &#40;MDA&#41; levels that show lipid peroxidation will be altered in BD patients&#46; In this study&#44; the mRNA expressions of cytosolic and mitochondrial superoxide dismutase &#40;SOD1&#44; SOD2&#41;&#44; catalase &#40;CAT&#41;&#44; glutathione synthetase &#40;GS&#41;&#44; glutathione peroxidase &#40;GPx&#41; were examined in the peripheral blood of adult&#44; drug-free BD patients during manic and remission periods and a healthy control group&#46; We selected the studied possible biomarkers focusing on evidence based on findings in peripheral blood&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">2&#44;11&#44;12&#44;14&#8211;16&#44;33</span></a> Despite the fact that studies about oxidative stress have not yet explained the pathophysiology of BD&#44; these investigations could resolve this issue by finding markers specific to the disorder that can be searched in blood samples and following the response to treatment with biological markers&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">This study included 20 medication-free patients aged 18&#8211;65 years who had been diagnosed with BD-I in the past and who were currently experiencing an acute manic episode&#46; Other inclusion criteria for the patient and control groups were as follows&#58; having a body mass index &#40;BMI&#41; within a normal range &#40;18&#46;5&#8211;25<span class="elsevierStyleHsp" style=""></span>kg&#47;m2&#41;&#44; having a diet similar to that of the other participants &#40;i&#46;e&#46; rich in carbohydrates&#41; and not performing physical exercise&#46; All the patients and healthy controls stated that they were not on a special diet and did not participate in strenuous exercise activity&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Exclusion criteria for the patient and the control groups were as follows&#58; alcohol and substance &#40;except nicotine&#41; abuse or dependence&#44; the presence of systemic diseases &#40;including cardiovascular and endocrine diseases&#41;&#44; usage of any antioxidant agents &#40;e&#46;g&#46; vitamins E&#44; C and NAC&#41;&#44; the presence of epilepsy or severe neurological disorders and the presence of infectious diseases&#46; For both medical and neurological diseases&#44; exclusion was based on the results of general medical&#44; neurological examinations and routine laboratory results&#46; Patients who used psychotropic drugs were also excluded&#46; Purification periods for psychotropic drugs were two weeks for oral drugs and one month for parenteral drugs&#59; for participants who used mood stabilizer drugs&#44; their blood levels had to be 0&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The control group consisted of 20 medication-free&#44; healthy volunteers who had no current&#44; past or first-degree family history of a major psychiatric disorder&#46; The participants were matched for age&#44; gender&#44; smoking&#44; dietary and exercising habits&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">This study was performed at the Medical Faculty of Trakya University from October 2014 to April 2015&#46; A semi-structured form was used to detect several socio-demographic data and clinical variables&#46; The diagnosis of BD was carried out using the Structured Clinical Interview for DSM-IV-Axis I &#40;SCID-I&#41;&#46; The patients had to fulfill criteria for manic episodes according to the Diagnostic and Statistical Manual of Mental Disorders&#44; Fifth Edition &#40;DSM-5&#41;&#46; Symptoms were assessed using the Young Mania Rating Scale &#40;YMRS&#41; and the Hamilton Depression Rating Scale &#40;HDRS&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Approval of this research was given by the ethics committee of the Medical Faculty of Trakya University&#46; All patients or family members were given a written informed consent form before entering the study&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Laboratory data</span><p id="par0055" class="elsevierStylePara elsevierViewall">Blood samples were obtained using vacutainer tubes from the patients and the controls between 08&#58;00 and 10&#58;00 a&#46;m&#46;&#44; and the samples were centrifuged at 3000<span class="elsevierStyleHsp" style=""></span>rpm for 15<span class="elsevierStyleHsp" style=""></span>min and stored at &#8722;80&#176; C for further analysis&#46; The samples from the patients were taken the day after their admittance to the inpatient clinic&#46; Blood samples were taken again when the patients fulfilled the remission criteria as defined by their total score on the YMRS of &#60;4&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Determination of gene expression levels</span><p id="par0060" class="elsevierStylePara elsevierViewall">The mRNA expression levels were measured using the quantitative real-time polymerase chain reaction &#40;qRT-PCR&#41;&#46; The total RNA was isolated from the whole blood using the PureLink&#174; RNA Mini Kit &#40;Life Technologies&#44; USA&#41; according to the manufacturer&#39;s instructions&#46; The extracted RNA concentrations were measured by the Qubit&#174; Fluorometer &#40;Life Technologies&#44; USA&#41;&#46; The first strand of cDNA was synthesized using a High Capacity cDNA Reverse Transcription Kit &#40;Life Technologies&#44; USA&#41;&#46; The c DNA synthesis was performed using a thermal cycler Applied Biosystems&#174; Veriti&#174;&#46; The gene expression levels of the antioxidant enzymes were analyzed by qRT-PCR using the SYBR&#174; Select Master Mix &#40;Life Technologies&#44; USA&#41; on an ABI Step One Plus Real-Time PCR system&#46; PCR Cycling&#58; 2<span class="elsevierStyleHsp" style=""></span>min at 50<span class="elsevierStyleHsp" style=""></span>&#176;C and 10<span class="elsevierStyleHsp" style=""></span>min at 95<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 40 cycles at 95<span class="elsevierStyleHsp" style=""></span>&#176;C for 15<span class="elsevierStyleHsp" style=""></span>s&#44; and 60<span class="elsevierStyleHsp" style=""></span>&#176;C for 60<span class="elsevierStyleHsp" style=""></span>s&#46; Glyceraldehydes 3-phosphate dehydrogenase &#40;GADPH&#41; &#91;Forward &#40;5&#8242;-AATTCCGATCTTCGACATGG3-&#8242;&#41; Reverse &#40;5&#8242;-GAAAAAGCGGCAGTCGTAAT-3&#8242;&#41;&#93; was used as the housekeeping gene&#46; The primers used in the gene expression are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The comparative cycle threshold &#40;2<span class="elsevierStyleSup">&#8722;&#916;&#916;Ct</span>&#41; method was used for the gene expression analysis of data measured by PCR&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">35</span></a> Ct &#40;threshold cycle&#41; indicated the fractional cycle number at which the amount of amplified target reached a fixed threshold&#46; &#916;Ct corresponded to normalized Ct values and was equal to the difference in cycle thresholds between the target &#40;gene expressions of predetermined molecules&#41; and reference genes &#40;housekeeping genes&#41;&#46; GAPDH was used as the housekeeping gene in our research&#46; &#916;&#916;Ct corresponded to the difference between the expression level of the average &#916;Ct of the patient group and that of the control group&#46; 2<span class="elsevierStyleSup">&#8722;&#916;&#916;Ct</span> denoted the fold change in the expression level change of the following measures of the patient group compared to the control group&#46; All analyses were performed in the same laboratory&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Determination of plasma MDA levels</span><p id="par0065" class="elsevierStylePara elsevierViewall">Lipid peroxidation levels were determined by measuring the end product of lipid peroxidation MDA&#46; Plasma MDA values were calculated using the extinction coefficient of the MDA-thiobarbituric acid complex at 532<span class="elsevierStyleHsp" style=""></span>nm&#46; Levels of plasma MDA were measured by the thiobarbituric acid &#40;TBA&#41; method&#44; which was modified from Young et al&#46;&#8217;s<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">36</span></a> method&#46; Peroxidation was measured as the production of MDA&#44; which in combination with TBA forms a pink chromogen compound whose absorbance at 532<span class="elsevierStyleHsp" style=""></span>nm was measured&#46; The MDA results were expressed as nmol&#47;ml&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Statistical analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">Data were analyzed using the SPSS 20&#46;0 version for Windows statistical software&#46; The Kolmogrov&#8211;Smirnov test was used to compare the observed cumulative distribution functions&#59; our sample presented abnormal distribution&#46; Non-parametric statistical methods were used to analyze the data&#44; and groups were compared using Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> and Wilcoxon tests&#46; Categorical variables were analyzed with a chi-square test&#44; and the relationship between the biochemical and clinical variables was assessed using spearman correlation&#46; The results were expressed as the means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41;&#46; A <span class="elsevierStyleItalic">p</span> value of less than 0&#46;05 was used to indicate statistical significance&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Demographics</span><p id="par0075" class="elsevierStylePara elsevierViewall">Twenty inpatients with BD in a manic episode &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41; and healthy volunteers &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41; were included in this study&#46; None of the subjects in either group had comorbid diseases&#46; The mean ages of the patient and control groups were similar &#40;31&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;23 and 31&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;31&#44; respectively&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;968&#41;&#46; Each group was composed of 14 males and 6 females&#46; The average BMI of the patients and controls was within the normal range &#40;24&#46;3<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#44; 24&#46;7<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;0<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; and was similar between the two groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;669&#41;&#46; In the patient group&#44; the time to reach remission was 9&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5 weeks&#46; The clinical characteristics of the BD patients and the drugs used during remission are included in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Comparison of mania and controls</span><p id="par0080" class="elsevierStylePara elsevierViewall">The bipolar patients in a manic phase had higher mean gene expression levels of SOD2&#44; CAT&#44; GPx and GS than the healthy subjects&#46; The gene expression levels of SOD1 showed no significant difference between the two groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The gene expression levels of antioxidant enzymes had no significant association with the YMRS scores &#40;for CAT&#44; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;360&#59; for GPx&#44; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;230&#59; for GS&#44; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;231&#59; for SOD1&#44; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;064&#59; for SOD2&#44; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;241&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; The plasma levels of MDA showed no significant difference between the two groups &#40;manic group<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;113<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;180<span class="elsevierStyleHsp" style=""></span>nmol&#47;ml&#44; control group<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;064<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;023<span class="elsevierStyleHsp" style=""></span>nmol&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;935&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Comparison of mania and remission</span><p id="par0085" class="elsevierStylePara elsevierViewall">Twenty bipolar inpatients received follow-up appointments&#44; in which the gene expression levels of their antioxidant enzymes and the plasma levels of their MDA were measured after treatment&#46; The patients&#8217; &#40;16 men and 4 women&#41; mean hospitalization duration was 36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;82 days&#46; The YMRS scores at baseline were 30&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;33&#44; and 2&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;11 at the end point&#46; We found significantly decreased changes in the expression levels of GPx in bipolar patients who had received treatment &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#44; while other markers &#40;SOD1&#44;2&#44; CAT&#44; GPx&#44; GS&#41; showed no significant changes after treatment &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The plasma levels of MDA at baseline were 0&#46;113<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;180<span class="elsevierStyleHsp" style=""></span>nmol&#47;ml and 0&#46;073<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;030<span class="elsevierStyleHsp" style=""></span>nmol&#47;ml at the end point&#44; showing no significant change after treatment &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;654&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The most important finding in this study is that bipolar patients in a manic phase had significantly higher gene expression levels of SOD2&#44; CAT&#44; GPx and GS than the healthy controls&#46; The expression levels of GPx mRNA decreased during the remission period compared to the levels in the manic state&#46; It can be supposed that this dissimilarity formed as a compensating mechanism against the oxidative stress that increases during a manic episode&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Conflicting results were detected in clinical studies that investigated antioxidant enzyme levels in BD&#46; Different and conflicting data in the literature could be a result of racial differences&#44; diet properties&#44; lifestyles that influence oxidative stress&#44; differences between disease episodes&#44; treatment differences and procedures used in studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">12&#44;14&#44;18</span></a> Regarding the studies comparing patients with BD in a manic episode and healthy subjects&#44; some show no increase&#44; some show a decrease and others show no change in serum or erythrocyte SOD activities at all&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">11&#44;13&#44;17&#44;37</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Detecting no difference between the SOD activities of patient groups and healthy subjects&#44; despite expectations that those of the patient groups would increase&#44; can be interpreted as an indication that the changes at transcriptional levels were not actualized at the protein level&#46; Since there is no data about differences between the gene expression levels of these enzymes in BD&#44; in the current study&#44; we aimed to investigate the SOD1 and SOD2 gene expression levels in order to fill this empty space in the literature&#46; There are studies in which cytosolic SOD levels were detected in BD patients that were similar to that of the control group&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">4&#44;38</span></a> There were no significantly important differences between the SOD2 levels in a study in which postmortem prefrontal cortex samples of BD patients&#44; schizophrenia patients and healthy subjects were evaluated&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">39</span></a> Furthermore&#44; there were no differences between the SOD1 and SOD2 levels of the postmortem dorsolateral prefrontal cortex cross-sections from BD patients&#44; schizophrenia patients and healthy subjects&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">40</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In most of the studies&#44; SOD enzyme levels were not evaluated separately as cytosolic or mitochondrial&#46; In our study&#44; it was discovered that mitochondrial SOD gene enzyme levels were higher in manic patients than in healthy subjects&#46; There were no statistically significant differences in cytosolic SOD levels between the two groups&#46; The increase that was detected in the mitochondrial SOD expression level&#44; which is the first antecedent of antioxidant defence&#44; shows that oxidative stress may be increasing during the acute episode of the disease&#59; antioxidant enzymes prevented this from happening in our study&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Increases were detected in the CAT gene expression levels during manic episodes compared to the controls in our study&#46; This increase can be interpreted as a compensating response that is promoted synchronously with the increase in SOD expression that grows as the first defence step against oxidative stress&#46; Some studies showed that there were increases or decreases in serum CAT levels during BD manic episodes&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">11&#44;14&#44;17&#44;19&#44;38</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The GPx expression levels were higher in manic patients when compared to the controls&#46; This increased levels may have a relation with increased expression of mitochondrial SOD that removes H2O2&#46; A positive correlation was found between gene expression levels of SOD2 and GPx&#46; Variable results were found in studies investigating GPx activity&#46; For example&#44; GPx activity was found significantly high during euthymic phase by Andreazza et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">11</span></a> GPx levels were also found significantly higher in BD patients during depressive phase when compared to the controls&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">38</span></a> However&#44; some studies found unchanged GPx activity between BP patients and healthy controls&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">12&#44;14&#44;41</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The significant increase in GS expression levels in the manic patients when compared to the control group may be due to the fact that glutathione synthesis plays an important role in the defence mechanism&#44; which is composed of antioxidant enzymes against oxidative stress&#46; Also&#44; some studies show decreases in the glutathione levels of BD&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">19&#44;41</span></a> When BD patients in early or late stages were compared with each other in order to evaluate the effect of BD duration on antioxidant enzymes&#44; there were no significant differences between the two groups regarding the gene expression levels of their antioxidant enzymes&#46; However&#44; an increase in antioxidant enzymes during the late stage was detected in antioxidant enzymes&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">42</span></a> This difference between this study and our study could be a result of the shorter disease duration of the sample that composes our study&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In the current study&#44; the antioxidant gene expression levels of the patients who were in manic episode and subsequent remission phase were found to be similar except for GPx&#46; No differences were detected between the SOD&#44; CAT and GPx levels before and after treatment in the patient group&#44;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">43</span></a> the fact that there were no differences in our study either could be interpreted as a result of continuing oxidative stress during a remission phase and continuing the compensatory response at the level of gene expression&#46; In contrast&#44; the CAT&#44; GPx and MDA levels were found to show significant change after mood stabilizer treatment in BD patients&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">4</span></a> Also&#44; their TBARS and SOD levels decreased significantly after six months of lithium treatment for BD patients during depressive episodes&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">38</span></a> In our study&#44; patients were on different antipsychotic drugs&#44; in addition to lithium and valproate&#46; It was discovered that typical antipsychotics were increasing oxidants and decreasing antioxidants&#59; conversely&#44; atypical antipsychotics were decreasing oxidants and increasing antioxidants&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">28&#44;30&#44;31&#44;44</span></a> Ninety-five percent of the manic patients in our study were on atypical antipsychotic treatment&#59; from the results&#44; it can be supposed that atypical antipsychotic drugs had a mixed effect on their gene expression level changes during their remission phase&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">We found similar levels of plasma MDA between patient and control groups in our study&#46; Our findings are discordant with the results of the meta-analysis&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">9</span></a> which found that thiobarbituric acid reactive substances &#40;TBARS&#41; increase in BD&#46; However&#44; some recent studies did not find any difference between the TBARS levels in BD like our study did&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">14&#44;45&#44;46</span></a> Plasma TBARS levels were found to be similar to that of the control group in BD type I and type II&#44; this similarity was explained by the simultaneous CAT and GPx increase&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">38</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The plasma MDA levels of manic episode patients that have gone into remission after mood stabilizer treatment were detected as similar to their levels before treatment in our study&#46; Mood stabilizer drugs that were given to patients in various studies were reported to produce some effects that helped decrease oxidative lipid damage&#46; In the studies that were done with rat models&#44; in which mania episodes were induced by amphetamine&#44; lithium treatment was reported to decrease lipid peroxidation&#46;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">47&#8211;49</span></a> Clinical studies have been shown to reduce the plasma TBARS levels of lithium treatment in BD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">17&#44;38&#44;50&#44;51</span></a> The effect of only mood stabilizer treatment on oxidative lipid damage was considered in the inspected studies&#44; but various antipsychotic treatments were given to patients for treatment of manic episodes&#46; This situation may have had an effect on the MDA levels that were measured during remission episodes&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Bipolar patients are known to have higher rates of smoking than the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">52</span></a> Nicotine exposure was shown to increase cytosolic ROS levels and leads to oxidative stress in numerous studies on cultured cells&#46; The levels and activities of antioxidant enzymes such as SOD&#44; CAT&#44; GR and GPx were reported to decrease following nicotine exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">53</span></a> The subjects with substance abuse and dependence were excluded in our BD and control groups but the subjects with nicotine abuse and dependence were not excluded&#46; Nearly all of our manic patients &#40;80&#37;&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41; and controls &#40;70&#37;&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; were smokers&#46; Therefore&#44; the effects of smoking on oxidative stress molecules were not ruled out in our study&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Our study has some limitations&#58; First&#44; only the manic episodes of BD were investigated&#46; Also&#44; this research used a small sample size&#44; and obtained information regarding the patients&#8217; diet and exercise habits based on subjective self-reports&#46; Additionally&#44; another limitation was the variability of the antipsychotic treatments given to our manic episode patient group and the inability of excluding the drug&#39;s effects&#46; We analyzed mood stabilizing drug blood levels before enrolling the participants into the study&#46; However&#44; analysing antipsychotic drug blood levels were impossible due to laboratory limitations&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Since there is no data about the differences between the gene expression levels of the enzymes in BD&#44; we aimed to investigate the SOD1 and SOD2 gene expression levels in order to fill this empty space in the literature&#46; A strong point of our research is the study population&#44; since it comprised BD patients with severe mania and no psychotropic drug use&#46; Also&#44; it involved the subsequent remission period of the same patients and healthy controls&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0155" class="elsevierStylePara elsevierViewall">Detection of increases in CAT&#44; GPx&#44; GS and SOD2 in the gene expression levels during a manic episode may be due to the activation of antioxidant systems against oxidative stress that increases in patients&#46; Research shows that oxidative stress plays an important role in BD pathophysiology&#44; and the drugs that decrease oxidative stress can give hope for future treatment modalities of BD&#46; Further research needs to be conducted in bigger samples than ours concerning antioxidant gene expression in all episodes of BD with gene expressions&#46; Investigation of these differences in groups in which disorder did not yet arise&#44; but of higher risk for BD and additional research specifically about mitochondrial SOD&#44; GS&#44; GPx and CAT enzymes could provide further information about the role of the differences in BD etiopathogenesis&#59; as a result&#44; newer diagnosis&#44; treatment and follow-up options could be developed&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; this is the first study in the field of psychiatry to show gene expression changes in oxidative stress biomarkers of BD patients and treatment-related changes in the levels of these biomarkers&#46; Follow-up appointments with the same patient group will be needed in order to verify these findings&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Ethical considerations</span><p id="par0165" class="elsevierStylePara elsevierViewall">This study was approved by the local ethics committee of the Trakya University Faculty of Medicine &#40;Project No&#46; 2014&#47;113&#41;&#46; All procedures followed were in accordance with The Code of Ethics of the World Medical Association and with the Helsinki Declaration&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0170" class="elsevierStylePara elsevierViewall">This study was supported by grant form the Scientific Research Projects Unit of the Trakya University&#44; Edirne&#44; Turkey &#40;Project No&#46;&#58; 2014&#47;100&#41;&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres1396223"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Background and objectives"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusion"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1279408"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patients"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Laboratory data"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Determination of gene expression levels"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Determination of plasma MDA levels"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Results"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Demographics"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Comparison of mania and controls"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Comparison of mania and remission"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Discussion"
        ]
        6 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conclusions"
        ]
        7 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Ethical considerations"
        ]
        8 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conflict of interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-12-09"
    "fechaAceptado" => "2020-08-10"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1279408"
          "palabras" => array:5 [
            0 => "Bipolar disorder"
            1 => "Oxidative stress"
            2 => "Malondialdehyde"
            3 => "Antioxidant enzymes"
            4 => "Gene expression"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">An increasing number of studies have been conducted to investigate the role of oxidative stress in the pathophysiology of bipolar disorder &#40;BD&#41;&#46; The aim of our study was to detect the levels of plasma malondialdehyde and the gene expression of antioxidant enzymes in BD patients during manic period and to assess the changes of these markers during the subsequent remission period&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This study involved 20 drug-free&#44; hospitalized patients with BD type I who met the manic episode diagnostic criteria according to DSM-5&#44; as well as 20 age-sex matched healthy controls&#46; As a marker of lipid damage&#44; malondialdehyde plasma levels were measured by the thiobarbituric acid method&#59; mRNA expression levels of catalase &#40;CAT&#41;&#44; glutathione peroxidase &#40;GPx&#41;&#44; glutathione synthetase &#40;GS&#41;&#44; superoxide dismutase &#40;SOD1&#41; and mitochondrial superoxide dismutase &#40;SOD2&#41; were measured by real-time quantitative PCR from peripheral whole blood samples&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In a manic episode&#44; the expression levels of CAT&#44; GPx&#44; GS and SOD2 were higher in the patients than the healthy controls&#46; With treatment&#44; only the GPx levels decreased significantly&#46; The malondialdehyde and SOD1 levels did not differ between the patients and controls&#44; and in the patient group&#44; they did not differ between the mania and remission periods&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This is the first study that has assessed the mRNA expression levels of antioxidant enzymes in patients with BD type I&#46; The data from this study suggests that there is an increase in the expression of antioxidant enzymes as a response to oxidative stress in BD&#44; and that the gene expression levels of these antioxidant enzymes could be potential biomarkers for manic phase of the disorder&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1191
            "Ancho" => 2065
            "Tamanyo" => 75894
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Gene expression levels of antioxidant enzymes&#44; mean of 2<span class="elsevierStyleSup">&#8722;&#916;&#916;Ct</span>&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">CAT&#44; catalase&#59; GPx&#44; glutathione peroxidase&#59; GS&#44; glutathione synthetase&#59; SOD1&#44; SOD2&#44; superoxide dismutase 1&#44; 2&#46; &#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#44; &#42;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">SOD1&#44; SOD2&#44; superoxide dismutase 1&#44; 2&#59; CAT&#44; catalase&#59; GS&#44; glutathione synthetase&#59; GPx&#44; glutathione peroxidase&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SOD1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Forward &#40;5&#8242;-GTTCGGTGACAACACCAATG-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reverse &#40;5&#8242;-GGAGTCGGTGATGTTGACCT-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SOD2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Forward &#40;5&#8242;-TCTGAAGAAGGCCATCGAGT-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reverse &#40;5&#8242;-GCAGATAGTAGGCGTGCTCC-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CAT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Forward &#40;5&#8242;-TACGAGCAGGCCAAGAAGTT-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reverse &#40;5&#8242;-ACCTTGTACGGGCAGTTCAC-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Forward &#40;5&#8242;-TGGGACCAGCAAGTAAAACC-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reverse &#40;5&#8242;-TCGCGAATG TAGAACTCGTG-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GPx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Forward &#40;5&#8242;-TTCCCGTGCAACCAGTTTG-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reverse &#40;5&#8242;-TTCACCTCGCACTTCTCGAA-3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2396189.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Primers of antioxidant enzymes&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Values are given as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation or number &#40;&#37;&#41;&#46; BMI&#44; body mass index&#59; YMRS&#44; Young Mania Rating Scale&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;968&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gender &#40;male&#47;female&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Education&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;547&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Duration of illness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;40<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The number of manic episodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The number of depressive episodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospitalization number&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;669&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Current smoking &#40;yes&#47;no&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;716&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">YMRS at admission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">YMRS at the end of the study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psychotic features&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Drug use at the end of the study</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lithium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Valproat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Risperidone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ketiapine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Olanzapine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Aripiprazole&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Haloperidol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2396188.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Demographics and clinical characteristics of BD and control group&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">CAT&#44; catalase&#59; GPx&#44; glutathione peroxidase&#59; GS&#44; glutathione synthetase&#59; SOD1&#44; SOD2&#44; superoxide dismutase 1&#44; 2&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">The gene expression levels of controls are 1 &#40;according to 2<span class="elsevierStyleSup">&#8722;&#916;&#916;Ct</span> method&#41; and not represented in the table&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">p</span> values are calculated by using Mann&#8211;Whitney test&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients in manic phase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CAT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GPx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SOD1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SOD2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>sd&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>38&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>46&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Median&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;874&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;031&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;837&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">p</span> values&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;022&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&#42;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&#42;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;682&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&#42;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2396190.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Gene expression levels of antioxidant enzymes&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Median values are given in the table&#46; SOD1&#44; SOD2&#44; superoxide dismutase 1&#44; 2&#59; CAT&#44; catalase&#59; GS&#44; glutathione synthetase&#59; GPx&#44; glutathione peroxidase&#59; MDA&#44; malondialdehyde&#59; YMRS&#44; Young Mania Rating Scale&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CAT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GPx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SOD1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SOD2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MDA&#40;nmol&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">YMRS scores&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;874&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;031&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;837&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;061&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Endpoint&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;524&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;042&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;323&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;195&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;572&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;070&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;650&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;003<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;281&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;155&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;943&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;654&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2396191.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Changes in the gene expression levels of antioxidant enzymes and plasma MDA levels after teatment in bipolar patients&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:53 [
            0 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;H&#46; Belmaker"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra035354"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "351"
                        "numero" => "5"
                        "paginaInicial" => "476"
                        "paginaFinal" => "486"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15282355"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathways underlying neuroprogression in bipolar disorder&#58; focus on inflammation&#44; oxidative stress and neurotrophic factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Berk"
                            1 => "F&#46; Kapczinski"
                            2 => "A&#46;C&#46; Andreazza"
                            3 => "O&#46;M&#46; Dean"
                            4 => "F&#46; Giorlando"
                            5 => "M&#46; Maes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neubiorev.2010.10.001"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurosci Biobehav Rev"
                        "fecha" => "2011"
                        "volumen" => "35"
                        "numero" => "3"
                        "paginaInicial" => "804"
                        "paginaFinal" => "817"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20934453"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An updated meta-analysis of oxidative stress markers in bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "N&#46;C&#46; Brown"
                            1 => "A&#46;C&#46; Andreazza"
                            2 => "L&#46;T&#46; Young"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.psychres.2014.04.005"
                      "Revista" => array:7 [
                        "tituloSerie" => "Psychiatry Res"
                        "fecha" => "2014"
                        "volumen" => "218"
                        "numero" => "1&#8211;2"
                        "paginaInicial" => "61"
                        "paginaFinal" => "68"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24794031"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antioxidant enzyme activities and oxidative stress in affective disorders"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;E&#46; Ozcan"
                            1 => "M&#46; Gulec"
                            2 => "E&#46; Ozerol"
                            3 => "R&#46; Polat"
                            4 => "O&#46; Akyol"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00004850-200403000-00006"
                      "Revista" => array:7 [
                        "tituloSerie" => "Int Clin Psychopharmacol"
                        "fecha" => "2004"
                        "volumen" => "19"
                        "numero" => "2"
                        "paginaInicial" => "89"
                        "paginaFinal" => "95"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15076017"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of oxidative stress in the pathophysiology of bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;V&#46; Steckert"
                            1 => "S&#46;S&#46; Valvassori"
                            2 => "M&#46; Moretti"
                            3 => "F&#46; Dal-Pizzol"
                            4 => "J&#46; Quevedo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11064-010-0195-2"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurochem Res"
                        "fecha" => "2010"
                        "volumen" => "35"
                        "numero" => "9"
                        "paginaInicial" => "1295"
                        "paginaFinal" => "1301"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20499165"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;F&#46; Wang"
                            1 => "L&#46; Shao"
                            2 => "X&#46; Sun"
                            3 => "L&#46;T&#46; Young"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1399-5618.2009.00717.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Bipolar Disord"
                        "fecha" => "2009"
                        "volumen" => "11"
                        "numero" => "5"
                        "paginaInicial" => "523"
                        "paginaFinal" => "529"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19624391"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative stress in bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "V&#46; Tang"
                            1 => "J&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Biochem Anal Biochem"
                        "fecha" => "2012"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Redefining oxidative stress"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46;P&#46; Jones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1089/ars.2006.8.1865"
                      "Revista" => array:7 [
                        "tituloSerie" => "Antioxid Redox Signal"
                        "fecha" => "2006"
                        "volumen" => "8"
                        "numero" => "9-10"
                        "paginaInicial" => "1865"
                        "paginaFinal" => "1879"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16987039"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative stress markers in bipolar disorder&#58; a meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;C&#46; Andreazza"
                            1 => "M&#46; Kauer-Sant&#8217;Anna"
                            2 => "B&#46;N&#46; Frey"
                            3 => "D&#46;J&#46; Bond"
                            4 => "F&#46; Kapczinski"
                            5 => "L&#46;T&#46; Young"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jad.2008.04.013"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Affect Disord"
                        "fecha" => "2008"
                        "volumen" => "111"
                        "numero" => "2&#8211;3"
                        "paginaInicial" => "135"
                        "paginaFinal" => "144"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18539338"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peroxide detoxification by brain cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46; Dringen"
                            1 => "P&#46;G&#46; Pawlowski"
                            2 => "J&#46; Hirrlinger"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jnr.20280"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Neurosci Res"
                        "fecha" => "2005"
                        "volumen" => "79"
                        "numero" => "1&#8211;2"
                        "paginaInicial" => "157"
                        "paginaFinal" => "165"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15573410"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum S100B and antioxidant enzymes in bipolar patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;C&#46; Andreazza"
                            1 => "C&#46; Cassini"
                            2 => "A&#46;R&#46; Rosa"
                            3 => "M&#46;C&#46; Leite"
                            4 => "L&#46;M&#46; de Almeida"
                            5 => "P&#46; Nardin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jpsychires.2006.07.013"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Psychiatr Res"
                        "fecha" => "2007"
                        "volumen" => "41"
                        "numero" => "6"
                        "paginaInicial" => "523"
                        "paginaFinal" => "529"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16956621"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Kuloglu"
                            1 => "B&#46; Ustundag"
                            2 => "M&#46; Atmaca"
                            3 => "H&#46; Canatan"
                            4 => "A&#46;E&#46; Tezcan"
                            5 => "N&#46; Cinkilinc"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cbf.940"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cell Biochem Funct"
                        "fecha" => "2002"
                        "volumen" => "20"
                        "numero" => "2"
                        "paginaInicial" => "171"
                        "paginaFinal" => "175"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11979513"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Kunz"
                            1 => "C&#46;S&#46; Gama"
                            2 => "A&#46;C&#46; Andreazza"
                            3 => "M&#46; Salvador"
                            4 => "K&#46;M&#46; Cereser"
                            5 => "F&#46;A&#46; Gomes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pnpbp.2008.07.001"
                      "Revista" => array:7 [
                        "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry"
                        "fecha" => "2008"
                        "volumen" => "32"
                        "numero" => "7"
                        "paginaInicial" => "1677"
                        "paginaFinal" => "1681"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18657586"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;K&#46; Ranjekar"
                            1 => "A&#46; Hinge"
                            2 => "M&#46;V&#46; Hegde"
                            3 => "M&#46; Ghate"
                            4 => "A&#46; Kale"
                            5 => "S&#46; Sitasawad"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0165-1781(03)00220-8"
                      "Revista" => array:7 [
                        "tituloSerie" => "Psychiatry Res"
                        "fecha" => "2003"
                        "volumen" => "121"
                        "numero" => "2"
                        "paginaInicial" => "109"
                        "paginaFinal" => "122"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14656446"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "DNA damage in bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;C&#46; Andreazza"
                            1 => "B&#46;N&#46; Frey"
                            2 => "B&#46; Erdtmann"
                            3 => "M&#46; Salvador"
                            4 => "F&#46; Rombaldi"
                            5 => "A&#46; Santin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.psychres.2006.03.025"
                      "Revista" => array:7 [
                        "tituloSerie" => "Psychiatry Res"
                        "fecha" => "2007"
                        "volumen" => "153"
                        "numero" => "1"
                        "paginaInicial" => "27"
                        "paginaFinal" => "32"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17582509"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of the arginine-nitric oxide pathway in the pathogenesis of bipolar affective disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Yanik"
                            1 => "H&#46; Vural"
                            2 => "H&#46; Tutkun"
                            3 => "S&#46;S&#46; Zoroglu"
                            4 => "H&#46;A&#46; Savas"
                            5 => "H&#46; Herken"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00406-004-0453-x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Eur Arch Psychiatry Clin Neurosci"
                        "fecha" => "2004"
                        "volumen" => "254"
                        "numero" => "1"
                        "paginaInicial" => "43"
                        "paginaFinal" => "47"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14991378"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode&#58; a possible role for lithium antioxidant effects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Machado-Vieira"
                            1 => "A&#46;C&#46; Andreazza"
                            2 => "C&#46;I&#46; Viale"
                            3 => "V&#46; Zanatto"
                            4 => "V&#46; Cereser Jr&#46;"
                            5 => "R&#46; da Silva Vargas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neulet.2007.05.016"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurosci Lett"
                        "fecha" => "2007"
                        "volumen" => "421"
                        "numero" => "1"
                        "paginaInicial" => "33"
                        "paginaFinal" => "36"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17548157"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Activities of superoxide dismutase and glutathione peroxidase in schizophrenic and manic-depressive patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46;S&#46; Abdalla"
                            1 => "H&#46;P&#46; Monteiro"
                            2 => "J&#46;A&#46; Oliveira"
                            3 => "E&#46;J&#46; Bechara"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Chem"
                        "fecha" => "1986"
                        "volumen" => "32"
                        "numero" => "5"
                        "paginaInicial" => "805"
                        "paginaFinal" => "807"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2870827"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reduced antioxidant defense systems in schizophrenia and bipolar I disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Raffa"
                            1 => "S&#46; Barhoumi"
                            2 => "F&#46; Atig"
                            3 => "C&#46; Fendri"
                            4 => "A&#46; Kerkeni"
                            5 => "A&#46; Mechri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pnpbp.2012.07.013"
                      "Revista" => array:7 [
                        "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry"
                        "fecha" => "2012"
                        "volumen" => "39"
                        "numero" => "2"
                        "paginaInicial" => "371"
                        "paginaFinal" => "375"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22841966"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment with lithium&#44; alone or in combination with olanzapine&#44; relieves oxidative stress but increases atherogenic lipids in bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Aliyazicioglu"
                            1 => "B&#46; Kural"
                            2 => "M&#46; Colak"
                            3 => "S&#46;C&#46; Karahan"
                            4 => "S&#46; Ayvaz"
                            5 => "O&#46; Deger"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1620/tjem.213.79"
                      "Revista" => array:7 [
                        "tituloSerie" => "Tohoku J Exp Med"
                        "fecha" => "2007"
                        "volumen" => "213"
                        "numero" => "1"
                        "paginaInicial" => "79"
                        "paginaFinal" => "87"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17785956"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of lithium on oxidative stress parameters in healthy subjects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Khairova"
                            1 => "r&#46;R&#46; Pawa"
                            2 => "G&#46; Salvadore"
                            3 => "M&#46;F&#46; Juruena"
                            4 => "R&#46;T&#46; de Sousa"
                            5 => "M&#46;G&#46; Soeiro-de-Souza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3892/mmr.2011.732"
                      "Revista" => array:7 [
                        "tituloSerie" => "Mol Med Rep"
                        "fecha" => "2012"
                        "volumen" => "5"
                        "numero" => "3"
                        "paginaInicial" => "680"
                        "paginaFinal" => "682"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22200861"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Selek"
                            1 => "H&#46;A&#46; Savas"
                            2 => "H&#46;S&#46; Gergerlioglu"
                            3 => "F&#46; Bulbul"
                            4 => "E&#46; Uz"
                            5 => "M&#46; Yumru"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jad.2007.08.006"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Affect Disord"
                        "fecha" => "2008"
                        "volumen" => "107"
                        "numero" => "1&#8211;3"
                        "paginaInicial" => "89"
                        "paginaFinal" => "94"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17869345"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "N-acetyl cysteine for depressive symptoms in bipolar disorder &#8211; a double-blind randomized placebo-controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Berk"
                            1 => "D&#46;L&#46; Copolov"
                            2 => "O&#46; Dean"
                            3 => "K&#46; Lu"
                            4 => "S&#46; Jeavons"
                            5 => "I&#46; Schapkaitz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.biopsych.2008.04.022"
                      "Revista" => array:7 [
                        "tituloSerie" => "Biol Psychiatry"
                        "fecha" => "2008"
                        "volumen" => "64"
                        "numero" => "6"
                        "paginaInicial" => "468"
                        "paginaFinal" => "475"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18534556"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression&#58; an open label trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Berk"
                            1 => "O&#46; Dean"
                            2 => "S&#46;M&#46; Cotton"
                            3 => "C&#46;S&#46; Gama"
                            4 => "F&#46; Kapczinski"
                            5 => "B&#46;S&#46; Fernandes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jad.2011.06.005"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Affect Disord"
                        "fecha" => "2011"
                        "volumen" => "135"
                        "numero" => "1&#8211;3"
                        "paginaInicial" => "389"
                        "paginaFinal" => "394"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21719110"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia&#63; Animal models and relevance to clinical practice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "O&#46;M&#46; Dean"
                            1 => "M&#46; van den Buuse"
                            2 => "A&#46;I&#46; Bush"
                            3 => "D&#46;L&#46; Copolov"
                            4 => "F&#46; Ng"
                            5 => "S&#46; Dodd"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2174/092986709788803060"
                      "Revista" => array:7 [
                        "tituloSerie" => "Curr Med Chem"
                        "fecha" => "2009"
                        "volumen" => "16"
                        "numero" => "23"
                        "paginaInicial" => "2965"
                        "paginaFinal" => "2976"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19689277"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of antioxidant N-acetyl-L-cysteine on behavioral changes and neurotoxicity in rats after administration of methamphetamine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46; Fukami"
                            1 => "K&#46; Hashimoto"
                            2 => "K&#46; Koike"
                            3 => "N&#46; Okamura"
                            4 => "E&#46; Shimizu"
                            5 => "M&#46; Iyo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.brainres.2004.04.072"
                      "Revista" => array:7 [
                        "tituloSerie" => "Brain Res"
                        "fecha" => "2004"
                        "volumen" => "1016"
                        "numero" => "1"
                        "paginaInicial" => "90"
                        "paginaFinal" => "95"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15234256"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "N-acetyl cysteine add-on treatment for bipolar II disorder&#58; a subgroup analysis of a randomized placebo-controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;V&#46; Magalhaes"
                            1 => "O&#46;M&#46; Dean"
                            2 => "A&#46;I&#46; Bush"
                            3 => "D&#46;L&#46; Copolov"
                            4 => "G&#46;S&#46; Malhi"
                            5 => "K&#46; Kohlmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jad.2010.08.001"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Affect Disord"
                        "fecha" => "2011"
                        "volumen" => "129"
                        "numero" => "1&#8211;3"
                        "paginaInicial" => "317"
                        "paginaFinal" => "320"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20800897"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mood stabilizing drugs lamotrigine and olanzapine increase expression and activity of glutathione S-transferase in primary cultured rat cerebral cortical cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Bakare"
                            1 => "L&#46; Shao"
                            2 => "J&#46; Cui"
                            3 => "L&#46;T&#46; Young"
                            4 => "J&#46;F&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neulet.2009.03.022"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurosci Lett"
                        "fecha" => "2009"
                        "volumen" => "455"
                        "numero" => "1"
                        "paginaInicial" => "70"
                        "paginaFinal" => "73"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19429109"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Haloperidol and clozapine&#44; but not olanzapine&#44; induces oxidative stress in rat brain"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Reinke"
                            1 => "M&#46;R&#46; Martins"
                            2 => "M&#46;S&#46; Lima"
                            3 => "J&#46;C&#46; Moreira"
                            4 => "F&#46; Dal-Pizzol"
                            5 => "J&#46; Quevedo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neulet.2004.09.032"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurosci Lett"
                        "fecha" => "2004"
                        "volumen" => "372"
                        "numero" => "1-2"
                        "paginaInicial" => "157"
                        "paginaFinal" => "160"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15531108"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comparative study of oxidative stress and interrelationship of important antioxidants in haloperidol and olanzapine treated patients suffering from schizophrenia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "O&#46;P&#46; Singh"
                            1 => "I&#46; Chakraborty"
                            2 => "A&#46; Dasgupta"
                            3 => "S&#46; Datta"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4103/0019-5545.43627"
                      "Revista" => array:7 [
                        "tituloSerie" => "Indian J Psychiatry"
                        "fecha" => "2008"
                        "volumen" => "50"
                        "numero" => "3"
                        "paginaInicial" => "171"
                        "paginaFinal" => "176"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19742187"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Olanzapine and quetiapine protect PC12 cells from beta-amyloid peptide&#40;25-35&#41;-induced oxidative stress and the ensuing apoptosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "H&#46; Wang"
                            1 => "H&#46; Xu"
                            2 => "L&#46;E&#46; Dyck"
                            3 => "X&#46;M&#46; Li"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jnr.20570"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Neurosci Res"
                        "fecha" => "2005"
                        "volumen" => "81"
                        "numero" => "4"
                        "paginaInicial" => "572"
                        "paginaFinal" => "580"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15948179"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of risperidone and haloperidol on superoxide dismutase and nitric oxide in schizophrenia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "X&#46;Y&#46; Zhang"
                            1 => "D&#46;F&#46; Zhou"
                            2 => "Y&#46;C&#46; Shen"
                            3 => "P&#46;Y&#46; Zhang"
                            4 => "W&#46;F&#46; Zhang"
                            5 => "J&#46; Liang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neuropharm.2011.12.014"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neuropharmacology"
                        "fecha" => "2012"
                        "volumen" => "62"
                        "numero" => "5&#8211;6"
                        "paginaInicial" => "1928"
                        "paginaFinal" => "1934"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22227558"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "F&#46; Kapczinski"
                            1 => "B&#46;N&#46; Frey"
                            2 => "A&#46;C&#46; Andreazza"
                            3 => "M&#46; Kauer-Sant&#8217;Anna"
                            4 => "A&#46;B&#46; Cunha"
                            5 => "R&#46;M&#46; Post"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Braz J Psychiatr"
                        "fecha" => "2008"
                        "volumen" => "30"
                        "numero" => "3"
                        "paginaInicial" => "243"
                        "paginaFinal" => "245"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The empirical redefinition of the psychometric criteria for remission in bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Berk"
                            1 => "F&#46; Ng"
                            2 => "W&#46;V&#46; Wang"
                            3 => "J&#46;R&#46; Calabrese"
                            4 => "P&#46;B&#46; Mitchell"
                            5 => "G&#46;S&#46; Malhi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jad.2007.06.011"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Affect Disord"
                        "fecha" => "2008"
                        "volumen" => "106"
                        "numero" => "1-2"
                        "paginaInicial" => "153"
                        "paginaFinal" => "158"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17655936"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Analysis of relative gene expression data using real-time quantitative PCR and the 2&#40;-Delta Delta C&#40;T&#41;&#41; Method"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46;J&#46; Livak"
                            1 => "T&#46;D&#46; Schmittgen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1006/meth.2001.1262"
                      "Revista" => array:7 [
                        "tituloSerie" => "Methods"
                        "fecha" => "2001"
                        "volumen" => "25"
                        "numero" => "4"
                        "paginaInicial" => "402"
                        "paginaFinal" => "408"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11846609"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "I&#46;S&#46; Young"
                            1 => "E&#46;R&#46; Trimble"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/000456329102800514"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Clin Biochem"
                        "fecha" => "1991"
                        "volumen" => "28"
                        "numero" => "Pt 5"
                        "paginaInicial" => "504"
                        "paginaFinal" => "508"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1958055"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changes in nitric oxide level and superoxide dismutase activity during antimanic treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46;S&#46; Gergerlioglu"
                            1 => "H&#46;A&#46; Savas"
                            2 => "F&#46; Bulbul"
                            3 => "S&#46; Selek"
                            4 => "UE"
                            5 => "M&#46; Yumru"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pnpbp.2006.12.020"
                      "Revista" => array:7 [
                        "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry"
                        "fecha" => "2007"
                        "volumen" => "31"
                        "numero" => "3"
                        "paginaInicial" => "697"
                        "paginaFinal" => "702"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17303295"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative stress in early stage Bipolar Disorder and the association with response to lithium"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;T&#46; de Sousa"
                            1 => "C&#46;A&#46; Zarate Jr&#46;"
                            2 => "M&#46;V&#46; Zanetti"
                            3 => "A&#46;C&#46; Costa"
                            4 => "L&#46;L&#46; Talib"
                            5 => "W&#46;F&#46; Gattaz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jpsychires.2013.11.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Psychiatr Res"
                        "fecha" => "2014"
                        "volumen" => "50"
                        "paginaInicial" => "36"
                        "paginaFinal" => "41"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24332923"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Specific subcellular changes in oxidative stress in prefrontal cortex from patients with bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;C&#46; Andreazza"
                            1 => "J&#46;F&#46; Wang"
                            2 => "F&#46; Salmasi"
                            3 => "L&#46; Shao"
                            4 => "L&#46;T&#46; Young"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jnc.12316"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Neurochem"
                        "fecha" => "2013"
                        "volumen" => "127"
                        "numero" => "4"
                        "paginaInicial" => "552"
                        "paginaFinal" => "561"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23692477"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Decreased mRNA expression of uncoupling protein 2&#44; a mitochondrial proton transporter&#44; in post-mortem prefrontal cortex from patients with bipolar disorder and schizophrenia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46;D&#46; Gigante"
                            1 => "A&#46;C&#46; Andreazza"
                            2 => "B&#46; Lafer"
                            3 => "L&#46;N&#46; Yatham"
                            4 => "C&#46;L&#46; Beasley"
                            5 => "L&#46;T&#46; Young"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neulet.2011.09.064"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurosci Lett"
                        "fecha" => "2011"
                        "volumen" => "505"
                        "numero" => "1"
                        "paginaInicial" => "47"
                        "paginaFinal" => "51"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22001364"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Decreased levels of glutathione&#44; the major brain antioxidant&#44; in post-mortem prefrontal cortex from patients with psychiatric disorders"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;W&#46; Gawryluk"
                            1 => "J&#46;F&#46; Wang"
                            2 => "A&#46;C&#46; Andreazza"
                            3 => "L&#46; Shao"
                            4 => "L&#46;T&#46; Young"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1017/S1461145710000805"
                      "Revista" => array:7 [
                        "tituloSerie" => "Int J Neuropsychopharmacol"
                        "fecha" => "2011"
                        "volumen" => "14"
                        "numero" => "1"
                        "paginaInicial" => "123"
                        "paginaFinal" => "130"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20633320"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;C&#46; Andreazza"
                            1 => "F&#46; Kapczinski"
                            2 => "M&#46; Kauer-Sant&#8217;Anna"
                            3 => "J&#46;C&#46; Walz"
                            4 => "D&#46;J&#46; Bond"
                            5 => "C&#46;A&#46; Goncalves"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Psychiatry Neurosci"
                        "fecha" => "2009"
                        "volumen" => "34"
                        "numero" => "4"
                        "paginaInicial" => "263"
                        "paginaFinal" => "271"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19568477"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Thiobarbituric acid reactive substances &#40;TBARS&#41; is a state biomarker of oxidative stress in bipolar patients in a manic phase"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;C&#46; Tsai"
                            1 => "T&#46;L&#46; Huang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jad.2014.10.045"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Affect Disord"
                        "fecha" => "2015"
                        "volumen" => "173"
                        "paginaInicial" => "22"
                        "paginaFinal" => "26"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25462391"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Olanzapine protects PC12 cells from oxidative stress induced by hydrogen peroxide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Z&#46; Wei"
                            1 => "O&#46; Bai"
                            2 => "J&#46;S&#46; Richardson"
                            3 => "D&#46;D&#46; Mousseau"
                            4 => "X&#46;M&#46; Li"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jnr.10668"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Neurosci Res"
                        "fecha" => "2003"
                        "volumen" => "73"
                        "numero" => "3"
                        "paginaInicial" => "364"
                        "paginaFinal" => "368"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12868070"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder&#44; schizophrenia&#44; and healthy subjects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Gubert"
                            1 => "L&#46; Stertz"
                            2 => "B&#46; Pfaffenseller"
                            3 => "B&#46;S&#46; Panizzutti"
                            4 => "G&#46;T&#46; Rezin"
                            5 => "R&#46; Massuda"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jpsychires.2013.06.018"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Psychiatr Res"
                        "fecha" => "2013"
                        "volumen" => "47"
                        "numero" => "10"
                        "paginaInicial" => "1396"
                        "paginaFinal" => "1402"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23870796"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peripheral oxidative damage in early-stage mood disorders&#58; a nested population-based case-control study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;V&#46; Magalhaes"
                            1 => "K&#46; Jansen"
                            2 => "R&#46;T&#46; Pinheiro"
                            3 => "G&#46;D&#46; Colpo"
                            4 => "L&#46;L&#46; da Motta"
                            5 => "F&#46; Klamt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1017/S1461145711001532"
                      "Revista" => array:7 [
                        "tituloSerie" => "Int J Neuropsychopharmacol"
                        "fecha" => "2012"
                        "volumen" => "15"
                        "numero" => "8"
                        "paginaInicial" => "1043"
                        "paginaFinal" => "1050"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22008234"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of mood stabilizers on DNA damage in an animal model of mania"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;C&#46; Andreazza"
                            1 => "M&#46; Kauer-Sant&#8217;Anna"
                            2 => "B&#46;N&#46; Frey"
                            3 => "L&#46; Stertz"
                            4 => "C&#46; Zanotto"
                            5 => "L&#46; Ribeiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Psychiatry Neurosci"
                        "fecha" => "2008"
                        "volumen" => "33"
                        "numero" => "6"
                        "paginaInicial" => "516"
                        "paginaFinal" => "524"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18982174"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;N&#46; Frey"
                            1 => "S&#46;S&#46; Valvassori"
                            2 => "G&#46;Z&#46; Reus"
                            3 => "M&#46;R&#46; Martins"
                            4 => "F&#46;C&#46; Petronilho"
                            5 => "K&#46; Bardini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Psychiatry Neurosci"
                        "fecha" => "2006"
                        "volumen" => "31"
                        "numero" => "5"
                        "paginaInicial" => "326"
                        "paginaFinal" => "332"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16951735"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mood stabilizer lithium inhibits amphetamine-increased 4-hydroxynonenal-protein adducts in rat frontal cortex"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46; Tan"
                            1 => "L&#46;T&#46; Young"
                            2 => "L&#46; Shao"
                            3 => "Y&#46; Che"
                            4 => "W&#46;G&#46; Honer"
                            5 => "J&#46;F&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1017/S1461145711001416"
                      "Revista" => array:8 [
                        "tituloSerie" => "Int J Neuropsychopharmacol"
                        "fecha" => "2012"
                        "volumen" => "15"
                        "numero" => "9"
                        "paginaInicial" => "1275"
                        "paginaFinal" => "1285"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21939588"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0211139X14002509"
                          "estado" => "S300"
                          "issn" => "0211139X"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of lithium therapy on Na&#43;-K&#43;-ATPase activity and lipid peroxidation in bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "U&#46; Banerjee"
                            1 => "A&#46; Dasgupta"
                            2 => "J&#46;K&#46; Rout"
                            3 => "O&#46;P&#46; Singh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pnpbp.2011.12.006"
                      "Revista" => array:7 [
                        "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry"
                        "fecha" => "2012"
                        "volumen" => "37"
                        "numero" => "1"
                        "paginaInicial" => "56"
                        "paginaFinal" => "61"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22230647"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased oxidative stress and DNA damage in bipolar disorder&#58; a twin-case report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;N&#46; Frey"
                            1 => "A&#46;C&#46; Andreazza"
                            2 => "M&#46; Kunz"
                            3 => "F&#46;A&#46; Gomes"
                            4 => "J&#46; Quevedo"
                            5 => "M&#46; Salvador"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pnpbp.2006.06.011"
                      "Revista" => array:7 [
                        "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry"
                        "fecha" => "2007"
                        "volumen" => "31"
                        "numero" => "1"
                        "paginaInicial" => "283"
                        "paginaFinal" => "285"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16859818"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A combined analysis of worldwide studies demonstrates an association between bipolar disorder and tobacco smoking behaviors in adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;G&#46; Jackson"
                            1 => "F&#46;J&#46; Diaz"
                            2 => "L&#46; Lopez"
                            3 => "J&#46; de Leon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/bdi.12319"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bipolar Disord"
                        "fecha" => "2015"
                        "volumen" => "17"
                        "paginaInicial" => "575"
                        "paginaFinal" => "597"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26238269"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mitochondria as a possible target for nicotine action"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Dominika"
                            1 => "R&#46;W&#46; Mariusz"
                            2 => "M&#46; Bernadeta"
                            3 => "D&#46; Karolina"
                            4 => "P&#46; Monika"
                            5 => "P&#46;K&#46; Paulina"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10863-019-09800-z"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Bioenerg Biomembr"
                        "fecha" => "2019"
                        "volumen" => "51"
                        "numero" => "4"
                        "paginaInicial" => "259"
                        "paginaFinal" => "276"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31197632"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/02136163/0000003400000004/v1_202010090651/S0213616320300690/v1_202010090651/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "64426"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/02136163/0000003400000004/v1_202010090651/S0213616320300690/v1_202010090651/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213616320300690?idApp=UINPBA00004N"
]

Article information

ISSN: 02136163
Original language: English

DOI:10.1016/j.ejpsy.2020.08.001

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	6	1	7
2024 October	31	3	34
2024 September	28	23	51
2024 August	28	11	39
2024 July	49	2	51
2024 June	37	1	38
2024 May	32	8	40
2024 April	42	6	48
2024 March	38	10	48
2024 February	31	4	35
2024 January	28	9	37
2023 December	27	2	29
2023 November	30	13	43
2023 October	36	3	39
2023 September	29	0	29
2023 August	23	2	25
2023 July	23	5	28
2023 June	27	12	39
2023 May	59	13	72
2023 April	76	6	82
2023 March	45	5	50
2023 February	40	5	45
2023 January	74	2	76
2022 December	35	9	44
2022 November	40	12	52
2022 October	16	6	22
2022 September	26	10	36
2022 August	30	8	38
2022 July	13	5	18
2022 June	14	6	20
2022 May	25	6	31
2022 April	16	6	22
2022 March	28	10	38
2022 February	26	6	32
2022 January	58	7	65
2021 December	32	14	46
2021 November	30	8	38
2021 October	19	9	28
2020 October	6	0	6

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter