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"documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Psiquiatr Biol . 2022;29:" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Revisión</span>" "titulo" => "Creating the optimal diet: Diet can reduce the symptoms of schizophrenia" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Crear la dieta óptima: la dieta puede reducir los síntomas de la esquizofrenia" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Kalyani Rajalingham" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Kalyani" "apellidos" => "Rajalingham" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1134593422000148?idApp=UINPBA00004N" "url" => "/11345934/0000002900000002/v1_202211190651/S1134593422000148/v1_202211190651/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Revisión</span>" "titulo" => "Investigation of the functional vesicular monoamine transporter 1 (VMAT1/SLC18A1) Thr136Ile gene variant in bipolar disorder" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Zeynep Yegin, Gokhan Sarisoy, Ayse Erguner Aral, Haydar Koc" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Zeynep" "apellidos" => "Yegin" "email" => array:1 [ 0 => "zyegin@sinop.edu.tr" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cr0005" ] ] ] 1 => array:3 [ "nombre" => "Gokhan" "apellidos" => "Sarisoy" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "af0010" ] ] ] 2 => array:3 [ "nombre" => "Ayse" "apellidos" => "Erguner Aral" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "af0010" ] ] ] 3 => array:3 [ "nombre" => "Haydar" "apellidos" => "Koc" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "af0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Medical Laboratory Techniques Program, Vocational School of Health Services, Sinop University, Sinop, Turkey" "etiqueta" => "a" "identificador" => "af0005" ] 1 => array:3 [ "entidad" => "Department of Psychiatry, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey" "etiqueta" => "b" "identificador" => "af0010" ] 2 => array:3 [ "entidad" => "Department of Statistics, Faculty of Science, Cankiri Karatekin University, Cankiri, Turkey" "etiqueta" => "c" "identificador" => "af0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudio de la variante Thr136Ile del gen transportador 1 vesicular de monoaminas (VMAT1/SLC18A1) en el trastorno bipolar" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Bipolar disorder (BD) is an episodic recurrent mood disturbance ranging from mania to severe depression. Several clinical subtypes are defined including bipolar disorder type I, bipolar disorder type II, and bipolar type schizoaffective disorder.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> The heritable nature of BD was proven to some extent in studies which used first-degree relatives and twins of affected individuals. Especially earlier-onset bipolar disorder seemed to be associated with increased familial risk.<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a> Since the familial/genetic determinants of psychiatric disorders are not entirely distinct and they can even be quite heterogeneous, the discovery of susceptibility loci and candidate genes may have significant contributions to unravel the molecular risk drivers of psychopathologies.</p><p id="p0010" class="elsevierStylePara elsevierViewall">Vesicular monoamine transporters (VMATs) are presynaptic membrane transport proteins which play quite significant roles in the packaging of monoaminergic neurotransmitters (serotonin, dopamine, adrenaline, noradrenaline, histamine) into presynaptic storage vesicles.<a class="elsevierStyleCrossRefs" href="#bb0015"><span class="elsevierStyleSup">3–5</span></a> Two VMATs encoded by separate genes, VMAT1 (SLC18A1) and VMAT2 (SLC18A2), are located on chromosome 8p21 and chromosome 10q25, respectively. They are structurally related but pharmacologically distinct entities since they differ in substrate affinity. While VMAT1 displays higher affinity for serotonin, VMAT2 can transport histamine.<a class="elsevierStyleCrossRefs" href="#bb0030"><span class="elsevierStyleSup">6–8</span></a> Since the dysregulation of noradrenergic, dopaminergic, serotonergic, and cholinergic systems as well as the hypothalamic–pituitary axis has been identified in patients with BD,<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a> VMAT1 is an attractive candidate gene to study the underlying molecular mechanisms of BD pathogenesis. The elevated in vitro expression levels of VMAT1 with lithium and valproate<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a> might be useful for therapeutic drug intervention studies. VMAT1 mRNA expression is important in glial differentiation and cerebellar granule cell migration and/or differentiation.<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a> To investigate the role of VMAT1 expression in the brain and its potential role in neuropsychiatric disorders, Multani et al. (2013) compared wild-type and VMAT1 knock-out (KO) mice using qPCR and immunohistochemistry and demonstrated the expression of VMAT1 in the brain. Mice lacking VMAT1 had neurocognitive deficits since VMAT1 deletion resulted in increased hippocampal apoptosis and decreased neurogenesis.<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">Variants of VMAT1 gene may play a role in psychiatric disorder etiology since they alter transporter expression. We thus aimed to investigate whether functional VMAT1 Thr136Ile (rs1390938) gene variant could cause susceptibility to bipolar disorder in a Turkish population.</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Materials and methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Subjects</span><p id="p0020" class="elsevierStylePara elsevierViewall">One hundred twenty unrelated BD patients participated in this study. Patients were collected at a single-center (Ondokuz Mayis University, Faculty of Medicine, Department of Psychiatry) and had a BD diagnosis as defined by DSM-V criteria. The control group subjects were chosen from volunteers of university staff (One hundred one healthy individuals) with no previous history of psychiatric or neurological disease. Both the cases and controls were of Turkish descent. All samples were collected in accordance with the Declaration of Helsinki and the study was approved by the Medical Ethics Committee of Ondokuz Mayis University (OMU KAEK 2020/104).</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">DNA analysis</span><p id="p0025" class="elsevierStylePara elsevierViewall">Blood samples were collected from all human subjects in EDTA containing tubes. DNA isolation was performed using a QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Germany). Genotyping of VMAT1 Thr136Ile (rs1390938) was made using PCR-RFLP method.<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> PCR reaction was carried out in gradient thermal cycler system using 1x Taq buffer, 2 mM MgCl<span class="elsevierStyleInf">2</span>, 0.2 mM dNTP, 0.5 μM of forward and reverse primer pair, 1.5 U Taq DNA polymerase (Thermo Fisher Scientific, MA, USA) and ~ 150–200 ng of DNA sample. Thermal cycler conditions were as follows: A pre-denaturation step for 6 min at 94 °C followed by 35 cycles including 40 s denaturation at 94 °C, 45 s annealing at 56 °C, and 45 s extension at 72 °C. Final extension step was performed for 12 min at 72 °C. VMAT1 Thr136Ile (rs1390938) genotypes were determined with RFLP. The digestion of the amplicons using BsmA1 restriction enzyme (New England Biolabs, Ipswich, MA, USA) for an hour at 55 °C resulted in AA (Ile): 468 bp, GG (Thr): 129 bp and 339 bp amplicons while heterozygotes produced both.</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Statistical analysis</span><p id="p0030" class="elsevierStylePara elsevierViewall">Statistical analyses were carried out by using the SPSS statistics software version 22. Hardy–Weinberg equilibrium was analyzed using the χ2 test. Descriptive statistics for the categorical and numerical variables of the patient and control groups were given as n (%) and mean ± sd, respectively. The distribution of genotype and allele frequencies between the patient and control groups and their relationship with bipolar disorder risk were evaluated using the odds ratios and 95% confidence intervals. The relationship between some clinical variables and genotypes was examined by Kruskal-Wallis H test or ANOVA (F test). In addition, the relationship between categorical variables and genotypes was examined using Fisher's exact test. All the results were considered significant at the P < 0.05 level.</p></span></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Results</span><p id="p0035" class="elsevierStylePara elsevierViewall">A total of 221 individuals (120 patients and 101 healthy control individuals) participated in the study. While the mean age of the patients in the study was 39.11 ± 12.62, the mean age of the individuals in the control group was 39.57 ± 9.47. Gender ratios for the study group were as follows: 59.2% of the patients were female and 40.8% were male and 37.6% of the participants in the control group were female and 62.4% were male. The mean of the age of disease onset was 23.59 ± 7.62 years and mean disease duration was 15.28 ± 11.33 years. First episodes were manic in 85 (70.8%) and depressive in 35 (29.2%) individuals. While hypomania was present in 20 (16.7%) patients, the rest of the patients (100 patients (83.3%)) were not characterized with hypomania. Total episode number was 8.29 ± 6.81 (Depressive episode number: 3.26 ± 3.42; manic episode number: 4.68 ± 3.91; hypomanic episode number: 0.33 ± 0.91).</p><p id="p0040" class="elsevierStylePara elsevierViewall">The distribution of genotype and allele frequencies for VMAT1 Thr136Ile (rs1390938) between the patients and control group and their relationship with bipolar disorder risk were evaluated and no statistically significant relationship was observed (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>). None of the genotypes deviated significantly from those expected from Hardy–Weinberg equilibrium neither for cases nor for controls.</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0045" class="elsevierStylePara elsevierViewall">Some clinical parameters were also considered to determine whether VMAT1 Thr136Ile genotypes would affect disease sub-parameters. The relationship between categorical characteristics (gender, first episode, hypomania presence) and genotypes was examined with Fisher's exact test. No significant statistical relationship was found according to the results (Gender: Fisher = 0.664, p = 0.742; First episode: Fisher = 1.302, p = 0.557; Hypomania presence: Fisher = 1.521, p = 0.554). The difference between the mean number of hypomanic episodes and the genotypes was tested with ANOVA (F test) and no statistical difference was found (F = 1.623, p = 0.202). The other intriguing variables of interest (the age of disease onset, disease duration, total episode number, depressive episode number, manic episode number) were evaluated with Kruskal-Wallis H test since the variables of interest were not normally distributed. It was determined that there was no difference between VMAT1 genotypes and the related variables (<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>).</p><elsevierMultimedia ident="t0010"></elsevierMultimedia></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Discussion</span><p id="p0050" class="elsevierStylePara elsevierViewall">From an evolutionary perspective, the emergence of psychiatric disorders (PDs) would be linked to the evolution of the human brain and PDs might have been developed as maladaptive by-products of adaptive human evolution.<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> SLC18A1 (VMAT1: Vesicular monoamine transporter 1) is a positively selected gene in the human lineage and has a human-unique variant (Thr136Ile) differently from other mammals (Excluding <span class="elsevierStyleItalic">Homo sapiens</span>, other 14 mammals analyzed carried Asn at the 136th site of VMAT1, while the archaic and modern humans carried only 136Thr or both 136Thr and 136Ile, respectively). Emergence time of 136Ile (~<span class="elsevierStyleHsp" style=""></span>100.000 years ago) shown with coalescent simulations was coherent with the Out-of-Africa migration model. Thus, it can be hypothesized that 136Thr evolved in the archaic human lineage from great apes by positive natural selection and the increase of 136Ile frequency occurred after the migration of modern humans into Europe and maintained in non-African populations. The evolution of Asn to Thr at the 136th site of VMAT1 might have resulted in more anxiety-related phenotypes.<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a></p><p id="p0055" class="elsevierStylePara elsevierViewall">We evaluated the genotype and allele frequencies for VMAT1 Thr136Ile (rs1390938) between the patients with BD and control group in terms of susceptibility to bipolar disorder but no association was present. The minor A allele frequency was 0.279 in BD patients and 0.282 in control group individuals. There was also not any difference in terms of genotypes (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>). The possible effects of VMAT1 Thr136Ile (rs1390938) variants on gender, first episode, and hypomania presence were investigated but there was no association. Moreover, we also analyzed some other clinically significant parameters such as the age of disease onset, disease duration, total episode number, depressive episode number and manic episode number but no association was present between VMAT1 genotypes and the investigated features (<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>).</p><p id="p0060" class="elsevierStylePara elsevierViewall">Previous studies evaluated VMAT1 Thr136Ile variant and presented significant findings. VMAT1 Thr136Ile (rs1390938) is functional in vitro and ‘hyperfunction’ Ile allele results in increased monoamine transport into presynaptic vesicles. The association of ‘hyperfunction’ allele with threat-related amygdala reactivity was assessed. Increased amygdala reactivity and decreased habituation were found. The significance and consistency of this information was discussed in the light of some phenotypes in some diseases, such as increased reactivity in bipolar disorder during mania and decreased habituation in posttraumatic stress disorder (PTSD).<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> In our study, we did not find any association between VMAT1 Thr136Ile (rs1390938) genotypes and median manic/depressive episode numbers, which must be definitely further evaluated in other studies. The first study investigating VMAT1 Thr136Ile variant in bipolar disorder revealed the association of this potential functional polymorphism with BD.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> To the best of our knowledge, there was no study aiming to elucidate the potential effect of this variant in BD thereafter. Hence, our study is the second investigation in a different population. Further designs such as increasing the cohort number in a multi-centered model are needed for the future.</p><p id="p0065" class="elsevierStylePara elsevierViewall">VMAT1 Thr136Ile variant was investigated in schizophrenia in a Japanese population but there was no significant difference in genotype or allele distributions between patients and controls. However, a susceptibility effect was reported for a different variant (VMAT1 Thr98Ser) only in females.<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> Lohoff et al. (2008) reported the genetic phenomenon of ‘heterosis’ by implying that women heterozygous for VMAT1 Thr/Ile displayed significantly higher State–Trait Anxiety Inventory (STAI) scores when compared with either Ile/Ile or Thr/Thr homozygotes.<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a> The minor allele of the VMAT1 missense variant Thr136Ile was associated with reduced connectivity in neural networks that show a general increased connectivity in alcoholics, emphasizing the potential protective effect.<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> The protective effect of the minor allele was also emphasized in Estonian Children Personality Behavior and Health Study<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> consisting of two cohorts (Cohort 1: Initially 9 and recalled at ages 15 and 18 years; Cohort 2: Initially 15 and recalled at ages 18 and 25 years) in which self-reports on impulsivity, anxiety, depressiveness, neuroticism, alcohol use and psychiatric assessment based on DSM-IV at age 25 years were evaluated. Subjects homozygous for the hyperfunction allele (AA; Ile/Ile) displayed significantly lower likelihood of having being diagnosed with an affective, anxiety, and/or alcohol use disorder at some point of their life compared with G allele carriers. These findings reflecting the potential protective effect of A allele are also coherent with the BD report mentioned above. The gain of functional A allele (136Ile) seems to be protective against bipolar disorder.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> The minor allele (A) of the missense variant VMAT1 Thr136Ile was found to be associated with decreased alcohol withdrawal severity based on measurements by Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar), possibly via the mechanism of increased monoamine neurotransmitter transport into vesicles.<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> The investigation of VMAT1 non-synonymous SNPs in Iranian patients with autism indicated significant over-presentation of G allele in autism cases when compared with controls, reflecting the potential protective effect of A allele against the disease. AA genotype of VMAT1 Thr136Ile (rs1390938) was protective against autism spectrum disorders (ASD) under dominant and recessive genetic models.<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> In a study investigating the possible association between three VMAT1 SNPs including rs1390938 and suicide behavior, no difference was observed in neither genotype nor allele frequencies.<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> In spite of the possible significance of VMATs in the development of neuropsychiatric disease models, it is undoubtedly clear that very limited studies focused on VMAT1 Thr136Ile (rs1390938) up to now in the literature.</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Conclusion</span><p id="p0070" class="elsevierStylePara elsevierViewall">In conclusion, our study did not find any association between VMAT1 Thr136Ile (rs1390938) gene variant and bipolar disorder risk in Turkish population. The analyses of some clinical subparameters in BD patients in order to gain a possible predictive perspective for the patient risk analysis did not reflect a statistically significant association. To the best of our knowledge, this is the second analysis of human-unique VMAT1 Thr136Ile (rs1390938) variant in bipolar disorder and also the first one in Turkish population. However, our study has some limitations to consider; the first one is the relatively small number of population cohort stemming from conducting the research at a single-center. Therefore, further large-scale research both in our population and other populations are strongly recommended by the researchers. Our other limitation was to focus on a single variant. Further studies are needed to analyze more VMAT1 variants in bipolar disorder together with VMAT1 Thr136Ile (rs1390938). Obviously, studies based on the role of VMAT1 in bipolar disorder development and progression would make considerable contributions to quite limited literature data.</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Ethics approval and consent to participate</span><p id="p0075" class="elsevierStylePara elsevierViewall">The study protocol was approved by the Medical Ethics Committee of Ondokuz Mayis University (OMU KAEK 2020/104). The study was conducted in compliance with the Helsinki Declaration and written informed consent was obtained from the participants.</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Conflict of interest</span><p id="p0080" class="elsevierStylePara elsevierViewall">The authors report no conflict of interest.</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0120">Funding</span><p id="p0085" class="elsevierStylePara elsevierViewall">No funding was obtained for this study.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres1804115" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "as0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "as0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "as0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1576871" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec1576872" "titulo" => "Abbreviations" ] 3 => array:3 [ "identificador" => "xres1804114" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0025" "titulo" => "Antecedentes y Objetivos" ] 1 => array:2 [ "identificador" => "as0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "as0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "as0040" "titulo" => "Conclusión" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1576873" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "s0010" "titulo" => "Materials and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Subjects" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "DNA analysis" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "Statistical analysis" ] ] ] 7 => array:2 [ "identificador" => "s0030" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "s0035" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "s0040" "titulo" => "Conclusion" ] 10 => array:2 [ "identificador" => "s0045" "titulo" => "Ethics approval and consent to participate" ] 11 => array:2 [ "identificador" => "s0050" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "s0055" "titulo" => "Funding" ] 13 => array:2 [ "identificador" => "xack636535" "titulo" => "Acknowledgments" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-03-10" "fechaAceptado" => "2022-05-06" "PalabrasClave" => array:2 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1576871" "palabras" => array:4 [ 0 => "Bipolar disorder" 1 => "VMAT1 gene" 2 => "rs1390938" 3 => "Molecular psychiatry" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1576872" "palabras" => array:8 [ 0 => "BD" 1 => "VMAT1" 2 => "DSM-V" 3 => "PCR-RFLP" 4 => "PDs" 5 => "PTSD" 6 => "STAI" 7 => "CIWA-Ar" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1576873" "palabras" => array:4 [ 0 => "Trastorno bipolar" 1 => "Gen VMAT1" 2 => "rs1390938" 3 => "Psiquiatría molecular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Background and objectives</span><p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Bipolar disorder (BD) is an episodic and recurrent mood disturbance ranging from mania to severe depression. Because of the heterogeneity of psychiatric disorders, enlightening the possible molecular risk drivers is crucial. Vesicular monoamine transporter 1 (VMAT1) is an important candidate gene to study the underlying molecular mechanisms in BD pathogenesis since it has a significant role in the packaging of monoaminergic neurotransmitters into presynaptic storage vesicles. The aim of this study was to ascertain whether functional and evolutionarily important variant of VMAT1 gene (Thr136Ile (rs1390938)) would affect the susceptibility of the individuals to BD in a Turkish population.</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Method</span><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">One hundred twenty BD patients and one hundred one healthy control individuals were recruited for the study. Samples were genotyped using PCR-RFLP method to detect VMAT1 gene variant (Thr136Ile (rs1390938)).</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Results</span><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Contrary to our expectations, VMAT1 Thr136Ile (rs1390938) gene variant was not associated with BD in our population. There was also no relationship between VMAT1 genotypes and some clinically significant parameters in BD patients.</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Conclusion</span><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Our data showed no association between VMAT1 Thr136Ile (rs1390938) and BD in Turkish population. We strongly recommend the analysis of this variant in other populations to draw a precise conclusion about the role of this variant in bipolar disorder. Further large-scale research for the other variants of VMAT1 is also required to clarify the strong hypothesis focused on VMAT1 variants in the development of neuropsychiatric disorders.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "as0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "as0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "as0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="as0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Antecedentes y Objetivos</span><p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">El trastorno bipolar (TB) es una alteración del ánimo episódica y recurrente, que fluctúa entre la manía y la depresión severa. Debido a la heterogeneidad de los trastornos psiquiátricos, es esencial esclarecer los posibles impulsores del riesgo molecular. El transportador 1 vesicular de monoaminas (VMAT1) es un importante gen candidato para estudiar los mecanismos moleculares subyacentes en la patogenia del TB, dado que tiene un rol significativo de embalaje de los neurotransmisores monoaminérgicos en las vesículas de almacenaje presinápticas. El objetivo de este estudio fue comprobar si la variante funcional y evolutivamente importante del gen VMAT1 (Thr136Ile (rs1390938)) afectaría a la susceptibilidad de los individuos relativa a TB en una población turca.</p></span> <span id="as0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Método</span><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Se seleccionaron para el estudio ciento veinte pacientes con TB y ciento un individuos sanos. Se genotipificaron las muestras mediante el método PCR-RFLP, para detectar la variante del gen VMAT1 (Thr136Ile (rs1390938)).</p></span> <span id="as0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Resultados</span><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">Contrariamente a nuestras expectativas, la variante del gen VMAT1 (Thr136Ile (rs1390938)) no estuvo asociada al TB en nuestra población. Tampoco se encontró relación entre los genotipos de VMAT1 y algunos parámetros clínicamente significativos de los pacientes de TB.</p></span> <span id="as0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Conclusión</span><p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">Nuestros datos no reflejaron asociación ninguna entre la variante Thr136Ile (rs1390938) de VMAT1 y el TB en la población turca. Recomendamos encarecidamente el análisis de esta variante en otras poblaciones, para obtener una conclusión precisa sobre el rol de la misma en el trastorno bipolar. También son necesarios más estudios a gran escala sobre las demás variantes de VMAT1 para esclarecer la sólida hipótesis centrada en las variantes de VAT1, en cuanto al desarrollo de trastornos neuropsiquiátricos.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0025" "titulo" => "Antecedentes y Objetivos" ] 1 => array:2 [ "identificador" => "as0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "as0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "as0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Genotype \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cases</th><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controls</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">P-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">OR (95% CI)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">VMAT1 Thr136Ile \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">% \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">% \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AA \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">9 \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">7.5 \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">8 \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">7.9 \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><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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AG \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">49 \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">40.8 \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">41 \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">40.6 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.909 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.941 (0.333–2.660)</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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GG \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">62 \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">51.7 \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">52 \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">51.5 \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">0.911 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.944 (0.340–2.620)</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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A allele frequency \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">67 \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">0.279 \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">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">0.282 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.944</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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">G allele frequency \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">173 \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">0.721 \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">145 \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">0.718 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Association analysis between VMAT1 Thr136Ile (rs1390938) and bipolar disorder risk.</p>" ] ] 1 => array:8 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "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-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"></th><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="6" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">VMAT1 Thr136Ile</th><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup colgroup " rowspan="3" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" colspan="2" style="border-bottom: 2px solid black">Test and p value</th></tr><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AA</th><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AG</th><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GG</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Median \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Min-Max \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Median \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Min-Max \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Median \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Min-Max \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total episode 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">1–17 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–30 \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">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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–40 \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">K-W = 1.865 \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">p = 0.394 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Depressive episode 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">0–8 \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">2 \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">0–12 \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">2 \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">0–20 \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">K-W = 0.912 \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">p = 0.634 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Manic episode 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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">1–9 \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">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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–20 \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">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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–20 \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">K-W = 1.842 \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">p = 0.398 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The age of disease onset \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">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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17–31 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \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">10–55 \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">22.5 \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">14–48 \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">K-W = 0.004 \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">p = 0.998 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disease duration \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">13 \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">1–20 \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">16 \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">1–60 \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">12 \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">1–44 \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">K-W = 3.315 \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">p = 0.191 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Association analysis between VMAT1 Thr136Ile (rs1390938) genotypes and some clinicopathologic characteristics of BD patients.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:23 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetics of bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "N. Craddock" 1 => "P. Sklar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(13)60855-7" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2013" "volumen" => "381" "numero" => "9878" "paginaInicial" => "1654" "paginaFinal" => "1662" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23663951" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Family, twin, and adoption studies of bipolar disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.W. Smoller" 1 => "C.T. Finn" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet C: Semin Med Genet" "fecha" => "2003" "volumen" => "123C" "numero" => "1" "paginaInicial" => "48" "paginaFinal" => "58" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bb0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.W. Lohoff" 1 => "R. Hodge" 2 => "S. Narasimhan" 3 => "A. Nall" 4 => "T.N. Ferraro" 5 => "B.J. 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Investigation of the functional vesicular monoamine transporter 1 (VMAT1/SLC18A1) Thr136Ile gene variant in bipolar disorder
Estudio de la variante Thr136Ile del gen transportador 1 vesicular de monoaminas (VMAT1/SLC18A1) en el trastorno bipolar