性别相关的表观遗传学通过 SLC6A4 基因启动子区域的甲基化对躯体化产生影响。

Epigenetics-by-sex interaction for somatization conferred by methylation at the promoter region of SLC6A4 gene.

机构信息

Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona (UB), Barcelona, Spain; Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain.

Mental Health Department, Servicio Navarro de Salud, Instituto de Investigación Sanitaria de Navarra (IdisNa), Pamplona, Spain.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:125-131. doi: 10.1016/j.pnpbp.2018.09.002. Epub 2018 Sep 8.

DOI:10.1016/j.pnpbp.2018.09.002

PMID:30201454

Abstract

BACKGROUND

Depression, anxiety and somatoform disorders are all more prevalent in women than in men. However, specific biological mechanisms contributing to such sex differences remain unknown. Serotonergic pathways are involved in mood and behavior regulation and thus have been suggested to be altered in several psychiatric disorders. The serotonin transporter (SERT), encoded by SLC6A4 gene, has received major attention due to its crucial role in serotonergic transmission.

METHODS

148 monozygotic twin subjects were assessed for (i) lifetime categorical diagnosis of anxious-depressive disorders, following SCID-I-based DSM-IV criteria, and (ii) current psychiatric symptomatology, from a dimensional approach, by means of the Brief Symptom Inventory (BSI). SLC6A4 gene methylation was analyzed by means of Infinium HumanMethylation450 in a subset of the sample. CpG-specific methylation at the promoter region of SLC6A4 gene was further analyzed by means of pyrosequencing technology in the total sample.

RESULTS

SLC6A4 methylation was found to be significantly higher in women when compared to men independent of DSM-IV diagnosis. SLC6A4 methylation was further associated with the BSI-derived somatization dimension.

CONCLUSIONS

Female hypermethylation of a discrete region located within SLC6A4 promoter region could underlie differential SERT expression in women when compared to men and could be one of the causative mechanisms by which women exhibit increased prevalence of somatic symptoms.

摘要

背景

抑郁、焦虑和躯体形式障碍在女性中的患病率均高于男性。然而，导致这种性别差异的具体生物学机制尚不清楚。血清素能途径参与情绪和行为调节，因此被认为在几种精神障碍中发生改变。血清素转运体（SERT）由 SLC6A4 基因编码，由于其在血清素能传递中的关键作用而受到广泛关注。

方法

对 148 对同卵双胞胎受试者进行了以下评估：（i）根据 SCID-I 基于 DSM-IV 标准进行的终生分类诊断的焦虑-抑郁障碍；（ii）使用Brief Symptom Inventory（BSI）从维度方法评估当前的精神症状。使用 Infinium HumanMethylation450 对样本中的一部分进行了 SLC6A4 基因甲基化分析。在总样本中，使用焦磷酸测序技术进一步分析了 SLC6A4 基因启动子区域的 CpG 特异性甲基化。