Schechter Daniel S, Moser Dominik A, Pointet Virginie C, Aue Tatjana, Stenz Ludwig, Paoloni-Giacobino Ariane, Adouan Wafae, Manini Aurélia, Suardi Francesca, Vital Marylene, Sancho Rossignol Ana, Cordero Maria I, Rothenberg Molly, Ansermet François, Rusconi Serpa Sandra, Dayer Alexandre G
Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Behav Brain Res. 2017 May 15;325(Pt B):268-277. doi: 10.1016/j.bbr.2016.10.009. Epub 2016 Oct 5.
Methylation of the serotonin 3A receptor gene (HTR3A) has been linked to child maltreatment and adult psychopathology. The present study examined whether HTR3A methylation might be associated with mothers' lifetime exposure to interpersonal violence (IPV), IPV-related psychopathology, child disturbance of attachment, and maternal neural activity.
Number of maternal lifetime IPV exposures and measures of maternal psychopathology including posttraumatic stress disorder (PTSD), major depression and aggressive behavior (AgB), and a measure of child attachment disturbance known as "secure base distortion" (SBD) were assessed in a sample of 35 mothers and children aged 12-42 months. Brain fMRI activation was assessed in mothers using 30-s silent film excerpts depicting menacing adult male-female interactions versus prosocial and neutral interactions. Group and continuous analyses were performed to test for associations between clinical and fMRI variables with DNA methylation.
Maternal IPV exposure-frequency was associated with maternal PTSD; and maternal IPV-PTSD was in turn associated with child SBD. Methylation status of several CpG sites in the HTR3A gene was associated with maternal IPV and IPV-PTSD severity, AgB and child SBD, in particular, self-endangering behavior. Methylation status at a specific CpG site (CpG2_III) was associated with decreased medial prefrontal cortical (mPFC) activity in response to film-stimuli of adult male-female interactions evocative of violence as compared to prosocial and neutral interactions.
Methylation status of the HTR3A gene in mothers is linked to maternal IPV-related psychopathology, trauma-induced brain activation patterns, and child attachment disturbance in the form of SBD during a sensitive period in the development of self-regulation.
血清素3A受体基因（HTR3A）的甲基化与儿童期受虐待及成人精神病理学有关。本研究探讨了HTR3A甲基化是否可能与母亲一生当中遭受的人际暴力（IPV）、与IPV相关的精神病理学、儿童依恋障碍以及母亲的神经活动有关。
在35对年龄在12至42个月的母亲和儿童样本中，评估了母亲一生当中遭受IPV的次数、母亲精神病理学指标，包括创伤后应激障碍（PTSD）、重度抑郁症和攻击行为（AgB），以及一种名为“安全基地扭曲”（SBD）的儿童依恋障碍指标。使用30秒的无声电影片段对母亲进行脑功能磁共振成像（fMRI）激活评估，这些片段描绘了威胁性的成年男女互动与亲社会和中性互动。进行了分组和连续分析，以检验临床和fMRI变量与DNA甲基化之间的关联。
母亲IPV暴露频率与母亲PTSD相关；而母亲IPV-PTSD又与儿童SBD相关。HTR3A基因中几个CpG位点的甲基化状态与母亲IPV及IPV-PTSD严重程度、AgB和儿童SBD相关，特别是自我伤害行为。与亲社会和中性互动相比，特定CpG位点（CpG2_III）的甲基化状态与内侧前额叶皮质（mPFC）在对唤起暴力的成年男女互动电影刺激的反应中活性降低有关。
母亲HTR3A基因的甲基化状态与母亲IPV相关的精神病理学、创伤诱导的脑激活模式以及自我调节发展敏感期内以SBD形式出现的儿童依恋障碍有关。
