Xulu Khethelo R, Womersley Jacqueline S, Sommer Jessica, Hinsberger Martina, Elbert Thomas, Weierstall Roland, Kaminer Debbie, Malan-Müller Stefanie, Seedat Soraya, Hemmings Sian M J
Department of Psychiatry, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa.
Department of Psychiatry, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council / Stellenbosch University Genomics of Brain Disorders Research Unit, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa.
Psychiatry Res. 2021 Jan;295:113608. doi: 10.1016/j.psychres.2020.113608. Epub 2020 Nov 27.
Exposure to violence can lead to appetitive aggression (AA), the positive feeling and fascination associated with violence, and posttraumatic stress disorder (PTSD), characterised by hyperarousal, reexperience and feelings of ongoing threat. Psychotherapeutic interventions may act via DNA methylation, an environmentally sensitive epigenetic mechanism that can influence gene expression. We investigated epigenetic signatures of psychotherapy for PTSD and AA symptoms in South African men with chronic trauma exposure. Participants were assigned to one of three groups: narrative exposure therapy for forensic offender rehabilitation (FORNET), cognitive behavioural therapy or waiting list control (n = 9-10/group). Participants provided saliva and completed the Appetitive Aggression Scale and PTSD Symptom Severity Index at baseline, 8-month and 16-month follow-up. The relationship, over time, between methylation in 22 gene promoter region sites, symptom scores, and treatment was assessed using linear mixed models. Compared to baseline, PTSD and AA symptom severity were significantly reduced at 8 and 16 months, respectively, in the FORNET group. Increased methylation of genes implicated in dopaminergic neurotransmission (NR4A2) and synaptic plasticity (AUTS2) was associated with reduced PTSD symptom severity in participants receiving FORNET. Analyses across participants revealed a proportional relationship between AA and methylation of TFAM, a gene involved in mitochondrial biosynthesis.
接触暴力会导致欲求性攻击（AA），即与暴力相关的积极感受和迷恋，以及创伤后应激障碍（PTSD），其特征为过度警觉、反复体验和持续的威胁感。心理治疗干预可能通过DNA甲基化起作用，DNA甲基化是一种对环境敏感的表观遗传机制，可影响基因表达。我们调查了针对有慢性创伤暴露经历的南非男性PTSD和AA症状的心理治疗的表观遗传特征。参与者被分配到三组之一：用于法医罪犯康复的叙事暴露疗法（FORNET）、认知行为疗法或等待名单对照组（每组n = 9 - 10）。参与者在基线、8个月和16个月随访时提供唾液，并完成欲求性攻击量表和PTSD症状严重程度指数。使用线性混合模型评估22个基因启动子区域位点的甲基化、症状评分和治疗之间随时间的关系。与基线相比，FORNET组的PTSD和AA症状严重程度在8个月和16个月时分别显著降低。在接受FORNET治疗的参与者中，与多巴胺能神经传递（NR4A2）和突触可塑性（AUTS2）相关的基因甲基化增加与PTSD症状严重程度降低有关。对所有参与者的分析揭示了AA与TFAM（一种参与线粒体生物合成的基因）甲基化之间的比例关系。
