Affiliation buffers stress: cumulative genetic risk in oxytocin-vasopressin genes combines with early caregiving to predict PTSD in war-exposed young children
Affiliation buffers stress: cumulative genetic risk in oxytocin-vasopressin genes combines with early caregiving to predict PTSD in war-exposed young children
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DOI：
10.1038/tp.2014.6
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发表时间：
2014-03-01
影响因子：
6.8
通讯作者：
Ebstein, R. P.
中科院分区：
文献类型：
--
作者：
Feldman, R.;Vengrober, A.;Ebstein, R. P.
研究表明，创伤后应激障碍（PTSD）的风险是由遗传脆弱性和早期经历之间的相互作用形成的;然而，早期经历通常是通过成年人的回顾性描述来评估的。在这里，我们采用了一个前瞻性的纵向设计，结合实时观察的早期抑郁症的遗传易感性评估沿着轴的加压素-催产素（OT）基因通路，以测试G × E的PTSD的贡献。参与者是232名以色列儿童（1.5-5岁）及其父母，其中148人生活在持续战争地区，84人生活在控制区。通过将先前与精神病理学、社会性和行为相关的三个基因（OXTR、CD 38和AVPR 1a）中的五个风险等位基因相加，计算每个家庭成员的累积遗传风险因子。儿童创伤后应激障碍的诊断和母亲与孩子的互动，在多种情况下观察。在儿童中期（7-8岁），重新评估儿童精神病理学。战争暴露使Axis-I障碍的倾向增加了三倍：60%的暴露儿童在童年中期表现出精神障碍，62%的儿童表现出几种共病障碍。另一方面，母亲敏感的支持降低了精神病理学的风险。发现儿童遗传风险的G × E效应：在战争暴露的背景下，加压素-OT通路上更大的遗传风险增加了精神病理学的倾向。在暴露的儿童中，PTSD从早期到中期的慢性化与儿童、母亲和父亲的遗传风险较高、母亲支持较低和初始回避症状较大有关。母亲的支持和减少母子互惠预测儿童回避。这些发现强调了人类关系系统的遗传和行为方面在塑造创伤后应激障碍的脆弱性以及提供创伤后恢复力的潜在机制方面的显着性。
Research indicates that risk for post-traumatic stress disorder (PTSD) is shaped by the interaction between genetic vulnerability and early caregiving experiences; yet, caregiving has typically been assessed by adult retrospective accounts. Here, we employed a prospective longitudinal design with real-time observations of early caregiving combined with assessment of genetic liability along the axis of vasopressin-oxytocin (OT) gene pathways to test G x E contributions to PTSD. Participants were 232 young Israeli children (1.5-5 years) and their parents, including 148 living in zones of continuous war and 84 controls. A cumulative genetic risk factor was computed for each family member by summing five risk alleles across three genes (OXTR, CD38 and AVPR1a) previously associated with psychopathology, sociality and caregiving. Child PTSD was diagnosed and mother-child interactions were observed in multiple contexts. In middle childhood (7-8 years), child psychopathology was re-evaluated. War exposure increased propensity to develop Axis-I disorder by threefold: 60% of exposed children displayed a psychiatric disorder by middle childhood and 62% of those showed several comorbid disorders. On the other hand, maternal sensitive support reduced risk for psychopathology. G x E effect was found for child genetic risk: in the context of war exposure, greater genetic risk on the vasopressin-OT pathway increased propensity for psychopathology. Among exposed children, chronicity of PTSD from early to middle childhood was related to higher child, maternal and paternal genetic risk, low maternal support and greater initial avoidance symptoms. Child avoidance was predicted by low maternal support and reduced mother-child reciprocity. These findings underscore the saliency of both genetic and behavioral facets of the human affiliation system in shaping vulnerability to PTSD as well as providing an underlying mechanism of post-traumatic resilience.