Affiliation buffers stress: cumulative genetic risk in oxytocin–vasopressin genes combines with early caregiving to predict PTSD in war-exposed young children

R Feldman,A Vengrober,R P Ebstein

doi:10.1038/tp.2014.6

Abstract

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 × 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 × 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.

Highlights

We examined the role of the human affiliation system in posttraumatic stress disorder (PTSD) and calculated a cumulative risk index for each family member by combining five risk alleles on the Oxytocin receptor (OXTR), CD38 and AVPR1a genes previously linked with social and attachment deficits.[16,18]
Our study, among the first to follow trauma-exposed children from infancy to middle childhood, indicates that lengthy exposure to war-related trauma increased the prevalence of child psychopathology by threefold: 60% of children growing up in zones of continuous political violence received an Axis-I diagnosis by middle childhood and 62% of those diagnosed had more than one disorder
Our findings are first to demonstrate the involvement of both biological (OT–vasopressin genotype) and behavioral facets of the human affiliative system in contributing to differential sensitivity to developing PTSD

Summary

Introduction

Especially when lengthy, repeated and potentially lethal, contributes to the development of posttraumatic stress disorder (PTSD) in some individuals but not in others and identifying those with greater vulnerability or resilience is among the central goals of PTSD research.[1,2,3] Repeated exposure to traumatic events during the first years of life, when critical brain structures are maturing, carries an even greater risk for psychopathology.[4,5,6] Research has demonstrated genetic involvement in PTSD and suggests that similar to most complex behavioral disorders, risk for PTSD is likely determined by the interaction of genetic dispositions and early caregiving experiences.[7,8,9,10,11] Yet, characterization of the early environment has been poorly assessed and typically relies on adult recollection of caregiving, accounts often colored by current mental state. To move the study of G × E interaction in the etiology of PTSD forward, there is a need to integrate features of the rearing environment with genetic vulnerability focused on key neurobiological systems that underpin affiliative and attachment behavior. Such research may be most fruitful if conducted prospectively beginning in early childhood and combining real-time assessments of parenting with genetic biomarkers of parents and child

Methods

Results

Conclusion