Social stress and the oxytocin receptor gene interact to predict antisocial behavior in an at-risk cohort

Abstract

Polymorphisms in the oxytocin receptor gene (OXTR) are commonly associated with prosocial behaviors in the extant literature, yet their role in antisocial behaviors has rarely been explored, particularly during the transition from adolescence to early adulthood. We examined a prospective cohort (N=404), collecting youth, mother and clinician reports of conduct disordered and antisocial behavior at age 15 and 20. The oxytocin receptor rs53576 polymorphism was hypothesized to interact with social stress to predict antisocial outcomes. Structural equation modeling (SEM) results revealed a significant main effect at age 15 (p=.025); those with the G allele exhibited higher levels of conduct problems. SEM revealed a significant gene-by-environment interaction at age 20 (p=.029); those with the G allele who experienced high social stress exhibited higher levels of antisocial behavior. Heterozygous (AG) grouping models were compared and parameter estimations supported G dominant groupings. These novel findings suggest that rs53576 polymorphisms may influence social salience and contribute to risk for antisocial outcomes, particularly under conditions of high social stress.

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…Among G allele carriers this association was mediated by subjective ratings of interpersonal distrust. Support for this higher sensitivity to a dysfunctional or stressful social environment in rs53576 G allele carriers was further substantiated by both observational (Burkhouse et al, 2015; Dannlowski et al, 2015; Hostinar et al, 2014; Smearman et al, 2015; Sturge-Apple et al, 2012; Windle and Mrug, 2015) and experimental studies (Chen et al, 2011; McQuaid et al, 2015; Norman et al, 2012). As examples of observational studies, it could be shown that rs53576 GG homozygous subjects with ELS exposure have a smaller bilateral volume of the ventral striatum, a key structure of the dopaminergic nigrostriatal pathway (Dannlowski et al, 2015) which is implicated in both depression risk (Nestler and Carlezon, 2006) and parenting behavior (Strathearn et al, 2009).…”

Oxytocin and parent–child interaction in the development of empathy among children at risk for autism.

“…For instance, Sturge-Apple et al (2012) found evidence for increased susceptibility to interparental conflict on parental sensitivity among mothers with the GG genotype on OXTR rs53576. Similarly, G allele carriers had higher levels of antisocial behavior in the context of high social stress (Smearman et al, 2014), were more at risk for depressive symptoms when they had experienced high early adversity (McQuaid et al, 2013), and were more responsive to the effects of oxytocin inhalation (Marsh et al, 2012). …”

Stress and the social brain: behavioural effects and neurobiological mechanisms

“…Lower oxytocin concentrations have also been observed in the CSF 162 and plasma 163 of women with a history of childhood abuse and borderline personality disorder. Interestingly, although a particular variation in the gene encoding the oxytocin receptor is generally associated with increased prosocial behavior, when it interacts with developmental stress it is associated with increased levels of antisocial behaviors 164 .…”