Archival Report| Volume 76, ISSUE 5, P367-376, September 01, 2014

Oxytocin Receptor Genotype Modulates Ventral Striatal Activity to Social Cues and Response to Stressful Life Events


      Common variants in the oxytocin receptor gene (OXTR) have been shown to influence social and affective behavior and to moderate the effect of adverse experiences on risk for social-affective problems. However, the intermediate neurobiological mechanisms are not fully understood. Although human functional neuroimaging studies have reported that oxytocin effects on social behavior and emotional states are mediated by amygdala function, animal models indicate that oxytocin receptors in the ventral striatum (VS) modulate sensitivity to social reinforcers. This study aimed to comprehensively investigate OXTR-dependent brain mechanisms associated with social-affective problems.


      In a sample of 1445 adolescents we tested the effect of 23-tagging single nucleotide polymorphisms across the OXTR region and stressful life events (SLEs) on functional magnetic resonance imaging blood oxygen level–dependent activity in the VS and amygdala to animated angry faces. Single nucleotide polymorphisms for which gene-wide significant effects on brain function were found were then carried forward to examine associations with social-affective problems.


      A gene-wide significant effect of rs237915 showed that adolescents with minor CC-genotype had significantly lower VS activity than CT/TT-carriers. Significant or nominally significant gene × environment effects on emotional problems (in girls) and peer problems (in boys) revealed a strong increase in clinical symptoms as a function of SLEs in CT/TT-carriers but not CC-homozygotes. However, in low-SLE environments, CC-homozygotes had more emotional problems (girls) and peer problems (boys). Moreover, among CC-homozygotes, reduced VS activity was related to more peer problems.


      These findings suggest that a common OXTR-variant affects brain responsiveness to negative social cues and that in “risk-carriers” reduced sensitivity is simultaneously associated with more social-affective problems in “favorable environments” and greater resilience against stressful experiences.

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      Linked Article

      • The Emerging Role of Nucleus Accumbens Oxytocin in Social Cognition
        Biological PsychiatryVol. 76Issue 5
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          The nucleus accumbens (NAc), also known as the ventral striatum, is a key node of the mesocorticolimbic reward system. This circuit has received great attention because of its role in the pathophysiology of addiction and depression. However, it likely evolved to motivate behaviors that were important for survival, reproduction, and fitness. Increasing evidence suggests that adaptive social behaviors in a wide diversity of species are also reinforced by this system. The evolutionary persistence of these behaviors might require this reinforcement, particularly in cases where individual benefit and group benefit are in conflict.
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