Background
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.
Methods
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.
Results
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.
Conclusions
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.
Key Words
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Article info
Publication history
Published online: October 10, 2013
Accepted:
July 2,
2013
Received in revised form:
July 1,
2013
Received:
April 27,
2012
Identification
Copyright
© 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- The Emerging Role of Nucleus Accumbens Oxytocin in Social CognitionBiological PsychiatryVol. 76Issue 5
- PreviewThe 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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