(2014) Oxytocin receptor genotype modulates ventral striatal activity to social cues and response to stressful life events. Biological Psychiatry, 76 (5). pp. 367-376. doi:10.1016/j.biopsych.2013.07.043

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Abstract

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.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions:	Faculty of Science > Computer Science
Library of Congress Subject Headings (LCSH):	Oxytocin, Genetics, Magnetic resonance imaging, Amygdaloid body, Interpersonal relations, Autism spectrum disorders -- Research, Anxiety disorders -- Research, Depression, Mental -- Research, Teenagers -- Medicine
Journal or Publication Title:	Biological Psychiatry
Publisher:	Elsevier
ISSN:	0006-3223
Official Date:	1 September 2014
Dates:	Date Event 1 September 2014 Published 8 October 2013 Available 2 July 2013 Accepted 27 April 2012 Submitted
Date of first compliant deposit:	3 March 2016
Volume:	76
Number:	5
Page Range:	pp. 367-376
DOI:	10.1016/j.biopsych.2013.07.043
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Sixth Framework Programme (European Commission) (FP6), Seventh Framework Programme (European Commission) (FP7), Germany. Bundesministerium für Bildung und Forschung (BMBF), Sweden. Vetenskapsrådet [Research Council], National Institute for Health Research (Great Britain) (NIHR)
Grant number:	LSHM-CT-2007-037286 (FP6), 242257 (FP7), 01EV0711 (BMBF), EU-AIMS 115300-2 (Vetenskapsrådet), 93558 (NIHR)
Embodied As:	1

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