Oxytocin receptor genotype modulates ventral striatal activity to social cues and response to stressful life events

Eva Loth, Jean Baptiste Poline, Benjamin Thyreau, Tianye Jia, Chenyang Tao, Anbarasu Lourdusamy, David Stacey, Anna Cattrell, Sylvane Desrivières, Barbara Ruggeri, Virgile Fritsch, Tobias Banaschewski, Gareth J. Barker, Arun L.W. Bokde, Christian Büchel, Fabiana M. Carvalho, Patricia J. Conrod, Mira Fauth-Buehler, Herta Flor, Jürgen GallinatHugh Garavan, Andreas Heinz, Ruediger Bruehl, Claire Lawrence, Karl Mann, Jean Luc Martinot, Frauke Nees, Tomáš Paus, Zdenka Pausova, Luise Poustka, Marcella Rietschel, Michael Smolka, Maren Struve, Jianfeng Feng, Gunter Schumann

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)367-376
Number of pages10
JournalBiological Psychiatry
Volume76
Issue number5
DOIs
Publication statusPublished - 2014 Sep 1
Externally publishedYes

Keywords

  • Amygdala
  • functional magnetic resonance imaging
  • genetics
  • oxytocin
  • social behavior
  • ventral striatum

ASJC Scopus subject areas

  • Biological Psychiatry

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