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Oxytocin Receptor Genotype Modulates Ventral Striatal Activity to Social Cues and Response to Stressful Life Events
Authors
,
Tobias Banaschewski
+34 more
Gareth J Barker
Arun L W Bokde
Ruediger Bruehl
Christian Büchel
Fabiana M Carvalho
Anna Cattrell
Patricia J Conrod
Sylvane Desrivières
Mira Fauth-Buehler
Jianfeng Feng
Herta Flor
Virgile Fritsch
Jürgen Gallinat
Hugh Garavan
Andreas Heinz
Tianye Jia
Claire Lawrence
Eva Loth
Anbarasu Lourdusamy
Karl Mann
Jean-Luc Martinot
Frauke Nees
Tomáš Paus
Zdenka Pausova
Jean-Baptiste Poline
Luise Poustka
Marcella Rietschel
Barbara Ruggeri
Gunter Schumann
Michael Smolka
David Stacey
Maren Struve
Chenyang Tao
Benjamin Thyreau
Publication date
8 October 2013
Publisher
'Elsevier BV'
Doi
Cite
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. © 2014 Society of Biological Psychiatry
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