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

Eva Loth 1 Jean-Baptiste Poline 2 Benjamin Thyreau 2 Tianye Jia 1 Chenyang Tao 3 Anbarasu Lourdusamy 1 David Stacey 1 Anna Cattrell 1 Sylvane Desrivières 1 Barbara Ruggeri 1 Virgile Fritsch 4 Tobias Banaschewski 5 Gareth J. Barker 1 Arun L. W. Bokde 6 Christian Büchel 7 Fabiana M. Carvalho 1 Patricia J. Conrod 1 Mira Fauth-Buehler 8 Herta Flor 8 Jürgen Gallinat 9 Hugh Garavan 6 Andreas Heinz 9 Ruediger Bruehl 10 Claire Lawrence 11 Karl Mann 12 Jean-Luc Martinot 13 Frauke Nees 8 Tomáš Paus 14 Zdenka Pausova 15 Luise Poustka 8 Marcella Rietschel 8 Michael N. Smolka 8 Maren Struve 16 Jianfeng Feng 17 Gunter Schumann 1
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.
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Submitted on : Wednesday, October 23, 2013 - 4:55:39 PM
Last modification on : Monday, December 13, 2021 - 9:16:05 AM

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Eva Loth, Jean-Baptiste Poline, Benjamin Thyreau, Tianye Jia, Chenyang Tao, et al.. Oxytocin Receptor Genotype Modulates Ventral Striatal Activity to Social Cues and Response to Stressful Life Events.. Biological Psychiatry, Elsevier, 2013, epub ahead of print. ⟨10.1016/j.biopsych.2013.07.043⟩. ⟨hal-00876111⟩



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