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

TY - JOUR

T1 - Oxytocin Receptor Genotype Modulates Ventral Striatal Activity to Social Cues and Response to Stressful Life Events

AU - Loth, Eva

AU - Poline, Jean-Baptiste

AU - Thyreau, Benjamin

AU - Jia, Tianye

AU - Tao, Chenyang

AU - Lourdusamy, Anbarasu

AU - Stacey, David

AU - Cattrell, Anna

AU - Desrivières, Sylvane

AU - Ruggeri, Barbara

AU - Fritsch, Virgile

AU - Banaschewski, Tobias

AU - Barker, Gareth J

AU - Bokde, Arun L W

AU - Büchel, Christian

AU - Carvalho, Fabiana M

AU - Conrod, Patricia J

AU - Fauth-Buehler, Mira

AU - Flor, Herta

AU - Gallinat, Jürgen

AU - Garavan, Hugh

AU - Heinz, Andreas

AU - Bruehl, Ruediger

AU - Lawrence, Claire

AU - Mann, Karl

AU - Martinot, Jean-Luc

AU - Nees, Frauke

AU - Paus, Tomáš

AU - Pausova, Zdenka

AU - Poustka, Luise

AU - Rietschel, Marcella

AU - Smolka, Michael

AU - Struve, Maren

AU - Feng, Jianfeng

AU - Schumann, Gunter

AU - IMAGEN Consortium

N1 - © 2013 Society of Biological Psychiatry.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1016/j.biopsych.2013.07.043

DO - 10.1016/j.biopsych.2013.07.043

M3 - SCORING: Journal article

C2 - 24120094

VL - 76

SP - 367

EP - 376

JO - BIOL PSYCHIAT

JF - BIOL PSYCHIAT

SN - 0006-3223

IS - 5

ER -