title: A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic-limbic structure and function.
abstract: The evolutionarily highly conserved neuropeptide oxytocin is a key mediator of social and emotional behavior in mammals, including humans. A common variant (rs53576) in the oxytocin receptor gene (OXTR) has been implicated in social-behavioral phenotypes, such as maternal sensitivity and empathy, and with neuropsychiatric disorders associated with social impairment, but the intermediate neural mechanisms are unknown. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to identify structural and functional alterations in OXTR risk allele carriers and their link to temperament. Activation and interregional coupling of the amygdala during the processing of emotionally salient social cues was significantly affected by genotype. In addition, evidence for structural alterations in key oxytocinergic regions emerged, particularly in the hypothalamus. These neural characteristics predicted lower levels of reward dependence, specifically in male risk allele carriers. Our findings identify sex-dependent mechanisms impacting the structure and function of hypothalamic-limbic circuits that are of potential clinical and translational significance.
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. tosth@mail.nih.gov
authors.forename: Heike
authors.initials: H
authors.lastname: Tost
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kolachana
authors.forename: Shabnam
authors.initials: S
authors.lastname: Hakimi
authors.forename: Herve
authors.initials: H
authors.lastname: Lemaitre
authors.forename: Beth A
authors.initials: BA
authors.lastname: Verchinski
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Mattay
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
mesh_terms: D000328:Adult; D000483:Alleles; D001931:Brain Mapping; D004644:Emotions; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology*; D008297:Male; D018045:Receptors, Oxytocin / Q000235:genetics*; D012727:Sex Characteristics; D012919:Social Behavior; D013694:Temperament
chemical_list: D018045:Receptors, Oxytocin