title: Oxytocin receptor genotype modulates ventral striatal activity to social cues and response to stressful life events.
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.
authors.affiliation: Institute of Psychiatry, King's College London; MRC Social, Genetic and Developmental Psychiatry Centre, London. Electronic address: eva.loth@kcl.ac.uk.
authors.forename: Eva
authors.initials: E
authors.lastname: Loth
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Poline
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Thyreau
authors.affiliation: Institute of Psychiatry, King's College London; MRC Social, Genetic and Developmental Psychiatry Centre, London.
authors.forename: Tianye
authors.initials: T
authors.lastname: Jia
authors.affiliation: Center for Computational Systems Biology, School of Mathematical Science, Fudan University, Shanghai, China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Tao
authors.affiliation: Institute of Psychiatry, King's College London; MRC Social, Genetic and Developmental Psychiatry Centre, London.
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Lourdusamy
authors.affiliation: Institute of Psychiatry, King's College London; MRC Social, Genetic and Developmental Psychiatry Centre, London.
authors.forename: David
authors.initials: D
authors.lastname: Stacey
authors.affiliation: Institute of Psychiatry, King's College London; MRC Social, Genetic and Developmental Psychiatry Centre, London.
authors.forename: Anna
authors.initials: A
authors.lastname: Cattrell
authors.affiliation: Institute of Psychiatry, King's College London; MRC Social, Genetic and Developmental Psychiatry Centre, London.
authors.forename: Sylvane
authors.initials: S
authors.lastname: Desrivières
authors.affiliation: Institute of Psychiatry, King's College London; MRC Social, Genetic and Developmental Psychiatry Centre, London.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruggeri
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center.
authors.forename: Virgile
authors.initials: V
authors.lastname: Fritsch
authors.affiliation: Central Institute of Mental Health, University of Mannheim.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Institute of Psychiatry, King's College London.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Institute of Neuroscience , Trinity College, Dublin, Ireland.
authors.forename: Arun L W
authors.initials: AL
authors.lastname: Bokde
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Hamburg.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: Institute of Psychiatry, King's College London; MRC Social, Genetic and Developmental Psychiatry Centre, London.
authors.forename: Fabiana M
authors.initials: FM
authors.lastname: Carvalho
authors.affiliation: Institute of Psychiatry, King's College London; Department of Psychiatry , Université de Montreal, CHU St Justine Hosptial.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Conrod
authors.affiliation: Central Institute of Mental Health, University of Mannheim.
authors.forename: Mira
authors.initials: M
authors.lastname: Fauth-Buehler
authors.affiliation: Central Institute of Mental Health, University of Mannheim.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Institute of Neuroscience , Trinity College, Dublin, Ireland; Departments of Psychiatry and Psychology, University of Vermont, Burlington, Vermont.
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Physikalisch-Technische Bundesanstalt, Braunschweig und Berlin.
authors.forename: Ruediger
authors.initials: R
authors.lastname: Bruehl
authors.affiliation: School of Psychology, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Lawrence
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Department of Addictive Behaviour and Addiction Medicine, Mannheim.
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 "Imaging and Psychiatry," University Paris Sud, Orsay, and AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
authors.affiliation: Central Institute of Mental Health, University of Mannheim.
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.affiliation: School of Psychology, University of Nottingham, Nottingham, United Kingdom; The Rotman Research Institute, Baycrest; Montreal Neurological Institute, McGill University, Montreal.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Paus
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
authors.affiliation: Central Institute of Mental Health, University of Mannheim.
authors.forename: Luise
authors.initials: L
authors.lastname: Poustka
authors.affiliation: Central Institute of Mental Health, University of Mannheim.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Central Institute of Mental Health, University of Mannheim.
authors.forename: Michael
authors.initials: M
authors.lastname: Smolka
authors.affiliation: Department of Psychiatry and Psychotherapy; Neuroimaging Center, Department of Psychology, Technische Universität Dresden, Dresden, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Struve
authors.affiliation: Department of Computer Science, University of Warwick, Coventry, United Kingdom.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Feng
authors.affiliation: Institute of Psychiatry, King's College London.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000502:physiology; D002648:Child; D003342:Corpus Striatum / Q000502:physiology*; D003463:Cues; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008016:Life Change Events; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics*; D012815:Signal Processing, Computer-Assisted; D012919:Social Behavior; D044465:White People / Q000235:genetics
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin; D010100:Oxygen
keywords: Amygdala; functional magnetic resonance imaging; genetics; oxytocin; social behavior; ventral striatum