The oxytocin receptor gene predicts brain activity during an emotion recognition task in autism

Florina Uzefovsky, Richard A.I. Bethlehem, Simone Shamay-Tsoory, Amber Ruigrok, Rosemary Holt, Michael Spencer, Lindsay Chura, Varun Warrier, Bhismadev Chakrabarti, Ed Bullmore, John Suckling, Dorothea Floris, Simon Baron-Cohen

Research output: Contribution to journalArticlepeer-review


Background: Autism is a highly varied and heritable neurodevelopmental condition, and common variants explain approximately 50% of the genetic variance of autism. One of the genes implicated in autism is the oxytocin receptor (OXTR). The current study combined genetic and brain imaging (fMRI) data to examine the moderating effect of genotype on the association between diagnosis and brain activity in response to a test of cognitive empathy. Methods: Participants were adolescents (mean age = 14.7 ± 1.7) who were genotyped for single nucleotide polymorphisms (SNPs) within the OXTR and underwent functional brain imaging while completing the adolescent version of the 'Reading the Mind in the Eyes' Test (Eyes Test). Results: Two (rs2254298, rs53576) of the five OXTR SNPs examined were significantly associated with brain activity during the Eyes Test, and three of the SNPs (rs2254298, rs53576, rs2268491) interacted with diagnostic status to predict brain activity. All of the effects localized to the right supramarginal gyrus (rSMG) and an overlap analysis revealed a large overlap of the effects. An exploratory analysis showed that activity within an anatomically defined rSMG and genotype can predict diagnostic status with reasonable accuracy. Conclusions: This is one of the first studies to investigate OXTR and brain function in autism. The findings suggest a neurogenetic mechanism by which OXTR-dependent activity within the rSMG is related to the aetiology of autism.

Original languageEnglish
Article number12
JournalMolecular Autism
Issue number1
StatePublished - 12 Mar 2019

Bibliographical note

Funding Information:
FU was supported by the Israel Science Foundation (grant no. 449/14), the British Friends of Haifa University, the British Friends of the Hebrew University and the Joseph Levy charitable foundation. MDS was supported by an MRC Clinician Scientist Fellowship from the UK Medical Research Council (G0701919). LRC was supported by the Gates Cambridge Scholarship Trust. RB was supported by the Pinsent Darwin Trust, Medical Research Council UK and Cambridge Trusts. AR was supported by the MRC and William Binks Autism Neuroscience Fellowship. SBC was supported by the MRC, Wellcome Trust, and the Autism Research Trust during the period of this work. The research was conducted in association with the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Publisher Copyright:
© 2019 The Author(s).


  • Autism
  • Imaging genetics
  • Oxytocin receptor
  • Supramarginal gyrus
  • fMRI

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Neuroscience
  • Developmental Biology
  • Psychiatry and Mental health


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