The association between 2D:4D ratio and cognitive empathy is contingent on a common polymorphism in the oxytocin receptor gene (OXTR rs53576)

Omri Weisman, Kevin A. Pelphrey, James F. Leckman, Ruth Feldman, Yunfeng Lu, Anne Chong, Ying Chen, Mikhail Monakhov, Soo Hong Chew, Richard P. Ebstein

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Both testosterone and oxytocin influence an individual's accuracy in inferring another's feelings and emotions. Fetal testosterone, and the second-to-forth digit ratio (2D:4D) as its proxy, plays a role in social cognitive development, often by attenuating socio-affective skill. Conversely, oxytocin generally facilitates socio-affiliative and empathic cognition and behavior. A common polymorphism in the oxytocin receptor gene, OXTR rs53576, has been repeatedly linked with psychosocial competence, including empathy, with individuals homozygous for the G allele typically characterized by enhanced socio-cognitive skills compared to A allele carriers. We examined the role of oxytocin and testosterone in collectively contributing to individual differences in cognitive empathy as measured by Baron-Cohen's "Reading the Mind in the Eyes" task (RMET). Findings are based on a large cohort of male and female students (N= 1463) of Han Chinese ethnicity. In line with existing literature, women outperformed men in the RMET. Men showed significantly lower 2D:4D ratio compared to women, indicating higher exposure to testosterone during the prenatal period. Interestingly, variation in the OXTR gene was found to interact with 2D:4D to predict men's (but not women's) RMET performance. Among men with GG allelic variation, those with low fetal testosterone performed better on the RMET, compared to men with GG and high fetal testosterone, suggesting greater identification of another's emotional state. Taken together, our data lend unique support to the mutual influence of the oxytocin and testosterone systems in shaping core aspect of human social cognition early in development, further suggesting that this effect is gender-specific.

Original languageEnglish (US)
Pages (from-to)23-32
Number of pages10
StatePublished - Aug 1 2015
Externally publishedYes


  • 2D:4D
  • Empathy
  • Fetal estosterone
  • OXTR
  • Oxytocin
  • RMET
  • Social cognition

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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