Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study

Lauren M. Sippel, Shizhong Han, Laura E. Watkins, Ilan Harpaz-Rotem, Steven M. Southwick, John H. Krystal, Miranda Olff, Richard Sherva, Lindsay A. Farrer, Henry R. Kranzler, Joel Gelernter, Robert H. Pietrzak

Research output: Contribution to journalArticlepeer-review


The human oxytocin system is implicated in social behavior and stress recovery. Polymorphisms in the oxytocin receptor gene (OXTR) may interact with attachment style to predict stress-related psychopathology like posttraumatic stress disorder (PTSD). The objective of this study was to examine independent and interactive effects of the OXTR single nucleotide polymorphism (SNP) rs53576, which has been associated with stress reactivity, support-seeking, and PTSD in prior studies, and attachment style on risk for PTSD in a nationally representative sample of 2163 European-American (EA) U.S. military veterans who participated in two independent waves of the National Health and Resilience in Veterans Study (NHRVS). Results revealed that insecure attachment style [adjusted odds ratio (OR) = 4.29; p < 0.001] and the interaction of rs53576 and attachment style (OR = 2.58, p = 0.02) were associated with probable lifetime PTSD. Among individuals with the minor A allele, the prevalence of probable PTSD was significantly higher among those with an insecure attachment style (23.9%) than those with a secure attachment style (2.0%), equivalent to an adjusted OR of 10.7. We attempted to replicate these findings by utilizing dense marker data from a genome-wide association study of 2215 high-risk civilians; one OXTR variant, though not rs53576, was associated with PTSD. Exploratory analyses in the veteran sample revealed that the interaction between this variant and attachment style predicting probable PTSD approached statistical significance. Results indicate that polymorphisms in the OXTR gene and attachment style may contribute to vulnerability to PTSD in U.S. military veterans.

Original languageEnglish (US)
Pages (from-to)139-147
Number of pages9
JournalJournal of Psychiatric Research
StatePublished - Nov 2017
Externally publishedYes


  • Gene environment interaction
  • Insecure attachment
  • OXTR
  • Posttraumatic stress disorder
  • rs53576

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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