ADCYAP1R1 genotype, posttraumatic stress disorder, and depression among women exposed to childhood maltreatment

Monica Uddin, Shun Chiao Chang, Chao Zhang, Kerry Ressler, Kristina B. Mercer, Sandro Galea, Katherine M. Keyes, Katie A. McLaughlin, Derek E. Wildman, Allison E. Aiello, Karestan C. Koenen

Research output: Contribution to journalArticlepeer-review


Background A growing literature indicates that genetic variation, in combination with adverse early life experiences, shapes risk for later mental illness. Recent work also suggests that molecular variation at the ADCYAP1R1 locus is associated with posttraumatic stress disorder (PTSD) in women. We sought to test whether childhood maltreatment (CM) interacts with ADCYAP1R1 genotype to predict PTSD in women. Methods Data were obtained from 495 adult female participants from the Detroit Neighborhood Health Study. Genotyping of rs2267735, an ADCYAP1R1 variant, was conducted via TaqMan assay. PTSD, depression, and CM exposure were assessed via structured interviews. Main and interacting effects of ADCYAP1R1 and CM levels on past month PTSD and posttraumatic stress (PTS) severity were examined using logistic regression and a general linear model, respectively. As a secondary analysis, we also assessed main and interacting effects of ADCYAP1R1 and CM variation on risk of past-month depression diagnosis and symptom severity. Results No significant main effects were observed for ADCYAP1R1 genotype on either PTSD/PTS severity. In contrast, a significant ADCYAP1R1 × CM interaction was observed for both past month PTSD and PTS severity, with carriers of the "C" allele showing enhanced risk for these outcomes among women exposed to CM. No significant main or interaction effects were observed for past month depression/depression severity. Conclusions Genetic variation at the ADCYAP1R1 locus interacts with CM to shape risk of later PTSD, but not depression, among women. The molecular mechanisms contributing to this interaction require further investigation.

Original languageEnglish (US)
Pages (from-to)251-258
Number of pages8
JournalDepression and Anxiety
Issue number3
StatePublished - Mar 2013
Externally publishedYes


  • PTSD
  • candidate gene
  • childhood maltreatment
  • depression
  • gene-environment interaction
  • replication

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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