Adcyap1r1 genotype, posttraumatic stress disorder, and depression among women exposed to childhood maltreatment

Depress Anxiety. 2013 Mar;30(3):251-8. doi: 10.1002/da.22037. Epub 2012 Dec 28.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child Abuse / psychology*
  • Depression / diagnosis
  • Depression / etiology*
  • Depression / genetics
  • Female
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Predisposition to Disease / psychology
  • Genotype
  • Humans
  • Middle Aged
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / genetics*
  • Risk Factors
  • Stress Disorders, Post-Traumatic / diagnosis
  • Stress Disorders, Post-Traumatic / etiology*
  • Stress Disorders, Post-Traumatic / genetics
  • Young Adult

Substances

  • ADCYAP1R1 protein, human
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I