ADCYAP1R1 Genotype, Posttraumatic Stress Disorder, and Depression Among Women Exposed to Childhood Maltreatment

• Type of Material: Article
• Authors: Monica Uddin, Wayne State University; Shun-Chiao Chang, Harvard University; Chao Zhang, Wayne State University; Kerry Ressler, Emory University; Kristina B. Mercer, Emory University; Sandro Galea, Columbia University; Katherine M. Keyes, Columbia University; Katie A. McLaughlin, Harvard University; Derek E. Wildman, Wayne State University; Allison E. Aiello, University of Michigan; Karestan C. Koenen, Columbia University
• Language: English
• Date: 2013-03-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/da.22037
• Title of Journal or Parent Work: Depression and Anxiety
• ISSN: 1091-4269
• Volume: 30
• Issue: 3
• Start Page: 251
• End Page: 258
• Grant/Funding Information: This study was supported by National Institutes of Health Grants DA022720; DA022720-S1; MH092526; MH088283; MH078928; and MH093612.
• Keywords: ABUSE; candidate gene; LIFE EVENTS; Social Sciences; PACAP; Science & Technology; COMMUNITY; Life Sciences & Biomedicine; replication; RISK; NEUROTROPHIC FACTOR; CYCLASE-ACTIVATING POLYPEPTIDE; VICTIMIZATION; depression; childhood maltreatment; EXPRESSION; PTSD; Psychology, Clinical; ADULT RECOLLECTIONS; Psychology; gene-environment interaction; Psychiatry
• Research Categories: Health Sciences, Mental Health; Psychology, Clinical; Biology, Genetics

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.