Common genetic liability to major depression and posttraumatic stress disorder in men☆
Received 4 January 2007; received in revised form 16 April 2007; accepted 24 April 2007.
Abstract
Background
Major depression (MD) and posttraumatic stress disorder (PTSD) are highly comorbid. The degree to which a common genetic liability explains the etiology of the MD-PTSD association has not been quantified and has important implications for research and prevention.
Methods
This paper presents an analysis of data from 6744 members of the Vietnam Era Twin Registry. MD and PTSD were assessed using the Diagnostic Interview Schedule-III-R in 1991–92. Bivariate twin modeling was conducted to determine the genetic and environmental etiology of the MD-PTSD association.
Results
The best-fitting model for the MD-PTSD association included a substantial genetic correlation (r=.77; 95% CI, .50–1.00) and a modest individual-specific environmental correlation (r=.34; 95% CI, .19–.48). Common genetic liability explained 62.5% of MD-PTSD comorbidity. Genetic influences common to MD explained 15% of the total variance in risk for PTSD and 58% of the genetic variance in PTSD. Individual-specific environmental influences common to MD explained only 11% of the individual-specific environmental variance in PTSD.
Limitations
Our participants were male Vietnam era veterans and our findings may not generalize to civilians, females or other cohorts.
Conclusions
MD-PTSD comorbidity is largely explained by common genetic influences. Substantial genetic overlap between MD and PTSD implies that genes implicated in the etiology of MD are strong candidates for PTSD and vice versa. Environmental influences on MD and PTSD explain less of their covariation and appear to be largely disorder-specific. Research is needed to identify environmental factors that influence the development of MD versus PTSD in the context of common genetic liability.
aDepartment of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA, United States
bDepartment of Epidemiology, Harvard School of Public Health, Boston, MA, United States
cDepartment of Psychiatry, Boston University School of Medicine, United States
dDepartment of Community Health, St. Louis University School of Public Health, St. Louis, MO, United States
eDepartment of Psychology, Boston University, Boston, MA, United States
fHarvard Institute of Psychiatric Epidemiology and Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States
gDepartment of Psychiatry, Harvard Medical School at Massachusetts Mental Health Center, Boston, MA, United States
hDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United States
iResearch and Medical Service, St. Louis VAMC, St. Louis, MO, United States
jSeattle VA ERIC/Vietnam Era Twin Registry, Seattle, Washington, United States
kDepartment of Epidemiology, University of Washington, Seattle, Washington, United States
lUniversity of California Medical School in San Diego, San Diego, CA, United States
Corresponding author. Karestan C. Koenen, Department of Society, Human Development, and Health, Harvard School of Public Health, 677 Huntington Avenue, Kresge 613, Boston MA, 02115, United States. Tel.: +1 617 432 4622; fax: +1 617 432 3755.
☆ Conflict of interest: All authors declare they have no conflict of interest
Contributors: Dr. Koenen conceptualized the research question, conducted the literature review, performed statistical analyses, and took the lead role in writing the first draft of the paper. Drs. Fu and Ertel participated in the conceptualization of the research question, statistical analyses, and in editing the paper for important intellectual content. Drs. Lyons, Eisen, True, Goldberg, and Tsuang designed the study, developed the protocol for data collection, and edited the paper for important intellectual content. All authors contributed to and have approved the final manuscript.
Funding sources: Funding for this study was provided by NIMH-K08MH070627 to Dr. Koenen and NCI-K07CA104119 to Dr. Fu. Additional funding was provided by the American Foundation for Suicide Prevention, National Institute on Drug Abuse and the Robert Wood Johnson Foundation. The United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry.
The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
ABSTRACT