Original ArticlesSpecificity of Familial Vulnerability for Alcoholism Versus Major Depression in MenLyons, Michael J. PhD*†‡; Schultz, Mark MS*; Neale, Michael PhD§; Brady, Kathleen MD, PhD∥; Eisen, Seth MD, MS¶#; Toomey, Rosemary PhD†‡; Rhein, Andrew PhD*; Faraone, Stephen PhD**; Tsuang, Ming MD, PhD†‡††Author Information *Department of Psychology, Boston University, Boston, Massachusetts; †Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, Massachusetts; ‡Harvard Medical School Department of Psychiatry at Massachusetts Mental Health Center, Boston, Massachusetts; §Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond, Virginia; ∥Tewksbury Hospital, Tewksbury, Massachusetts; ¶St. Louis VA Medical Center, Research and Medical Services, St. Louis, Missouri; #Washington University, Department of Internal Medicine, Division of General Medical Sciences, St. Louis, Missouri; **SUNY Upstate Medical University, Syracuse, New York; and ††Department of Psychiatry, University of California—San Diego, San Diego, California. Supported by a grant (DA04604) from the National Institute on Drug Abuse to Dr. Ming T. Tsuang and by the National Cancer Institute, Transdisciplinary Tobacco Use Research Center Grant, P50 CA84719, and by NIH grants MH-01458 and MH-65322 to M. C. Neale. Additional funding provided by the 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 VETR. Send reprint requests to Michael J. Lyons, PhD, Psychology Department, Boston University, 64 Cummington Street, Boston, MA 02215. The Journal of Nervous and Mental Disease: November 2006 - Volume 194 - Issue 11 - p 809-817 doi: 10.1097/01.nmd.0000244480.78431.49 Buy Metrics Abstract There are various hypotheses regarding comorbidity between alcohol dependence (AD) and major depression (MD). We interviewed 3372 pairs of male twins assessing DSM-III-R MD and AD. Individuals with comorbid MD and AD exhibited greater severity of each disorder than individuals with only one. MD in one twin was associated with risk of MD alone and MD plus AD, but not AD alone in the cotwin. AD in one twin was associated with risk of AD alone and AD plus MD, but not MD alone in the cotwin. The best fitting biometrical comorbidity model was the reciprocal causation model in which AD can cause MD and vice versa. However, a model in which genetic and environmental influences on each disorder were correlated could not be definitively rejected. Our data are most consistent with a mechanism of reciprocal causation, whereby MD increases risk for AD and AD increases risk of MD. © 2006 Lippincott Williams & Wilkins, Inc.