Psychological Medicine

Original Articles

Co-morbid major depression and generalized anxiety disorders in the National Comorbidity Survey follow-up

R. C. Kesslera1 c1, M. Grubera1, J. M. Hettemaa2, I. Hwanga1, N. Sampsona1 and K. A. Yonkersa3

a1 Department of Health Care Policy, Harvard Medical School, Boston, MA, USA

a2 Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

a3 Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA


Background Although generalized anxiety disorder (GAD) and major depressive episode (MDE) are known to be highly co-morbid, little prospective research has examined whether these two disorders predict the subsequent first onset or persistence of the other or the extent to which other predictors explain the time-lagged associations between GAD and MDE.

Method Data were analyzed from the nationally representative two-wave panel sample of 5001 respondents who participated in the 1990–1992 National Comorbidity Survey (NCS) and the 2001–2003 NCS follow-up survey. Both surveys assessed GAD and MDE. The baseline NCS also assessed three sets of risk factors that are considered here: childhood adversities, parental history of mental-substance disorders, and respondent personality.

Results Baseline MDE significantly predicted subsequent GAD onset but not persistence. Baseline GAD significantly predicted subsequent MDE onset and persistence. The associations of each disorder with the subsequent onset of the other attenuated with time since onset of the temporally primary disorder, but remained significant for over a decade after this onset. The risk factors predicted onset more than persistence. Meaningful variation was found in the strength and consistency of associations between risk factors and the two disorders. Controls for risk factors did not substantially reduce the net cross-lagged associations of the disorders with each other.

Conclusions The existence of differences in risk factors for GAD and MDE argues against the view that the two disorders are merely different manifestations of a single underlying internalizing syndrome or that GAD is merely a prodrome, residual, or severity marker of MDE.

(Received June 04 2007)

(Revised August 30 2007)

(Accepted September 08 2007)

(Online publication November 30 2007)


c1 Address for correspondence: R. C. Kessler, Ph.D., Department of Health Care Policy, Harvard Medical School, 180 Longwood Avenue, Boston MA 02115, USA. (Email: