Skip to main content
    • Aa
    • Aa

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

  • R. C. Kessler (a1), M. Gruber (a1), J. M. Hettema (a2), I. Hwang (a1), N. Sampson (a1) and K. A. Yonkers (a3)...

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.


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.


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.


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.

Corresponding author
*Address for correspondence: R. C. Kessler, Ph.D., Department of Health Care Policy, Harvard Medical School, 180 Longwood Avenue, Boston MA 02115, USA. (Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

RF Belli (1998). The structure of autobiographical memory and the event history calendar: potential improvements in the quality of retrospective reports in surveys. Memory 6, 383406.

RF Belli , WL Shay , FP Stafford (2001). Event history calendars and question list surveys: a direct comparison of interviewing methods. Public Opinion Quarterly 65, 4574.

K Belzer , FR Schneier (2004). Comorbidity of anxiety and depressive disorders: issues in conceptualization, assessment, and treatment. Journal of Psychiatric Practice 10, 296306.

N Breslau (1985). Depressive symptoms, major depression, and generalized anxiety: a comparison of self-reports on CES-D and results from diagnostic interviews. Psychiatry Research 15, 219229.

N Breslau , GC Davis (1985 a). DSM-III generalized anxiety disorder: an empirical investigation of more stringent criteria. Psychiatry Research 15, 231238.

N Breslau , GC Davis (1985 b). Further evidence on the doubtful validity of generalized anxiety disorder. Psychiatry Research 16, 177179.

TA Brown , BF Chorpita , DH Barlow (1998). Structural relationships among dimensions of the DSM-IV anxiety and mood disorders and dimensions of negative affect, positive affect, and autonomic arousal. Journal of Abnormal Psychology 107, 179192.

RC Durham , T Allan , CA Hackett (1997). On predicting improvement and relapse in generalized anxiety disorder following psychotherapy. British Journal of Clinical Psychology 36, 101119.

B Efron (1988). Logistic regression, survival analysis, and the Kaplan-Meier curve. Journal of the American Statistical Association 83, 414425.

DM Fergusson , LJ Horwood , JM Boden (2006). Structure of internalising symptoms in early adulthood. British Journal of Psychiatry 189, 540546.

LR Goldberg (1992). The development of markers for the big-five factor structure. Psychological Assessment 4, 2642.

P Gorwood (2004). Generalized anxiety disorder and major depressive disorder comorbidity: an example of genetic pleiotropy? European Psychiatry 19, 2733.

JM Haro , S Arbabzadeh-Bouchez , TS Brugha , G di Girolamo , ME Guyer , R Jin , JP Lepine , F Mazzi , B Reneses , G Vilagut Saiz , NA Sampson , RC Kessler (2006). Concordance of the Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) with standardized clinical assessments in the WHO World Mental Health Surveys. International Journal of Methods in Psychiatric Research 15, 167180.

JM Hettema , MC Neale , JM Myers , CA Prescott , KS Kendler (2006). A population-based twin study of the relationship between neuroticism and internalizing disorders. American Journal of Psychiatry 163, 857864.

KS Kendler , CG Davis , RC Kessler (1997). The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: a family history study. British Journal of Psychiatry 170, 541548.

KS Kendler , MC Neale , RC Kessler , AC Heath , LJ Eaves (1992). Generalized anxiety disorder in women. A population-based twin study. Archives of General Psychiatry 49, 267272.

RC Kessler (1977). Rethinking the 16-fold table problem. Social Science Research 6, 84107.

RC Kessler (2000). The epidemiology of pure and comorbid generalized anxiety disorder: a review and evaluation of recent research. Acta Psychiatrica Scandinavica Supplement 713.

RC Kessler , WT Chiu , O Demler , KR Merikangas , EE Walters (2005). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 617627.

RC Kessler , CG Davis , KS Kendler (1997). Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey. Psychological Medicine 27, 11011119.

RC Kessler , KA McGonagle , S Zhao , CB Nelson , M Hughes , S Eshleman , HU Wittchen , KS Kendler (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Archives of General Psychiatry 51, 819.

RC Kessler , TB Ustun (2004). The World Mental Health (WMH) Survey Initiative Version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). International Journal of Methods in Psychiatric Research 13, 93121.

RC Kessler , H-U Wittchen , JM Abelson , KA McGonagle , N Schwarz , KS Kendler , B Knäuper , S Zhao (1998). Methodological studies of the Composite International Diagnostic Interview (CIDI) in the US National Comorbidity Survey. International Journal of Methods in Psychiatric Research 7, 3355.

RF Krueger (1999). The structure of common mental disorders. Archives of General Psychiatry 56, 921926.

RF Krueger , A Caspi , TE Moffitt , PA Silva (1998). The structure and stability of common mental disorders (DSM-III-R): a longitudinal-epidemiological study. Journal of Abnormal Psychology 107, 216227.

KD Mickelson , RC Kessler , PR Shaver (1997). Adult attachment in a nationally representative sample. Journal of Personality and Social Psychology 73, 10921106.

R Noyes Jr. (2001). Comorbidity in generalized anxiety disorder. Psychiatric Clinics of North America 24, 4155.

RM Post , SR Weiss (1998). Sensitization and kindling phenomena in mood, anxiety, and obsessive-compulsive disorders: the role of serotonergic mechanisms in illness progression. Biological Psychiatry 44, 193206.

LN Robins , J Wing , HU Wittchen , JE Helzer , TF Babor , J Burke , A Farmer , A Jablenski , R Pickens , DA Regier , A Farmer , A Jablenski , R Pickens , DA Regier , N Sartorious , LH Towle (1988). The Composite International Diagnostic Interview. An epidemiologic instrument suitable for use in conjunction with different diagnostic systems and in different cultures. Archives of General Psychiatry 45, 10691077.

PR Rosenbaum , DB Rubin (1983). The central role of the propensity score in observational studies for causal effects. Biometrika 70, 4155.

RL Spitzer , JB Williams , M Gibbon , MB First (1992). The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Archives of General Psychiatry 49, 624629.

WA Vollebergh , J Iedema , RV Bijl , R de Graaf , F Smit , J Ormel (2001). The structure and stability of common mental disorders: the NEMESIS study. Archives of General Psychiatry 58, 597603.

D Watson (2005). Rethinking the mood and anxiety disorders: a quantitative hierarchical model for DSM-V. Journal of Abnormal Psychology 114, 522536.

KA Yonkers , MG Warshaw , AO Massion , MB Keller (1996). Phenomenology and course of generalised anxiety disorder. British Journal of Psychiatry 168, 308313.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 8
Total number of PDF views: 88 *
Loading metrics...

Abstract views

Total abstract views: 362 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 28th June 2017. This data will be updated every 24 hours.