Psychological Medicine

Original Articles

Co-morbidity between major depressive disorder and anxiety disorders: shared etiology or direct causation?

A. R. Mathewa1, J. W. Pettita2 c1, P. M. Lewinsohna3, J. R. Seeleya3 and R. E. Robertsa4

a1 University of Houston, Houston, TX, USA

a2 Florida International University, Miami, FL, USA

a3 Oregon Research Institute, Eugene, OR, USA

a4 University of Texas Health Science Center, Houston, TX, USA


Background Major depressive disorder (MDD) and anxiety disorders (ANX) are debilitating and prevalent conditions that often co-occur in adolescence and young adulthood. The leading theoretical models of their co-morbidity include the direct causation model and the shared etiology model. The present study compared these etiological models of MDD–ANX co-morbidity in a large, prospective, non-clinical sample of adolescents tracked through age 30.

Method Logistic regression was used to examine cross-sectional associations between ANX and MDD at Time 1 (T1). In prospective analyses, Cox proportional hazards models were used to examine T1 predictors of subsequent disorder onset, including risk factors specific to each disorder or common to both disorders. Prospective predictive effect of a lifetime history of one disorder (e.g. MDD) on the subsequent onset of the second disorder (e.g. ANX) was then examined. This step was repeated while controlling for common risk factors.

Results The findings supported relatively distinct profiles of risk between MDD and ANX depending on order of development. Whereas the shared etiology model best explained co-morbid cases in which MDD preceded ANX, direct causation was supported for co-morbid cases in which ANX preceded MDD.

Conclusions Consistent with previous research, significant cross-sectional and prospective associations were found between MDD and ANX. The results of the present study suggest that different etiological models may characterize the co-morbidity between MDD and ANX based upon the temporal order of onset. Implications for classification and prevention efforts are discussed.

(Received May 16 2010)

(Revised February 27 2011)

(Accepted February 28 2011)

(Online publication March 25 2011)