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

Abstract

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.

La relation temporelle entre l’anxiété et la dépression dans le contexte de la transition primaire-secondaire

“…En présence d'une concomitance, plusieurs études démontrent que l'anxiété précède temporellement la dépression (Bittner et al, 2004 ;Mathew, Pettit, Lewinsohn, Seeley et Roberts, 2011 ;Zahn-Waxler, Klimes-Dougan et Slattery, 2000). La dépression primaire à l'anxiété semble plus rare, bien qu'elle soit parfois observée (Costello, Mustillo, Erkanli, Keeler et Angold 2003 ;Gallerani, Garber et Martin, 2010).…”

Early life course determinants of psychopathology

“…Recent prospective studies suggest that anxiety and depression are predicted by unique risk factors (71,73,(77)(78)(79)(80). Regarding comorbidity, some of these studies suggest that cooccurrence is more closely related to anxiety than depression, as anxiety and co-occurrence are predicted by the same risk factors, while depression is predicted by unique risk factors (78,79).…”

“…Regarding comorbidity, some of these studies suggest that cooccurrence is more closely related to anxiety than depression, as anxiety and co-occurrence are predicted by the same risk factors, while depression is predicted by unique risk factors (78,79). Further, primary anxiety remained predictive of later MDD after adjustment for common risk factors, while the reverse relationship was not found (80), suggesting anxiety is causally related to subsequent MDD development. However, there is also evidence that GAD+MDD is predicted by risk factors unrelated to either GAD or MDD (77), and that GAD+MDD when specified by the primary disorder is not associated with risk factors which differentially predict GAD and MDD (71).…”

“…MDD precedes GAD as often as GAD precedes MDD (74) and baseline MDD is strongly predictive of subsequent GAD (71), reducing confidence in the prodromal explanation and revealing the importance of specifying cooccurrence by the primary disorder. Lastly, longitudinal SEM studies find superior fit when the variance of anxiety and depression is accounted for by a general internalising component with additional disorder-specific components (75, 76).Recent prospective studies suggest that anxiety and depression are predicted by unique risk factors (71,73,(77)(78)(79)(80). Regarding comorbidity, some of these studies suggest that cooccurrence is more closely related to anxiety than depression, as anxiety and co-occurrence are predicted by the same risk factors, while depression is predicted by unique risk factors (78,79).…”

Treatment Moderation and Secondary Outcomes: Results from a Randomized Clinical Trial

“…This understanding is also important because it can inform classification efforts with respect to psychopathology. Empirically, evaluation of mediators could set the stage for future investigations into the reasons why anxiety is often comorbid with depressive symptoms and externalizing problem behaviors (e.g., Mathew, Pettit, Lewinsohn, Seeley, & Roberts, 2011). Clinically, evaluation of mediators could yield knowledge that may inform the development of more efficient and cost effective treatments to reduce not only anxiety but also depressive and externalizing problems.…”