Internalizing psychopathology and all-cause mortality: a comparison of transdiagnostic vs. diagnosis-based risk prediction

Abstract

Previous studies have documented the utility of a transdiagnostic internalizing factor in predicting important future outcomes (e.g., subsequent mental disorder diagnoses). To date, however, no study has investigated whether an internalizing factor predicts mortality risk. Also, while pre-vious studies of mortality risk have emphasized its associations with particular internalizing disorders, no study has assessed how the transdiagnostic internalizing factor vs. disorder-specific variance differently predict that risk. The primary aims of this study were to explore: a) whether the internalizing factor predicts mortality risk, b) whether particular internalizing psychopathologies uniquely predict mortality risk over and beyond the transdiagnostic internalizing factor, and c) whether there is a significant interaction of internalizing with self-reported health in the prediction of mortality risk. We utilized a large national sample of American adults from the Midlife in the United States (MIDUS), a longitudinal study that examined midlife development of individuals across multiple waves between 1995 and 2015. Data were analyzed for the 6,329 participants who completed the phone interview and self-administered questionnaire in MIDUS 1 (1995-1996) and were then followed up until October 31, 2015 or until death. To investigate the association between internalizing and mortality risk, we used the semi-parametric proportional hazards Cox model, where survival time was regressed on a latent internalizing factor. Overall findings indicate that a transdiagnostic internalizing factor significantly predicts mortality risk over a 20-year period (hazard ratio, HR=1.12, 95% CI: 1.05-1.16, p<0.01) and that internalizing outperforms disorder-specific variance (e.g., depression-specific variance) in the prediction of that risk. Further, there was a significant interaction between transdiagnostic internalizing and self-reported health, whereby internalizing psychopathology had a specific association with early death for individuals with excellent self-reported health condition (HR=1.50, 95% CI: 1.17-1.84, p<0.05). This highlights the clinical utility of using the transdiagnostic internalizing factor for prediction of an important future outcome, and supports the argument that internalizing psychopathology can be a meaningful liability to explore in public health practice.

Keywords: Internalizing factor; diagnosis-based prediction; generalized anx­iety disorder; major depressive disorder; mortality; neuroticism; panic disorder; transdiagnostic prediction.

Figure 1

Comparative predictive validity analysis. Arrows flowing from the latent internalizing factor to its indicators represent factor loadings, which were all statistically significant at p<0.001. The arrow leading from internalizing to survival time represents the hazard ratio of the Cox regression model, which was significant at p<0.01. Arrows leading from each of the residual variance to survival time represent the hazard ratios of each Cox regression model, which were all non‐significant. MDD – major depressive disorder, GAD – generalized anxiety disorder, PAN – panic disorder, NEURO – neuroticism, R = residual variance.