Research Domain Criteria (RDoC) Mechanisms of Transdiagnostic Polygenic Risk for Trajectories of Depression: From Early Adolescence to Adulthood

There is substantial heterogeneity in the development of depression from adolescence into adulthood. Yet, little is known about the risk factors underlying its various patterns of development. For instance, despite the discovery of genetic variants for depression, these discoveries have not accounted for the high degree of genetic covariation between multiple disorders, nor have they been applied to disambiguate its heterogeneous developmental presentations. This study examined the association between a transdiagnostic polygenic score for psychopathology (p-factor PGS) and depression trajectories, spanning early adolescence into adulthood, in the National Longitudinal Study of Adolescent to Adult Health (N = 7,088). We examined whether subconstructs of the Research Domain Criteria's (RDoC) negative valence (i.e., negative emotionality), positive valence (i.e., novelty seeking), and cognitive systems (i.e., picture vocabulary) could explain how the p-factor PGS eventuates into the various pathways of depression. Four trajectories were identified: low depression (78.9%), low increasing (7.3%), high declining (8.2%), and early adult peaked (5.7%). The p-factor PGS was significantly higher in all depressive trajectories relative to the low-depression trajectory but was predictive of only the trajectory that showed increasing depression over time: low increasing. A specific indirect path emerged by which the association of p-factor PGS on early adult peaked and high-declining depression operated through the effects of negative emotionality but not picture vocabulary or novelty seeking. Findings reinforce the crucial role of development in genetically informed RDoC models of depression, because there appear to be distinct correlates and risk factors that underlie the various developmental pathways of depression. General Scientific Summary There are individual differences in how depression symptoms progress over time, but little is known about the risk factors that underlie these developmental patterns. This study identifies distinct correlates and risk factors that underlie the various developmental pathways of depression. We found that transdiagnostic polygenic risks for psychopathology are predictive of worsening patterns of adolescent to adult depression and indirectly associated with the less severe patterns of depression via negative emotionality.