Research Domain Criteria (RDoC) mechanisms of transdiagnostic polygenic risk for trajectories of depression: From early adolescence to adulthood.

Abstract

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 ϭ 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.

The need to grow: Developmental considerations and challenges for modern psychiatric taxonomies.

“…But reliance on single dimensions in isolation (i.e., without simultaneous modeling of empirical covariation, such as in HiTOP) or rationally derived models that do not map onto manifest covariation patterns will lead us astray in the search for etiologic underpinnings. Li and colleagues (2022) highlight one such way these structural models can inform and accelerate investigations of etiologic risk factor by examining a polygenic risk factor for the p- factor of psychopathology, which also encompasses the highest and broadest level of the HiTOP structure. We could take this a step further and shed some light on what Li et al describe as “disorder-specific pathways” for depression, by turning to a common finding in p- factor structural models wherein depression actually loads directly on the p -factor, indicating no to little disorder-specific variance, and is also highly overlapping with trait neuroticism at the phenotypic and genetic levels (Tackett et al, 2013).…”

“…The empirical articles in this special section highlight key strengths of the developmental psychology research tradition, including the use of multiple informants (e.g., Liu et al, 2022), longitudinal designs (e.g., Li et al, 2022), and multiple-measure assessments of key constructs. Although we appreciate that not every biobehavioral study of psychopathology can afford to implement each of these strategies, the manifestation of psychopathology over the life span shows remarkable diagnostic heterogeneity and transitions among the spectra (internalizing, externalizing, and thought problems; Caspi et al, 2020).…”

“…We examine this agenda from the perspective of another modern approach to psychiatric classification: the Hierarchical Taxonomy of Psychopathology (HiTOP; Kotov et al, 2017). Building on four of the contributions to this special section (Damme et al, 2022; Li et al, 2022; Liu et al, 2022; Petersen & LeBeau, 2022), we highlight three areas for advancing developmental integration within broadband psychiatric frameworks: (a) the importance of structural models of personality and psychopathology, (b) the value of improving measurement and assessment, and (c) the opportunities offered to such frameworks by stronger integration of developmental context. We articulate ways in which the HiTOP model advances our understanding of mental health and its development beyond the RDoC approach, as well as areas in which developmental integration is lacking in both HiTOP and RDoC frameworks.…”

Integrating development into the Research Domain Criteria (RDoC) framework: Introduction to the special section.

“…Consistent with this, they show that, although higher levels of irritability in preschool (an index of frustrative nonreward, a negative valence domain construct), measured using a parent-report questionnaire, are a diffuse predictor of varied behavior problems in preadolescence-an example of multifinalityhigher levels of irritability in early childhood are specific to preadolescent externalizing problems, as well as reduced volume in some brain regions, as measured by MRI. Li et al (2022) embrace the emphasis of the RDoC framework on transdiagnostic processes in their examination of associations between a polygenic score (PGS) for general psychopathology (the p factor) and multiple RDoC dimensions, including negative emotionality (an index that spans acute threat, potential threat, sustained threat, loss, and frustrative nonreward, the negative valence domain constructs), novelty seeking (an index of reward responsiveness, a positive valence domain construct), and picture vocabulary (an index of language, a cognitive domain construct), measured using selfreport questionnaires and performance on a neurocognitive test. They find that the transdiagnostic PGS predicted depression trajectories during the transition from adolescence into early adulthood, as well as suggestive evidence of a specific indirect association for negative emotionality (but not novelty seeking or picture vocabulary).…”

“…Li et al (2022) embrace the emphasis of the RDoC framework on transdiagnostic processes in their examination of associations between a polygenic score (PGS) for general psychopathology (the p factor) and multiple RDoC dimensions, including negative emotionality (an index that spans acute threat, potential threat, sustained threat, loss, and frustrative nonreward, the negative valence domain constructs), novelty seeking (an index of reward responsiveness, a positive valence domain construct), and picture vocabulary (an index of language, a cognitive domain construct), measured using self-report questionnaires and performance on a neurocognitive test. They find that the transdiagnostic PGS predicted depression trajectories during the transition from adolescence into early adulthood, as well as suggestive evidence of a specific indirect association for negative emotionality (but not novelty seeking or picture vocabulary).…”