Biotyping Mood Health in Late Adolescence: Neurocognitive Dimensions and Stress Pathways

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Project Summary Adolescence is a developmental period marked by interconnected changes in cognitive and neurobiological functioning, including reorganization of large-scale functional networks and improved ability to regulate attention and pursue rewards. Adolescence is also a period characterized by heightened stress and increased symptoms of mood disorders (MD), which are in turn associated with neurocognitive abnormalities in the same brain networks and cognitive domains that are highly plastic in adolescence. These developmental convergences suggest a model in which abnormalities in key neurocognitive dimensions predispose teens to MD, possibly because neurocognitive impairment impedes healthy stress coping behavior. However, shared risk factors and similarities in early-stage symptomatology of various MD have made it challenging to determine the specific pathways by which neurocognitive abnormalities contribute to MD. The proposed study will address these challenges with a multi-modal, longitudinal evaluation of risk “biotypes”, stress responses, and MD symptoms in adolescence. We will recruit a sample of n=144 adolescents ages 14-19 (n=96 at high familial risk of MD) to participate in a 24-month study consisting of neuroimaging, cognitive testing, and symptom assessment (at baseline and 12 months), and mobile-app/telephone follow-up evaluations (once per 6 months) of stress events/responses and symptoms. We will apply latent variable analysis to behavioral and neuroimaging measures to evaluate individual differences in key neurocognitive dimensions related to: (1) cognitive regulation (CR), and (2) reward sensitivity (RS). Multilevel models will test the effects of CR and RS on future mood symptoms as mediated by stress-reactive behaviors. We aim to first use biotypes defined by abnormalities in these neurocognitive dimensions to predict stress-reactive behavior and mood symptoms over a two-year follow- up (Aim 1), and to second, provide a more precise understanding of neurocognitive subdimensions – focusing on RS subdimensions - that best carve the mood symptom space (Aim 2). In addition, in order to explore temporal characteristics of biotypes, we will test the stability of RS over time (Exploratory Aim 1) and to explore moderators of biotype expression, we will test the effects of biological sex and age (Exploratory Aim 2). Ultimately, this work may be a crucial step towards the translational goal of using neurocognitive biotypes to differentially diagnose and predict MD.