Integrated Reward-Circadian Rhythm Model of First Onset of Bipolar Spectrum Disorders in Adolescence Supplement

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Project Summary/Abstract Adolescence is an “age of risk” for the emergence of first onset of bipolar spectrum disorders (BSD). Despite their prevalence and public health significance, major unanswered questions exist regarding the mechanisms involved in vulnerability to BSDs. BSDs are associated with hypersensitivity to reward and elevated reward- related brain function. However, research has not yet tested whether chronically high reward responsivity (RR) or increases in RR development during adolescence, beyond baseline RR, predicts first onset of BSD. A separate literature documents circadian rhythm disruption in BSDs, and social rhythm disruption (SRD) can trigger BSD episodes. Yet, research has not tested whether baseline circadian dysregulation, chronic social and circadian rhythm disruptions, or increases in these rhythm disruptions during adolescence predict onset of BSD. Further, circadian and reward approaches to BSDs mostly have proceeded in parallel. However, we and others have proposed integrated reward-circadian models of BSDs based on evidence the two systems influence each other and interact to affect mood functioning. When dysregulated, reward and circadian system signaling may combine to form a positive feedback loop, whereby dysregulation in one system exacerbates dysregulation in the other. This proposal is the first systematic test of a novel, integrated reward-circadian model for first onset of BSD. We will use an innovative biobehavioral high-risk design to examine bidirectional relationships between multiple indices and domains (monetary, social) of RR and multiple indices of social and circadian rhythms and their joint prediction of first onset of BSD and increases in bipolar symptoms. Three hundred twenty 14-16 year old participants (Ps) will complete a prospective 3-year longitudinal study. Ps with no prior BSD will be selected along the entire dimension of self-reported RR, with oversampling at the high tail of the dimension in order to increase the likelihood of BSD onsets. At Times 1-6, every 6 months, Ps will complete assessments of reward-relevant and SRD life events and self-report and diagnostic assessments of bipolar symptoms and episodes. Yearly, at Times 1, 3, and 5, Ps also will complete self-report measures of circadian chronotype (morningness-eveningness) and social rhythm regularity, a salivary dim light melatonin onset (DLMO) procedure to assess circadian phase, self-report, behavioral, and neural (fMRI) assessments of monetary and social RR, and a 7-day EMA period. During each EMA period, Ps will complete continuous measures of sleep/wake and activity (actigraphy) and 3 within-day (morning, afternoon, evening) measures of life events coded for reward-relevance and SRD, monetary and social reward responsivity, positive and negative affect, and hypo/manic and depressive symptoms. The fMRI scan and DLMO procedure will occur on the day before the start of each EMA period, excluding weekends. This proposal is an innovative integration of research on reward and circadian signaling in understanding first onset of BSD in adolescence. It has the potential to facilitate reward and social/circadian rhythm interventions to treat, and ideally prevent, BSD.