PROJECT SUMMARY/ABSTRACT The aim of the proposed K01 Mentored Research Scientist Development Award is to provide the candidate with advanced expertise in developmental affective neuroscience and sleep research. Adolescence is a period of heightened vulnerability to bipolar disorder (BD), and parental history of BD is a robust risk factor. Impairments in reward processing and cognitive control are hypothesized to represent core mechanisms of BD, as well as psychiatric conditions that often precede or co-occur with BD. In adolescence, maturation of functional connections among neural circuitry supporting reward-control processes parallel rising BD incidence rates. Neurobehavioral impairments in these domains are observed even in psychiatrically healthy offspring of bipolar parents, perhaps reflecting vulnerabilities to subsequent psychopathology. To inform more potent preventative treatments for BD, it is important to characterize modifiable factors that engage these transdiagnostic neurobehavioral targets hypothesized to underlie risk for BD and related forms of psychopathology, particularly in high-risk samples. Sleep is disturbed across most forms of psychopathology. Sleep patterns become increasingly variable in adolescence, and sleep is an established contributor to brain plasticity and function. Increased sleep variability could confer more adverse effects in offspring of bipolar parents, for whom neural circuitry may already be compromised. However, it is possible that stabilizing sleep may protect vulnerable neural circuitry in offspring of bipolar parents. The proposed research aims to test a model in which sleep variability exacerbates pre-existing neurobehavioral vulnerabilities (reward processing, cognitive control) in adolescent offspring of bipolar parents relative to healthy adolescents. Adolescents aged 14-18yr will be recruited: 30 low-risk healthy offspring of healthy parents (LR) and a unique sample of 30 high- risk offspring of bipolar parents (HR), further enriched for risk via the presence of a range of non-BD psychopathology. All participants will complete well-validated daily sleep measures followed by fMRI and behavioral measures of reward processing and cognitive control. For fMRI, task-related activity and connectivity among interconnected neural circuits supporting reward processing (ventral frontostriatal) and cognitive control (dorsal prefrontal) will be assessed. The primary aims assess sleep variability as a predictor of subsequent neurobehavioral deficits in reward processing (Aim 1) and cognitive control (Aim 2) in HR and LR. It is predicted that relationships between sleep and neurobehavioral function will be moderated by group status, such that sleep variability will be more strongly related to impaired neurobehavioral function in HR relative to LR. The exploratory aim will test the extent to which stabilizing sleep variability (via a brief behavioral manipulation) modulates these neurobehavioral measures in a s...