Testing a causal model of sleep and circadian rhythm disturbance and youth- onset mood disorders

We hypothesise that sleep and circadian rhythm disturbance (SCRD) is a pathophysiological mechanism underpinning a significant subset of youth-onset mood disorders called “circadian depression”. To test this hypothesis, and to evaluate the effectiveness of SCRD-targeted interventions for youth with circadian depression, our five key goals are: - To explore in an early intervention youth cohort the dynamic, prospective relationships among mental health, SCRDs, biological/environmental factors (e.g., light sensitivity, light exposure), and treatment-associated changes over time. - To disentangle the genetic, environmental, and phenotypic links among SCRDs and youth-onset mood disorders in our longitudinal twin, family, and case-cohort studies. - To test in a multi-site randomised controlled trial, whether melatonin plus dCBT-I is a more effective early intervention for youth-onset mood disorders than placebo plus dCBT-I, and whether treatment-associated changes in SCRDs causally mediate changes in depressive symptoms. - To develop and evaluate novel, multiplex, blood-based biosensors to track SCRD biomarkers at in vivo state (“Circadian Chip”) and trait (“Red Blood Cell Signature Sensor”) timescales. - To integrate data with clinical and lived experience expertise in a computational model of youth-onset mood disorders, and to release an interactive dashboard so users can explore links among SCRDs and mental health and test novel hypotheses via computer simulation.