Testing a causal model of sleep and circadian rhythm disturbance and youth-onset mood disorders
Grantholders
Prof Ian Hickie
University of Sydney, Australia
Prof Jan Scott
Newcastle University, United Kingdom
Dr Kathleen Merikangas
National Institute of Mental Health, United States
Prof Naomi Wray
University of Queensland, Australia
Prof Sarah Medland
Queensland Institute of Medical Research, Australia
Prof Ronald Grunstein
Woolcock Institute of Medical Research
Prof Sharon Naismith
University of Sydney, Australia
Dr Jacob Crouse
University of Sydney, Australia
Prof Matt Trau
University of Queensland, Australia
Dr Sean Cain
Monash University, Australia
Mr Samuel Hockey
University of Sydney
Dr Frank Iorfino
University of Sydney, Australia
Project summary
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.