Objectives Lifestyle interventions targeting weight loss currently show limited benefits for individuals with major mood disorders. Sleep-wake disturbances are prevalent in youth with mood disorders and linked to metabolic dysfunction. This study evaluates whether sleep-wake disturbance is a driver of metabolic dysfunction for individuals with major mood disorders, as compared to the existing theory that weight gain is the main contributor.

Design Longitudinal cohort study in 1712 individuals aged 21 to 30 years. Spearmans’ correlation coefficients between depressive symptoms, sleep-wake cycle disturbance, and metabolic variables at 21 and 30 years. Structural equation modelling explored: 1. A cross-lagged effects model of depressive symptoms, sleep-wake cycle disturbance and body mass index (BMI), and 2. A parallel mediation model comparing two indirect pathways between depressive symptoms at 21 years and HOMA2-IR (a measure of insulin-glucose homeostasis) at 30 years through sleep-wake disturbance and BMI.

Results We found a small correlation between depressive symptoms at 21 and HOMA2-IR at 30 (r=0.07, p<0.01). In the mediation model, the direct relationship between depressive symptoms at 21 and HOMA2-IR at 30 was no longer significant but there was a small total relationship (B=0.05, p<0.05) and a significant indirect pathway through sleep-wake disturbance (B=0.01, p<0.05). Although not a significant mediator, BMI at 30 was strongly related to HOMA2-IR (B=0.44, p <0.001).

Conclusion In this study, BMI was not a key mediator of the relationship between depressive symptoms and HOMA2-IR, while sleep-wake cycle disturbance appeared to play a small role. Work is needed in clinical populations with more robust measures of sleep-wake disturbance.

EMS COI: Associate Professor Elizabeth Scott is a Principal Research Fellow at the Brain and Mind Centre University of Sydney a Consultant Psychiatrist and Adjunct Clinical Professor at the School of Medicine University of Notre Dame. She previously served as the Discipline Leader for Adult Mental Health at Notre Dame until January 2025. In addition she is a member of Medibanks Medical and Mental Health Reference Groups. A/Prof Scott has also delivered educational seminars on the clinical management of depressive disorders receiving honoraria from pharmaceutical companies including Servier Janssen and Eli Lilly. Moreover she has contributed to a national advisory board for Pfizers antidepressant Pristiq and served as the National Coordinator for an antidepressant trial sponsored by Servier IBH COI: Professor Hickie is a Professor of Psychiatry and the Co-Director of Health and Policy Brain and Mind Centre University of Sydney. He has led major public health and health service development in Australia particularly focusing on early intervention for young people with depression suicidal thoughts and behaviours and complex mood disorders. He is active in the development through codesign implementation and continuous evaluation of new health information and personal monitoring technologies to drive highly-personalised and measurement-based care. He holds a 3.2% equity share in Innowell Pty Ltd that is focused on digital transformation of mental health services

JJC is supported by a NHMRC Emerging Leadership Fellowship (2008196); IBH is supported by a NHMRC Leadership L3 Fellowship (2016346); FI is funded by a NHMRC Emerging Leadership Fellowship (2018157). SM is supported by the Cottle Family Fellowship in Youth Mental Health. WC and MKC were supported by the Australian Government Research Training Program (RTP) Scholarship.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The University of Queensland Human Research Ethics Committee (mothers: B/555/SS/01/NHMRC - 30/11/2001, offspring: B/660/SS/01/NHMRC - 20/12/2001) and The Mater Human Research Ethics Committee (mothers: 505A - 29/6/2002, offspring: 506A - 15/07/2002).

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