Early risk factors for metabolic dysfunction in young people with major mood disorders: Longitudinal path analysis of a prospective birth cohort using structural equation modelling.

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.