Increased metabolic risk in young people with emerging mood disorders and circadian rhythm disruption.

Background: Severe mental disorders are associated with increased risk of metabolic dysfunction. The objective of this study was to compare metabolic profiles across three proposed pathophysiological subtypes of common mood disorders (“hyperarousal-anxious depression”, “circadian-bipolar”, and “neurodevelopmental-psychosis”). Methods: 790 young people (aged 16 to 25; mean age 20.70 ± 4.91) were recruited from early intervention mental health services between 2004 and 2024 and assigned to three mood disorder subgroups (hyperarousal-anxious depression (n = 656), circadian-bipolar (n = 95), and neurodevelopmental-psychosis (n = 39)). We conducted cross-sectional assessments and between-group comparisons of metabolic and immune risk factors. Immune-metabolic markers included body mass index (BMI), fasting glucose (FG), fasting insulin (FI), Homeostasis Model Assessment-Insulin Resistance (HOMA2-IR), C-reactive protein (CRP), and blood lipids. Results: There were significant between-group differences in FG (F = 3.159, p = 0.043), FI (F = 3.488, p = 0.031), and HOMA2-IR (F = 3.907, p = 0.020). Post-hoc comparisons showed fasting insulin and HOMA2-IR were significantly higher in the circadian-bipolar group as compared to hyperarousal-anxious depression (p = 0.049 and p = 0.028, respectively). We then differentiated those with the hyperarousal-anxious subtype on the on the basis of low versus high BMI (< 25kg/m2 vs. > 25kg/m2 respectively). The circadian-bipolar group had higher fasting glucose, fasting insulin, HOMA2-IR, and HDL cholesterol than those with low BMI. Conclusions: Circadian disturbance may be driving increased rates of metabolic dysfunction among youth with emerging mood disorders, while increased BMI also remains a key determinant. Implications for assessment and early interventions are discussed.