Uncovering relationships between 24-h rest-activity patterns and immune-metabolic dysfunction in young people with...

Individuals with mood disorders are at increased risk of premature mortality, notably from premature cardiovascular disease. Circadian (and linked 24 h rest-activity) disturbances are highly prevalent among this population and have also been linked to immune-metabolic dysfunction. Currently there is limited understanding of the extent to which these pathophysiological processes co-occur across the various clinical stages of major mood disorders.

225 young people (67 % female; aged 23.65 ± 5.73 years) recruited from early intervention mental health services were assigned clinically to either Stage 1a or 1b (subthreshold disorders) or Stage 2+ (full threshold disorder) of illness according to the transdiagnostic staging model. We explored relationships between immune-metabolic risk factors (BMI, fasting glucose and insulin, insulin resistance, and CRP) and rest-activity parameters from actigraphy (24 h ambulatory motor activity monitoring) using pairwise correlations, multiple linear regression interaction effects and subgroup analyses.

For all participants, higher intradaily variability (greater rest-activity fragmentation) was associated with higher BMI (r = 0.187, p = 0.043), fasting insulin (r = 0.180, p = 0.031), HOMA2-IR (r = 0.187, p = 0.043), and CRP (r = 0.178, p = 0.032) across all stages of illness. Lower relative amplitude of rest-activity patterns indicating dampened circadian rhythmicity, was associated with higher BMI (β = -33.149, p = 0.013) and CRP (β = -22.042, p = 0.053), only for those in stage 2+ of illness. It was also associated with fasting insulin during stage 1b (β = -10.299, p = 0.044) and stage 2 (β = -10.411, p = 0.037), and with HOMA2-IR at stage 1b (β = -1.133, p = 0.040). Finally, increased moderate-to-vigorous physical activity (MVPA) was associated with lower BMI only for those at Stage 2+ (β = -0.056, p = 0.001).

Objective measures of blunted and fragmented 24 h rest-activity (circadian) rhythms were associated with adverse immune-metabolic outcomes. Stabilization and amplitude-boosting of rest-activity rhythms may be particularly valuable targets for indicated prevention and early intervention of major mood disorders.