Immunometabolic Blood Biomarkers of Developmental Trajectories of Depressive Symptoms: Findings From the ALSPAC Birth Cohort

Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiologic mechanism, heterogeneity and origin of common cardiometabolic comorbidities for depression. Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n=7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%). We examined associations of these trajectories with: i) anthropometric, cardiometabolic and psychiatric phenotypes using multivariable regression (n=1709-3410); ii) 67 blood immunological proteins and 57 metabolomic features using empirical Bayes moderated linear models (n=2059 and n=2240 respectively); and iii) 28 blood cell counts and biochemical measures using multivariable regression (n=2256). Relative to the low-stable group, risk of depression and anxiety in adulthood was higher for all other groups, especially in the adolescent-persistent (OR _depression =22.80, 95% CI 15.25-34.37; OR _GAD =19.32, 95% CI 12.86-29.22) and adulthood-onset (OR _depression =7.68, 95% CI 5.31-11.17; OR _GAD =5.39, 95% CI 3.65-7.94) groups. The three depression-related trajectories vary in their immunometabolic profile, with evidence of little or no alterations in the adolescent-limited group. The adulthood-onset group shows widespread classical immunometabolic changes (e.g., increased immune cell counts and insulin resistance), while the adolescent-persistent group is characterised by higher BMI both in childhood and adulthood with few other immunometabolic changes. These findings point to distinct mechanisms and intervention opportunities for adverse cardiometabolic profile in different groups of young people with depression.