Childhood Immuno-metabolic Markers and Risk of Depression and Psychosis in Adulthood: A Prospective Birth Cohort Study

Background Metabolic and inflammatory disorders commonly co-occur with depression and psychosis, with emerging evidence implicating immuno-metabolic dysfunction in their aetiology. Previous studies have reported metabolic dysfunction and inflammation in adults with depression and psychosis. However, longitudinal studies testing the direction of association, and the effects of different dimensions of early-life immuno-metabolic dysfunction on adult psychopathology, are limited. Methods Using data from 3875 birth cohort participants we examined longitudinal associations of three metabolic hormones (leptin, adiponectin, insulin) at age 9 with risks for depression- and psychosis-spectrum outcomes at age 24. In addition, using nine immuno-metabolic biomarkers, we constructed an exploratory bifactor model showing a general immuno-metabolic factor and three specific factors (adiposity, inflammation, and insulin resistance), which were also used as exposures. Results Childhood leptin was associated with adult depressive episode (adjusted odds ratio (aOR)=1.28; 95% CI, 1.00-1.64) and negative symptoms (aOR=1.12; 95% CI, 1.05-1.20). The general immuno-metabolic factor was associated with depressive symptoms (aOR=1.05; 95% CI, 1.01-1.08) and psychotic experiences (aOR=1.20; 95% CI, 1.01-1.42). The adiposity factor was associated with negative symptoms (aOR=1.07; 95% CI 1.02-1.12). All associations tended to be stronger in women, though 95% credible intervals overlapped with that for men. In women, the inflammatory factor was associated with depressive episode (aOR=1.23; 95% CI, 1.01-1.47) and atypical depressive symptoms (aOR=1.10; 95% CI, 1.02-1.19). Conclusions While general immuno-metabolic dysfunction in childhood may contribute to risks for both psychotic and depressive symptoms in adulthood, childhood adiposity and inflammation are linked to affective (depressive, atypical, and negative) symptoms.