Evaluating the distinct effects of body mass index at childhood and adulthood on adult major psychiatric disorders

Children with high body mass index (BMI) are at heightened risk of developing health issues in adulthood, yet the causality between childhood BMI and adult psychiatric disorders remains unclear. Using a life course Mendelian randomization (MR) framework, we investigated the causal effects of childhood and adulthood BMI on adult psychiatric disorders, including Alzheimer's disease, anxiety, major depressive disorder, obsessive-compulsive disorder (OCD), and schizophrenia, using data from the Psychiatric Genomics Consortium and FinnGen study. Childhood BMI was significantly associated with an increased risk of schizophrenia, while adulthood BMI was associated with a decreased risk of OCD and schizophrenia. Multivariable MR analyses indicated a direct causal effect of childhood BMI on schizophrenia, independent of adulthood BMI and lifestyle factors. No evidence of causal associations was found between childhood BMI and other psychiatric outcomes. The sensitivity analyses yielded broadly consistent findings. These findings highlight the critical importance of early-life interventions to mitigate the long-term consequences of childhood adiposity.