The Causal Role of Adiposity in Mental Illness: A Systematic Review and Meta-Analysis of Mendelian Randomization...

This study aimed to examine the causal effect of adiposity on mental illnesses by summarizing and assessing evidence from Mendelian randomization (MR) studies.

Searches were conducted on Embase, Medline, and Web of Science from database inception to September 22nd, 2025. Studies using MR study designs that estimated adiposity measures including body mass index, abdominal adiposity, peripheral adiposity, or body composition in relation to mental illnesses were included. Outcomes were the presence or severity of depression, anxiety, eating disorders, bipolar disorder, obsessive compulsive disorder, post-traumatic stress disorder, schizophrenia, and related psychotic disorders. Study quality was assessed with a scoring system reflecting MR study guidelines. Data were pooled in meta-analyses using random-effects models. Subgroup analyses were conducted by sex.

Fifty-seven studies with 215 MR estimates were included in the systematic review, and 23 studies with 44 MR estimates were included in meta-analyses. Pooled estimates suggested that general adiposity was causally associated with depression (OR: 1.09, 95% CI, 1.02-1.15, p < 0.001; I² = 94%), but the effect size was modest and there was high heterogeneity. Subgroup differences by sex in the causal relationship were not observed (p = 0.318). There was suggestive evidence for causal associations of adiposity with schizophrenia and OCD; however, these analyses were characterized by high imprecision and heterogeneity. The evidence for other mental illnesses remains unclear.

General adiposity appears to be causally associated with depression, suggesting psychological benefits of weight management. Evidence for causal associations between adiposity and other mental illnesses remains suggestive or uncertain.