Adiposity and the first-onset of diagnosed mental illnesses: a population-based cohort study of 10 million UK adults.

Severe obesity was associated with higher risks for multiple mental illnesses compared to healthy BMI.

• Compared to healthy BMI (18.5–25.0 kg/m²), severe obesity (≥40 kg/m²) was associated with higher risks for depression (HR 1.32; 95% CI 1.31–1.33), anxiety (1.12; 1.10–1.13), bulimia nervosa (1.38; 1.20–1.58), other unspecified eating disorders (2.04; 1.91–2.17), bipolar disorder (1.44; 1.36–1.54), schizophrenia (2.02; 1.91–2.15), and other psychoses (1.40; 1.28–1.53).
• Severe obesity was associated with a lower risk for anorexia nervosa (HR 0.45; 95% CI 0.42–0.49).
• Study population included 10,465,562 adults with mean BMI 26.8 kg/m² (SD 5.5), drawn from the UK Clinical Practice Research Datalink (2000–2022).
• Mental illnesses were ascertained via clinical diagnoses, referrals to mental health services, or psychotropic prescriptions.

Underweight was associated with increased risks of several mental illnesses including very high risks for eating disorders.

• Individuals with underweight (<18.5 kg/m²) had increased risks of depression (HR 1.28; 95% CI 1.27–1.29), anxiety (1.26; 1.24–1.27), anorexia nervosa (3.88; 3.77–4.01), bulimia nervosa (1.52; 1.37–1.68), other unspecified eating disorders (4.50; 4.33–4.67), schizophrenia (1.46; 1.35–1.56), and other psychoses (1.22; 1.10–1.35).
• There was no association between underweight and bipolar disorder.
• Underweight showed notably high hazard ratios for eating disorders, with other unspecified eating disorders having an HR of 4.50 and anorexia nervosa an HR of 3.88 compared to healthy BMI.

Associations between BMI and mental illness were stronger in women, younger adults, and Asian populations.

• Subgroup analyses identified women, younger adults, and Asian populations as groups with stronger associations between adiposity extremes and mental illness risk.
• These effect modifications were observed across both the underweight and severe obesity categories.
• The study used a population of 10,465,562 UK adults, allowing detection of subgroup effects across demographic groups.

Cardiometabolic diseases did not mediate the associations between BMI and mental illness, but certain biomarkers demonstrated partial mediation.

• Mediation analyses assessed the mediating role of cardiometabolic disorders and biomarkers including LDL, triglycerides, and HbA1c.
• Cardiometabolic diseases did not mediate the associations between BMI extremes and mental illness.
• LDL, triglycerides, and HbA1c demonstrated partial mediation with indirect effects ranging from 0.2% to 15%.
• The partial mediation by biomarkers suggests metabolic pathways play a limited but present role in linking adiposity to mental illness.

Both high and low BMI represent risk factors for serious mental illnesses including schizophrenia and bipolar disorder.

• Severe obesity was associated with schizophrenia (HR 2.02; 95% CI 1.91–2.15) and bipolar disorder (HR 1.44; 95% CI 1.36–1.54).
• Underweight was associated with schizophrenia (HR 1.46; 95% CI 1.35–1.56) and other psychoses (HR 1.22; 95% CI 1.10–1.35), but not with bipolar disorder.
• Associations were identified in a cohort of over 10 million UK adults followed from 2000 to 2022 using Cox proportional hazard models and restricted cubic splines.
• These findings address the previously unclear question of whether both high and low BMI are risk factors for serious mental illnesses.