What is the clinical evidence from this study?

Study design: Observational. Population: Schizophrenia, clinical high-risk states for psychosis, recent-onset depression (n=2063). Intervention: BMIgap tool. Primary outcome: BMIgap (BMI predicted - BMI measured) and future weight gain.

October 20, 2025Nature Mental Health1 citationsOpen Access

The BMIgap tool to quantify transdiagnostic brain signatures of current and future weight

AKAdyasha KhuntiaMax Planck Institute of Psychiatry DPDavid PopovicMax Planck Institute of Psychiatry ESElif SarisikMax Planck Institute of Psychiatry

Key Result

A brain-derived BMIgap model showed increased values in schizophrenia (1.05 kg/m2) and clinical high-risk states (0.51 kg/m2), and higher BMIgap predicted future weight gain at 2-year follow-up.

Study Design

Type

Observational (n=2,063)

Structured PICO

Does the brain-derived BMIgap measure predict future weight gain and stratify metabolic risk in individuals with psychiatric disorders?

Population

Healthy individuals (n=1,504), individuals with schizophrenia (n=146), clinical high-risk states for psychosis (n=213) and recent-onset depression (ROD, n=200).

Intervention

BMIgap tool (BMI predicted − BMI measured) derived from brain scans

Outcome

BMIgap differences across clinical groups and prediction of weight gain at 1-year and 2-year follow-upssurrogate

BMIgap, a brain-derived measure of BMI deviation, can identify distinct neurobiological patterns in psychiatric disorders and predict future weight gain, offering a potential tool for metabolic risk stratification.

Abstract

Abstract Understanding the neurobiological underpinnings of weight gain could reduce excess mortality and improve long-term trajectories of psychiatric disorders. Using brain scans from healthy individuals ( n = 1,504), we trained a model to predict body mass index (BMI) and applied it to individuals with schizophrenia ( n = 146), clinical high-risk states for psychosis ( n = 213) and recent-onset depression (ROD, n = 200). We computed BMIgap (BMI predicted − BMI measured ), interrogated its brain-level overlaps with schizophrenia and explored whether BMIgap predicted weight gain at the 1-year and 2-year follow-ups. Schizophrenia (BMIgap = 1.05 kg m − 2 ) and clinical high-risk individuals (BMIgap = 0.51 kg m − 2 ) showed increased BMIgap and individuals with ROD (BMIgap = −0.82 kg m − 2 ) showed decreased BMIgap. Shared brain patterns of BMI and schizophrenia were linked to illness duration, disease onset and hospitalization frequency. Higher BMIgap predicted future weight gain, particularly in younger individuals with ROD, and at 2-year follow-up. Here we show that BMIgap can serve as a potential brain-derived measure to stratify at-risk individuals and deliver tailored interventions for better metabolic risk control.

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