Obesity is the fifth leading cause of death globally and one of the leading causes of disability. While the general medical impacts of obesity, including cerebrovascular complications, are relatively well-recognized, the less obvious effects on brain health are often overlooked. Obesity is frequently linked with brain cortical thinning, subcortical atrophy, accelerated brain aging, cognitive impairments, and an increased risk of dementia, even in absence of additional cardiovascular risk factors. This is particularly concerning in people with severe mental illness (SMI), where the rates of obesity are high and the brain effects of obesity and psychiatric disorders may interact. Indeed, we and others have demonstrated that obesity adds to brain gray and white matter alterations in SMIs. Variations in extent of obesity contribute to variations in extent of brain alterations in people with bipolar disorders or schizophrenia. Importantly, obesity related brain changes explain part of the cognitive impairment already in people with first episode of psychosis. Moreover, baseline weight or weight gain predict future acceleration of brain aging and hippocampal atrophy across SMIs. These brain effects could explain why obesity in SMI is associated with worse psychiatric outcomes, including greater psychiatric morbidity, chronicity, disability, functional decline, and worse responses to psychiatric medications. Monitoring weight and body composition thus becomes relevant for managing psychiatric, cognitive and brain health. Future research should investigate if prevention or treatment of obesity, i.e. with GLP1 agonists, could prevent or improve neurostructural changes and related psychiatric outcomes, including cognitive impairment.

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