Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals

Abstract

Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive.Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia.

Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area

“…11 Obesity impacts physical health and mortality, and it may also affect mental health and brain structure. 12 There is some evidence that obesity may worsen schizophrenia symptoms by disrupting white matter and reducing brain structural connectivity. 11 However, underweight status is also associated with health risks, and a low body mass index (BMI) can also reflect self-neglect or physical frailty.…”

“…For instance, in patients with schizophrenia, olanzapine and clozapine are the most commonly used atypical antipsychotics that may increase the intake of food or lead to oxidative damage, causing obesity 11. Obesity impacts physical health and mortality, and it may also affect mental health and brain structure 12. There is some evidence that obesity may worsen schizophrenia symptoms by disrupting white matter and reducing brain structural connectivity 11…”

“… 11 Obesity impacts physical health and mortality, and it may also affect mental health and brain structure. 12 There is some evidence that obesity may worsen schizophrenia symptoms by disrupting white matter and reducing brain structural connectivity. 11 …”

Are the antidepressant effects of insulin-sensitizing medications related to improvements in metabolic markers?

“…It is well established that obesity is a risk factor for mood disorders and vice versa [50][51][52]. In addition, obesity is consistently associated with cognitive impairment [53] and neurostructural alterations [54][55][56][57]. There is some evidence suggesting that weight loss may improve brain structure [58] which could also positively impact cognitive functions [59] and/or psychiatric symptoms [60].…”

Impact of excessive abdominal obesity on brain microstructural abnormality in schizophrenia

“…McWhinney et al ( 2022) examined BMI and MRI-derived brain cortical and subcortical measures from 1260 individuals with SZ and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group; there were widespread associations between BMI and brain structure, and the regional statistical effects of obesity were most widespread in cortical GM thickness, with fewer correlates in subcortical GM volumes 21 . Although BMI has traditionally been used to classify obesity, a major limitation of BMI is that it is unable to differentiate between an elevated body fat and increased muscle mass 22 .…”