Cortical surface area as a stronger mediator of the waist-to-height ratio and cognitive impairment link in patients with first-episode schizophrenia compared to body mass index and waist-hip ratio.

Objective: The high metabolic risk and inherent brain structural changes in patients with schizophrenia are associated with cognitive impairment; however, the underlying mechanism remains unclear. This study investigated whether cortical surface area (CSA) and cortical thickness (CT) mediate obesity-related cognitive impairment in patients with first-episode schizophrenia (FEPS).

Methods: We included 160 patients with FEPS and 150 healthy controls (HCs). Cognitive function and psychiatric symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) and the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). The CSA and CT of 34 grey matter regions in each hemisphere were measured using 3.0-T magnetic resonance imaging. Obesity metrics included waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body mass index (BMI).

Results: HCs had significantly higher CSA and CT in several brain regions than FEPS after adjusting for covariates (p < 0.05). WHR significantly correlated with Verbal Learning, Working Memory, and MCCB composite scores, while WHtR was linked to Social Cognition and MCCB composite scores (p < 0.05). Bilateral CSA mediated the associations between WHR, WHtR, and MCCB scores (p < 0.05), with stronger mediation observed for WHtR. Right inferior parietal gyrus CSA specifically mediated WHR and WHtR links to cognitive outcomes.

Conclusions: CSA, particularly in the right inferior parietal gyrus, mediates the relationship between obesity metrics and cognitive function. WHtR may be a more reliable marker than BMI or WHR for assessing abdominal obesity's impact on cognition, offering insights into the mechanisms of cognitive deficits in schizophrenia.