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Moderating effect of insulin resistance on the relationship between cortical surface area and cognitive function in

Chen Lin¹, Mengzhuang Gou¹, Shujuan Pan¹

¹Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.

Psychiatry Research. Neuroimaging

|August 19, 2025

Abstract

Objective:

The mechanisms underlying cognitive deficits in schizophrenia remain unclear. Accumulating evidence suggests that insulin resistance (IR) is closely related to brain structure and cognitive impairment. We aimed to determine whether IR mediates or moderates the association between cortical surface area (CSA) and cognitive function in patients with first-episode schizophrenia (PFES).

Methods:

We enrolled 140 PFES and 190 age- and sex-matched healthy controls (HCs). The Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) and the Positive and Negative Symptom Scale were used to assess cognitive function and psychopathology, respectively. The CSA was determined using 3.0-T magnetic resonance imaging. Serum insulin and glucose levels were measured for calculating the Homeostasis Model of Assessment of IR (HOMA-IR) index.

Results:

The MCCB composite score and subscores for the HCs were significantly higher than those for the PFES (P < 0.001). In the PFES, the CSA was significantly positively correlated with the MCCB composite score and with subscores in some domains (P < 0.05). Furthermore, in patients, HOMA-IR positively moderated the association between the left precentral CSA and two MCCB domains: Reasoning and Problem Solving, and Visual Learning. HOMA-IR also positively moderated the association between Verbal Learning and CSA in the left middle temporal gyrus and the right caudal anterior cingulate gyrus (P < 0.05).

Conclusion:

Cognitive deficits were worse in PFES than in HCs. Moreover, HOMA-IR moderated the association between cortical structure and cognitive function, which might provide clues about the mechanisms of cognitive impairment in schizophrenia.

Keywords:

Cognitive function Cortical surface area First-episode Insulin resistance Schizophrenia

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