Gray matter reduction in bilateral insula mediating adverse psychiatric effects of body mass index in schizophrenia

Abstract Background Both schizophrenia (SZ) and overweight/obesity (OWB) have shown some structural alterations in similar brain regions. As higher body mass index (BMI) often contributes to worse psychiatric outcomes in SZ, this study was designed to examine the effects of OWB on gray matter volume (GMV) in patients with SZ. Methods Two hundred fifty subjects were included and stratified into four groups (n = 69, SZ patients with OWB, SZ-OWB; n = 74, SZ patients with normal weight, SZ-NW; n = 54, healthy controls with OWB, HC-OWB; and n = 53, HC with NW, HC-NW). All participants were scanned using high-resolution T1-weighted sequence. The whole-brain voxel-based morphometry was applied to examine the GMV alterations, and a 2 × 2 full factorial analysis of variance was performed to identify the main effects of diagnosis (SZ vs HC), BMI (NW vs OWB) factors, and their interactions. Further, the post hoc analysis was conducted to compare the pairwise differences in GMV alterations. Results The main effects of diagnosis were located in right hippocampus, bilateral insula, rectus, median cingulate/paracingulate gyri and thalamus (SZ < HC); while the main effects of BMI were displayed in right amygdala, left hippocampus, bilateral insula, left lingual gyrus, and right superior temporal gyrus (OWB < NW). There were no significant diagnosis-by-BMI interaction effects in the present study, but the results showed that both SZ and OWB were additively associated with lower GMV in bilateral insula. Moreover, mediation analyses revealed the indirect effect of BMI on negative symptom via GMV reduction in bilateral insula. Conclusion This study further supports that higher BMI is associated with lower GMV, which may increase the risk of unfavourable disease courses in SZ.