Cerebro-cerebellar gray matter abnormalities associated with cognitive impairment in patients with recent-onset and chronic schizophrenia

Abstract

Although the role of the cerebellum in schizophrenia has gained attention, its contribution to cognitive impairment remains unclear. We aimed to investigate volumetric alterations in the cerebro-cerebellar gray matter (GM) in patients with recent-onset schizophrenia (ROS) and chronic schizophrenia (CS) compared with healthy controls (HCs). Seventy-two ROS, 43 CS, and 127 HC participants were recruited, and high-resolution T1-weighted structural magnetic resonance images of the brain were acquired. We compared cerebellar GM volumes among the groups using voxel-based morphometry and examined the cerebro-cerebellar GM volumetric correlations in participants with schizophrenia. Exploratory correlation analysis investigated the functional relevance of cerebro-cerebellar GM volume alterations to cognitive function in the schizophrenia group. The ROS and CS participants demonstrated smaller cerebellar GM volumes, particularly in Crus I and II, than HCs. Extracted cerebellar GM volumes demonstrated significant positive correlations with the cerebral GM volume in the fronto-temporo-parietal association areas engaged in higher-order association. The exploratory analysis showed that smaller cerebellar GM in the posterior lobe regions was associated with poorer cognitive performance in participants with schizophrenia. Our study suggests that cerebellar pathogenesis is present in the early stages of schizophrenia and interconnected with structural abnormalities in the cerebral cortex. Integrating the cerebellum into the pathogenesis of schizophrenia will help advance our understanding of the disease and identify novel treatment targets concerning dysfunctional cerebro-cerebellar interactions.

Fig. 1. Cerebellar VBM and post-hoc comparisons between the ROS, CS, and HC groups.

A Results of cerebellar VBM displaying significant between-group differences in GM volume among the ROS, CS, and HC groups (FWE-corrected voxel-wise p < 0.05 with a minimum of 100 contiguous voxels). B Significant cerebellar clusters visualized on a flat map. C Post-hoc pairwise comparisons within significant cerebellar clusters. VBM voxel-based morphometry; GM gray matter; ROS recent-onset schizophrenia; CS chronic schizophrenia; HC healthy control; FWE family-wise error.

Fig. 2

Cerebro-cerebellar gray matter volumetric associations in the participants with schizophrenia (cluster-forming threshold of p < 0.0001; cluster-wise threshold of p < 0.05).