Patterns of Gray Matter Abnormalities in Schizophrenia Based on an International Mega-analysis

Abstract

Analyses of gray matter concentration (GMC) deficits in patients with schizophrenia (Sz) have identified robust changes throughout the cortex. We assessed the relationships between diagnosis, overall symptom severity, and patterns of gray matter in the largest aggregated structural imaging dataset to date. We performed both source-based morphometry (SBM) and voxel-based morphometry (VBM) analyses on GMC images from 784 Sz and 936 controls (Ct) across 23 scanning sites in Europe and the United States. After correcting for age, gender, site, and diagnosis by site interactions, SBM analyses showed 9 patterns of diagnostic differences. They comprised separate cortical, subcortical, and cerebellar regions. Seven patterns showed greater GMC in Ct than Sz, while 2 (brainstem and cerebellum) showed greater GMC for Sz. The greatest GMC deficit was in a single pattern comprising regions in the superior temporal gyrus, inferior frontal gyrus, and medial frontal cortex, which replicated over analyses of data subsets. VBM analyses identified overall cortical GMC loss and one small cluster of increased GMC in Sz, which overlapped with the SBM brainstem component. We found no significant association between the component loadings and symptom severity in either analysis. This mega-analysis confirms that the commonly found GMC loss in Sz in the anterior temporal lobe, insula, and medial frontal lobe form a single, consistent spatial pattern even in such a diverse dataset. The separation of GMC loss into robust, repeatable spatial patterns across multiple datasets paves the way for the application of these methods to identify subtle genetic and clinical cohort effects.

Keywords: independent component analysis; schizophrenia; source-based morphometry; symptoms; voxel-based morphometry.

Fig. 1.

Spatial maps of the 9 components showing (Ct/Sz) group effect, ordered by decreasing effect size from the primary SBM decomposition. All are thresholded at |z| > 2.5. The color bar indicates the color mapping for the normalized component weights. Ct, control; SBM, source-based morphometry; Sz, schizophrenia.

Fig. 2.

Results of the VBM analysis; voxels above |Z| > 2.5 are shown. (a) Significant clusters where Ct > Sz. (b) Significant clusters where Sz > Ct. Ct, control; Sz, schizophrenia; VBM, voxel-based morphometry.