A large scale (N=400) investigation of gray matter differences in schizophrenia using optimized voxel-based morphometry

Abstract

Background: Many studies have employed voxel-based morphometry (VBM) of MRI images as an automated method of investigating cortical gray matter differences in schizophrenia. However, results from these studies vary widely, likely due to different methodological or statistical approaches.

Objective: To use VBM to investigate gray matter differences in schizophrenia in a sample significantly larger than any published to date, and to increase statistical power sufficiently to reveal differences missed in smaller analyses.

Methods: Magnetic resonance whole brain images were acquired from four geographic sites, all using the same model 1.5T scanner and software version, and combined to form a sample of 200 patients with both first episode and chronic schizophrenia and 200 healthy controls, matched for age, gender and scanner location. Gray matter concentration was assessed and compared using optimized VBM.

Results: Compared to healthy controls, schizophrenia patients showed significantly less gray matter concentration in multiple cortical and subcortical regions, some previously unreported. Overall, we found lower concentrations of gray matter in regions identified in prior studies, most of which reported only subsets of the affected areas.

Conclusions: Gray matter differences in schizophrenia are most comprehensively elucidated using a large, diverse and representative sample.

Figure 1

Main effect group map with lower GMC (FWE corrected p<0.05, t=5.28) in schizophrenia patients relative to healthy controls.

Figure 2

Direct comparison of GMV and GMC results from the control > patient contrast. Areas in red contain more GM in control subjects, areas in blue contain more GM in schizophrenia patients. One slice from each GMC, GMV, mean and standard error of the mean (SEM) displayed. The GMC contrast has a higher mean and lower SEM than the GMV contrast, which corresponds to decreased statistical power of the latter.

Figure 3

Simultaneous overlay of GM concentration differences between the three major scanner sites (Displayed in green at p< 0.05, F = 18.3, FWE corrected for multiple comparisons.) and diagnosis (Displayed in orange at p<0.05 FWE corrected).