Reduced white matter integrity correlated with cortico-subcortical gray matter deficits in schizophrenia

Background: The pathology of schizophrenia is thought to involve multiple brain regions and the connections among them. Although a number of MRI studies have demonstrated gray matter reductions and abnormal white matter integrity in schizophrenia, to date no study has investigated their association in the whole brain. Methods: Twenty-seven schizophrenia patients and 33 healthy controls were recruited. Voxelwise group comparison of white matter fractional anisotropy (FA) was performed using tract-based spatial statistics (TBSS). Comparison of gray matter concentration (GMC) was performed using voxel-based morphometry (VBM). Voxelwise correlational analyses were performed for patients inside a significant GMC reduction mask created by VBM, using simple regression models with mean FA values of each significant TBSS cluster as explanatory variables. Results: TBSS revealed FA reduction in left prefrontal and occipital regions in the patients. Mean FA values of both areas revealed significant correlation with gray matter reduction in multiple cortical and subcortical areas, with overlapping but different patterns. Conclusions: Voxelwise correlational analysis of white and gray matter pathology, as performed here, further elucidated the pathophysiology of schizophrenia, and provided a novel view of the "disconnection hypothesis" of schizophrenia. (C) 2009 Elsevier B.V. All rights reserved.