Focal white matter density changes in schizophrenia: reduced inter-hemispheric connectivity.

Gray matter changes have been demonstrated in several regions in schizophrenia. Particularly, the frontal and temporal cortices and amygdala-hippocampal region have been found decreased in volume and density in magnetic resonance imaging (MRI) studies. These abnormalities may reflect an aberrant neuronal network in schizophrenia, suggesting that white matter fibers connecting these regions may also be affected. However, it is unclear if particular white matter areas are (progressively) affected in schizophrenia and if these are related to the gray matter changes. Focal white matter changes in schizophrenia were studied in whole brain magnetic resonance images acquired from 159 patients with schizophrenia or schizophreniform disorder and 158 healthy comparison subjects using voxel-based morphometry. White matter density changes in the patients with schizophrenia were correlated to gray matter density changes and to illness severity. In the patients with schizophrenia, significant decreases in white matter density were found in the genu and truncus of the corpus callosum in the left and right hemisphere, in the right anterior internal capsule and in the right anterior commissure. No interactions between diagnosis and age were found. Increased illness severity was correlated with low density of the corpus callosum and anterior commissure. Decreased corpus callosum density correlated with decreased density of thalamus, lateral inferior frontal and insular gray matter in patients and controls and with decreased density of medial orbitofrontal and superior temporal gyri in patients. Decreased internal capsule and anterior commissure density correlated with increased caudate, and globus pallidus density in patients and controls. These findings suggest aberrant inter-hemispheric connectivity of anterior cortical and sub-cortical brain regions in schizophrenia, reflecting decreased hemispheric specialisation in schizophrenia.