Altered interhemispheric and temporal lobe white matter microstructural organization in severe chronic schizophrenia

Abstract

Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. Using tract-based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia. Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age- and gender-matched healthy controls using a 64 gradient direction sequence, (b=1300 s/mm(2)) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion-weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin.

Figure 1

Regions of reduced fractional anisotropy (FA) in the schizophrenia relative to the control group. Clusters of voxels (p<0.05, threshold-free cluster enhancement, TFCE) with significantly reduced FA in chronic schizophrenia compared with controls in (a) the genu, body, and splenium of the corpus callosum, (b) the body of the corpus callosum and the superior longitudinal fasciculus (SLF) (more prominent on the right), and (c) in the ILF. Significant clusters (p<0.05, TFCE) are denoted in a red (p=0.05) to yellow (lowest p-value) color intensity scale given at the bottom of the figure and in radiological format.

Figure 2

Regions where radial diffusivity (RD) was higher in the schizophrenia than the control group in the (a) genu and splenium of corpus callosum, (b) body of the corpus callosum and R-SLF, and (c) in the R-ILF. Increased RD in the chronic schizophrenia compared with the control group were evident in the genu (726 mm³, T=0.31–3.64, median=1.78), body (1421 mm³, T=0.38–3.98, median=1.87), and splenium (723 mm³, T=0.23–4.22, median=2.06) of the corpus callosum (p<0.05, threshold-free cluster enhancement, TFCE). Significant clusters (p<0.05, TFCE) are denoted in a blue (p=0.05) to light blue (lowest p-value) color intensity scale given at the bottom of the figure and in radiological format.

Figure 3

(a) Median fractional anisotropy (FA) is reduced in three regions of the corpus callosum in the schizophrenia (squares) compared with control subjects (circle). (b) Correlation of the splenium FA and illness duration in chronic schizophrenia. (a) Reduced FA in the genu (1309 mm³, T=0.79–3.9, median=1.78), body (2069 mm³, T=0.79–5.2, median=1.87), and splenium (723 mm³, T=0.70–3.8, median=1.50) of the corpus callosum in the schizophrenia (squares) compared with control subjects (circle). (b) Correlation of the splenium FA and illness duration in chronic schizophrenia.