Alterations of white matter connectivity in first episode schizophrenia

Abstract

Cerebral disconnectivity due to white matter alterations in patients with chronic schizophrenia assessed by diffusion tensor imaging has been reported previously. The aim of this preliminary study is to investigate whether cerebral disconnectivity can be detected as early as the first episode of schizophrenia. Intervoxel coherence values were compared by voxel-based t test in 12 patients with first episode schizophrenia and 12 age- and gender-matched control groups. We detected 14 circumscribed significant clusters (P < 0.02), 3 of them with higher, and 11 of them with lower IC values for patients with schizophrenia than for healthy control groups. We interpret these white matter alterations in different regions to be disconnected fiber tracts already present early in schizophrenic disease progression.

Introduction

Schizophrenia has been described as a disorder of disrupted connectivity in the fronto-thalamo-striato-cerebellar circuit (Andreasen et al., 1998). The basis of impaired connectivity may be subtle gray and white matter lesions, as described by several investigators (Shenton et al., 2001). Diffusion tensor imaging (DTI) is a relatively new approach to assessing tissue structure and geometry at a microscopic level. It measures diffusion-driven displacements of molecules during their random path along axonal fibers, expressed as fractional anisotropy (FA) or intervoxel coherence (IC) ranging from 0 (isotropic medium) to 1 (fully anisotropic medium). IC guarantees a very robust signal-to-noise ratio and considers the degree of collinearity between the diffusion tensor of the reference voxel and the adjacent voxels (Pierpaoli and Basser, 1996, Pfefferbaum et al., 2000); in literature, IC is also labeled as Coherence Index (Deutsch et al., 2005). IC is a measure similar to FA (Klingberg et al., 1999, Klingberg et al., 2000). It is related to FA value; high IC value indicates both the local strength of FA and the agreement of fiber direction in neighboring voxels (Deutsch et al., 2005). In both studies, the main orientation of major fiber tracts important for reading and spelling were reported using FA and IC measures. Previous studies have shown a reduced FA in schizophrenia (Agartz et al., 2001, Ardekani et al., 2003, Buchsbaum et al., 1998, Burns et al., 2003, Foong et al., 2000, Hubl et al., 2004, Kubicki et al., 2003, Kubicki et al., 2005, Kumra et al., 2004, Lim et al., 1999, Minami et al., 2003, Okugawa et al., 2004, Sun et al., 2003, Wang et al., 2004). Only one study reported augmented FA in circumscribed tracts of the brain in hallucinating, chronic schizophrenic patients as compared with FA in healthy control groups (Hubl et al., 2004). Using FA in first episode schizophrenia, two studies found no differences compared to healthy controls in the hippocampus (Begre et al., 2003) or the splenium and genu of corpus callosum (Price et al., 2005). Using IC, two studies of the same group compared amygdale and entorhinal regions in chronic schizophrenia patients to healthy controls (Kalus et al., 2005a, Kalus et al., 2005b). To our knowledge, IC has never been used to investigate white matter in first episode schizophrenic patients. Several studies suggest that schizophrenia is a progressive disease accompanied by loss of gray and white matter volume (Cahn et al., 2002, Gogtay et al., 2004, Velakoulis et al., 2002). However, it is not clear whether changes in white matter structure exist from childhood, prior to the first psychotic symptoms, or develop during disease progression. To investigate whether previously described anisotropy changes of white matter in chronic schizophrenia are present at the beginning of the schizophrenic course, we measured IC as an indication of connectivity in 12 first episode psychosis patients. We used 12 age- and gender-matched subjects as the control group. From previous results of studies in chronic schizophrenia using FA, we expected to find clusters of reduced IC in corpus callosum, cingulum, main white matter fascicles, as well as in frontal, temporal, and occipital white matter regions.