Effect of clozapine on white matter integrity in patients with schizophrenia: a diffusion tensor imaging study

Abstract

Several diffusion tensor imaging (DTI) studies have reported disturbed white matter integrity in various brain regions in patients with schizophrenia, whereas only a few studied the effect of antipsychotics on DTI measures. The aim of this study was to investigate the effect of 12 weeks of clozapine treatment on DTI findings in patients with schizophrenia, and to compare the findings with those in unaffected controls. The study included 16 patients with schizophrenia who were assessed with the Positive and Negative Syndrome Scale, a neurocognitive test battery, and DTI at baseline and 12 weeks after the initiation of clozapine treatment. Eight unaffected controls were assessed once with the neurocognitive test battery and DTI. Voxel-wise analysis of DTI data was performed via tract-based spatial statistics (TBSS). Compared with the control group, the patient group exhibited lower fractional anisotropy (FA) in 16 brain regions, including the bilateral superior longitudinal fasciculi, inferior fronto-occipital fasciculi, superior and inferior parietal lobules, cingulate bundles, cerebellum, middle cerebellar peduncles, and left inferior longitudinal fasciculus, whereas the patients had higher FA in six regions, including the right parahippocampus, left anterior thalamic radiation, and right posterior limb of the internal capsule before clozapine treatment. After 12 weeks of treatment with clozapine, white matter FA was increased in widespread brain regions. In two of the regions where FA had initially been lower in patients compared with controls (left inferior fronto-occipital fasciculus and superior parietal lobule), clozapine appeared to increase FA. An improvement in semantic fluency was correlated with the increase in FA value in the left inferior fronto-occipital fasciculus. An increase in FA following 12 weeks of treatment with clozapine suggests that this treatment alters white matter microstructural integrity in patients with schizophrenia previously treated with typical and/or atypical antipsychotics and, in some locations, reverses a previous deficit.

Keywords: Clozapine; Diffusion tensor imaging; Fractional anisotropy; Schizophrenia; White matter.