Anterior internal capsule volumes increase in patients with schizophrenia switched from typical antipsychotics to olanzapine

Abnormalities in connectivity are thought to contribute to the symptoms of schizophrenia. Accumulating evidence suggests that antipsychotic medication affects both subcortical and cortical grey and white matter volumes. The goal of this study was to investigate the effects of antipsychotic medication on two white matter tracts: a subcortical-cortical tract, the anterior and posterior limbs of the internal capsule; and a cortical-cortical tract, the corpus callosum. Magnetic resonance imaging was conducted on 10 chronic schizophrenia patients treated with typical antipsychotics and 20 healthy controls at baseline. Patients were switched to olanzapine and both groups were rescanned after 1 year. At baseline, the volume of the anterior limb of the internal capsule was 24% smaller in typical-treated patients than controls (p = 0.009). Patients treated with greater amounts of chlorpromazine-equivalent daily dosage had smaller anterior internal capsule volumes at baseline (r = -0.65, p = 0.04). At follow-up, after being switched to olanzapine, there were no significant differences between patients and controls. Patients with schizophrenia had a significant 25% increase in anterior internal capsule volume from baseline to follow-up compared with controls (p = 0.04). These effects were most prominent in the anterior limb of the internal capsule, which consists of fronto-thalamic pathways, and were not statistically significant in the posterior limb of the internal capsule or corpus callosum. Olanzapine may be effective in normalizing fronto-thalamic structural connectivity in schizophrenia.