The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder

Abstract

There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium.