Evidence for altered cerebellar vermis neuronal integrity in schizophrenia

To determine if there was evidence for altered neuronal integrity in the cerebellar vermis of patients with schizophrenia, the authors measured N-acetyl-aspartate (NAA, a putative neuronal/axonal marker) using in vivo proton magnetic resonance spectroscopic imaging (1H-MRSI) in 20 chronically medicated male patients with schizophrenia and 15 male comparison subjects. Relative contributions of cerebrospinal fluid, gray matter, and white matter to each MRSI voxel were determined using an MRI tissue segmentation technique. The percentage of tissue was used as a co-variate to determine the extent to which tissue composition contributed to NAA differences. Schizophrenic patients showed significantly decreased NAA and creatine in the anterior cerebellar vermis, independent of differences in voxel tissue composition. Cerebellar NAA levels in control subjects were also significantly correlated with the amount of cerebellar gray matter enclosed in the MRSI voxels, but not in the schizophrenic group. There was no association between cerebellar NAA measures and duration of illness or neuroleptic dose in chlorpromazine equivalents. Reduced NAA in the anterior cerebellar vermis of male patients with schizophrenia supports the hypothesis that cerebellar dysfunction contributes to the pathophysiology of schizophrenia. Furthermore, the lack of a significant correlation between NAA and the amount of cerebellar gray matter in MRSI voxels in the schizophrenic group suggests that NAA levels in both cerebellar gray and white matter are similar in schizophrenic patients, and are presumed to be the result of reduced NAA concentration in the cerebellar gray matter.