Effects of chronic haloperidol and clozapine treatments on frontal and caudate neurochemistry in schizophrenia

N-Acetyl-aspartate (NAA), a marker of neuronal integrity, has been found to be reduced in frontal regions in schizophrenia. However, the impact of ant ipsychotic drug type on NAA has not been carefully evaluated. We studied ou tpatients with schizophrenia/schizoaffective disorders chronically treated with haloperidol or clozapine and normal controls with single-voxel H-1-MRS of the caudate nuclei and the left frontal lobe. Concentrations of NAA, ch oline containing compounds (Cho) and creatine plus phosphocreatine (Cre) we re determined and corrected for the proportion of cerebrospinal fluid (CSF) in each voxel. The haloperidol-treated group had significantly lower CSF-u ncorrected and CSF-corrected left frontal NAA than the normal controls, wit h the clozapine group having intermediate concentrations. The haloperidol-t reated group had significantly lower CSF-uncorrected caudate NAA than the n ormal controls, but the three groups did not differ after correcting for CS F fraction. Performance times in the Grooved Pegboard, a measure of motor d exterity and proxy for parkinsonism, were correlated with CSF-uncorrected a nd CSF-correctcd left frontal NAA. Demographic and illness-related variable s were not related to NAA. Exposure to haloperidol-like drugs may in part a ccount for the frontal NAA reductions previously reported in schizophrenia. Adjustment for proportion of voxel CSF should he considered in H-1-MRS stu dies. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.