Structural brain abnormalities, such as reductions in gray matter volume, have been consistently described in patients with schizophrenia, according to background information in the article. The current study was designed to test whether patients treated with an atypical antipsychotic medication (olanzapine) would have less reduction in gray matter volume than patients treated with a conventional antipsychotic medication (haloperidol), and whether these changes are associated with changes in disturbed thinking and general mental functioning.

Jeffrey A. Lieberman, M.D., of the University of North Carolina Medical School, Chapel Hill, at the time of the study, and colleagues studied 161 patients who were randomly assigned treatment with either haloperidol or olanzapine at the time of a first psychotic episode (baseline). Patients underwent neurocognitive testing and magnetic resonance imaging (MRI) assessments at baseline, and then at 12, 24, 52 and 104 weeks of treatment in a five-year longitudinal study conducted at 14 academic medical centers. A matched sample of 58 healthy volunteers underwent MRI and were compared on brain volume measures.

"The principle new finding of this study is the significant difference in the course and magnitude of these changes between patients treated with haloperidol, a conventional antipsychotic, and olanzapine, an atypical antipsychotic," the authors report. "Specifically, olanzapine was associated with less such change in brain volume during and in the aftermath of the first psychotic episode. These differences in volume change were highlighted by the comparison with healthy volunteers, which showed no significant reductions in gray matter volume and a trajectory similar to that of the olanzapine group."

"The associations between greater decrease in WBGM [whole brain gray matter] and less improvement in neurocognitve functioning [general mental functioning], and greater improvements on PANSS total and negative subscales [a measure of disturbed thinking] with less increase in lateral ventricular volume indicate that treatment effects on brain volume and the behavioral pathology of the illness may be associated," the authors write.

"Although these results must be confirmed, they suggest that a significant difference exists between a typical antipsychotic (haloperidol) and an atypical agent (olanzapine) that is due to either a safety or efficacy advantage and reflected by a differential pattern of brain volume change and clinical response," the authors conclude. "Future clinical studies should attempt to verify whether the early stage of psychosis is associated with brain volume changes and whether antipsychotics can neurobiologically alter the course of the disease."

(Arch Gen Psychiatry. 2005;62:361-370. Available post-embargo at archgenpsychiatry.com)

Editor's Note: This study was supported by Lilly Research Laboratories, Indianapolis, Ind.; Public Health Service and other grants from the National Institute of Mental Health, National Institute of Health, Bethesda, Md.; the University of North Carolina Mental Health and Neuroscience Clinical Research Center, Chapel Hill; the North Carolina Foundation of Hope, Raleigh; and the National Alliance for Research on Schizophrenia and Depression (NARSAD) Foundation, Great Neck, N.Y.

Note: If no author is given, the source is cited instead.

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