Feature Finding Title
Featured Finding Figure
It is unclear to what degree antipsychotic therapy confounds longitudinal imaging studies and postmortem studies of subjects with schizophrenia. To investigate this problem, we developed a non-human primate model of chronic antipsychotic exposure. Three groups of 6 macaque monkeys each were exposed to oral haloperidol, olanzapine or sham for a 17 - 27 month period. The resulting plasma drug levels were comparable to those seen in subjects with schizophrenia treated with these medications. After the exposure, we observed an 8-11% reduction in mean fresh brain weights as well as left cerebrum fresh weights and volumes in both drug-treated groups compared to sham animals. The fresh brain weights for the sham (S), haloperidol (H) and olanzapine (O) exposed monkeys are shown in the figure. The horizontal bars indicate group means. The differences were observed across all major brain regions (frontal, parietal, temporal, occipital and cerebellum), but appeared most robust in the frontal and parietal regions. Stereological analysis of the parietal region using Cavalieri's principle revealed similar volume reductions in both grey and white matter. In addition, we assessed the subsequent tissue shrinkage due to standard histological processing and found no evidence of differential shrinkage due to drug exposure. However, we observed a pronounced general shrinkage effect of ~20% and a highly significant variation in shrinkage across brain regions. In conclusion, chronic exposure of non-human primates to antipsychotics was associated with reduced brain volume. Antipsychotic medication may confound postmortem studies and longitudinal imaging studies of subjects with schizophrenia that depend upon volumetric measures.
Dorph-Petersen KA, Pierri JN, Perel JM, Sun Z, Sampson AR, Lewis DA: The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: A comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology 30: 1649-1661, 2005.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
Pittsburgh, Pennsylvania 15213-2593
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