The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia

Background: The specific intracellular effects of antipsychotic drugs are l argely unknown, Studies in animals have suggested that antipsychotics modif y the expression of various intraneuronal proteins, but no analogous in viv o data in humans are available. The; objective of the present study was to assess whether antipsychotics modify N-acetylaspartate tan intraneuronal ma rker of neuronal functional integrity) measures in brains of patients with schizophrenia. Methods: We used proton magnetic resonance spectroscopic imaging to study 2 3 patients with schizophrenia (DSM-IV diagnosis) using a within-subject des ign. Patients were studied twice: once while on a stable regimen of antipsy chotic drug treatment (for at least 4 weeks) and once while off medication for at least 2 weeks. Several cortical and subcortical regions were assesse d, including the dorsolateral prefrontal cortex and the hippocampal area. Results: Analysis of variance showed that, while on antipsychotics, patient s had significantly higher N-acetylaspartate measures in the dorsolateral p refrontal cortex (p =.002). No other region showed any significant effect o f treatment. Conclusions: These results indicate that antipsychotic drugs increase N-ace tylaspartate measures selectively in the dorsolateral prefrontal cortices o f patients with schizophrenia, suggesting that these drugs modify in a regi onally specific manner the function of a population of cortical neurons. N- Acetylaspartate measures may provide a useful tool to further investigate t he effects of antipsychotics at the intracellular level. Biol Psychiatry 20 01;49:39-46 (C) 2001 Society of Biological Psychiatry.