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 largely unknown. Studies in animals have suggested that antipsychotics modify the expression of various intraneuronal proteins, but no analogous in vivo data in humans are available. The objective of the present study was to assess whether antipsychotics modify N-acetylaspartate (an intraneuronal marker of neuronal functional integrity) measures in brains of patients with schizophrenia.


METHODS
We used proton magnetic resonance spectroscopic imaging to study 23 patients with schizophrenia (DSM-IV diagnosis) using a within-subject design. Patients were studied twice: once while on a stable regimen of antipsychotic drug treatment (for at least 4 weeks) and once while off medication for at least 2 weeks. Several cortical and subcortical regions were assessed, including the dorsolateral prefrontal cortex and the hippocampal area.


RESULTS
Analysis of variance showed that, while on antipsychotics, patients had significantly higher N-acetylaspartate measures in the dorsolateral prefrontal cortex (p =.002). No other region showed any significant effect of treatment.


CONCLUSIONS
These results indicate that antipsychotic drugs increase N-acetylaspartate measures selectively in the dorsolateral prefrontal cortices of patients with schizophrenia, suggesting that these drugs modify in a regionally specific manner the function of a population of cortical neurons. N-Acetylaspartate measures may provide a useful tool to further investigate the effects of antipsychotics at the intracellular level.
Bertolino
A
A
Clinical Brain Disorders Branch, Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Room 4S235 (MSC 1379), Bethesda, MD 20892, USA.
Callicott
J H
JH
Mattay
V S
VS
Weidenhammer
K M
KM
Rakow
R
R
Egan
M F
MF
Weinberger
D R
DR
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D014150:Antipsychotic Agents; D001224:Aspartic Acid; C000179:N-acetylaspartate