Selective deficit of hippocampal N-acetylaspartate in antipsychotic-naive patients with schizophrenia

Background: Studies using proton magnetic resonance spectroscopy in schizophrenia have demonstrated abnormality of N-acetylaspartate but are confounded by the effects of phase of illness and medication. There is mounting evidence that antipsychotic medication influences N-acetylaspartate. Methods: A group of first-episode patients who had received no, or minimal, antipsychotic medication was examined at baseline and after 3 months treatment. Normal comparison subjects were examined at the same interval. Ratios of N-acetylaspartate, creatine plus phosphocreatine, and choline-containing compounds in the left prefrontal cortex, hippocampus, and basal ganglia were measured. Results: The mean duration of symptoms for all patients was 31.6 (SD 26.1) weeks. A significant reduction of hippocampal N-acetylaspartate/creatine plus phosphocreatine was found in the antipsychotic-naive group relative to those previously treated and to controls at baseline (F=7.3, p<.002). No group differences were found at follow-up. Conclusions: Hippocampal N-acetylaspartate/creatine plus phosphocreatine appears to be selectively affected early in the course of illness. The finding of neurochemical differences between treatment naive and previously treated patients confirms the relevance of medication status in proton magnetic resonance spectroscopy studies. Further investigation of the influence of medication at this stage of illness is warranted.