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Objective: Reductions in the level of N -acetylaspartate within subcortical structures of patients with obsessive-compulsive disorder (OCD) have been reported in several studies. However, there have been, as yet, no reports regarding N -acetylaspartate levels in the prefrontal cortex of adult drug-naive OCD patients. The authors used proton magnetic resonance spectroscopic imaging ( 1 H-MRSI) to investigate regional N -acetylaspartate level abnormalities and changes after 12 weeks of pharmacotherapy with citalopram in drug-naive OCD patients. Method: Thirteen drug-naive OCD patients and 13 age- and sex-matched healthy comparison subjects were included in this study. N -acetylaspartate levels (obtained from ratios of N -acetylaspartate with creatine, choline, and creatine plus choline) in the prefrontal cortex, parietal cortex, anterior cingulate, posterior cingulate, frontal white matter, and parietal white matter were measured by 1 H-MRSI. In OCD patients, measurements were taken before and after 12 weeks of citalopram treatment. Correlations between N -acetylaspartate concentrations in regions of interest and clinical measures were also assessed. Results: Drug-naive OCD patients exhibited significantly lower N -acetylaspartate levels in the prefrontal cortex, frontal white matter, and anterior cingulate at baseline than did comparison subjects. Significant increases in N -acetylaspartate level were detected in the prefrontal cortex and frontal white matter in OCD patients after 12 weeks of citalopram treatment. Conclusions: These data suggest that reductions in neuronal viability occur in the frontal region of OCD patients and that these reductions may be partly reversible.