Magnetic resonance spectroscopy studies in schizophrenia have revealed consistently reduced N-acetyl aspartate (NAA) levels in chronic patients, but not in recent-onset patients. Studies on the relationship between this marker and disease duration have commonly been negative, although it is also true that they have been conducted in patients with long-standing disease. We compared NAA levels in the dorsolateral prefrontal cortex in 16 recent-onset patients (duration: 1.8+/-0.6 years), 19 chronic patients (duration: 9.7+/-6.1 years), and 20 healthy controls. We studied the NAA/creatine and choline/creatine ratios in the dorsolateral prefrontal cortex in both hemispheres, controlling for the effect of age. Chronic patients had significantly lower NAA/Cr ratios in the left hemisphere compared to recent-onset patients and healthy controls, with no difference in Cho/Cr ratio. There were no differences between controls and recent-onset patients. There was a significant inverse relationship between left-side NAA/Cr and disease duration, suggesting that prefrontal NAA levels may progressively decrease in schizophrenia. Taken within the context of the existing literature, these results indicate that this process may be limited to the early years following the onset of the disease. Therefore, reduced prefrontal levels of NAA may be limited to chronic schizophrenia patients.