Regionally Specific Neuronal Pathology in Untreated Patients with Schizophrenia: A Proton Magnetic Resonance Spectroscopic Imaging Study

BACKGROUND Proton magnetic resonance spectroscopic imaging (1H-MRSI) studies have reported reductions of N-acetyl aspartate (NAA), a marker of neuronal integrity, in the hippocampal region (HIPPO) and dorsolateral prefrontal cortex (DLPFC) of pharmacologically treated patients with schizophrenia. The purpose of the present study was twofold: to exclude drug treatment as a source of the previous findings and to examine NAA relative concentrations in a unique sample of chronically untreated patients. METHODS We studied 12 medication-free patients, 5 of whom were "drug naive" and symptomatic for a mean of 12 years, and 12 control subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined [i.e., NAA/creatine (CRE), NAA/choline (CHO), CHO/CRE] for multiple cortical and subcortical regions. Hippocampal formation and frontal lobe volumes were also measured to test for correlations with 1H-MRSI data. RESULTS Significant reductions of NAA/CRE and NAA/CHO were found bilaterally in HIPPO and DLPFC. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios, length of illness, and volumes of the hippocampal region and frontal lobe. Mean ratios and effect sizes were not different in chronically ill but still medication-naive patients in comparison with subacute patients and previously studied chronic patients receiving medications. CONCLUSIONS Bilateral reductions of NAA ratios in HIPPO and DLPFC are reliable findings. The findings implicate a relatively localized pattern of neurochemical pathology that does not appear to change with prolonged illness whether medicated or unmedicated.