Multivoxel Proton MR Spectroscopy Used to Distinguish Anterior Cingulate Metabolic Abnormalities in Patients with Schizophrenia

Abstract

To test the hypothesis that anterior cingulate cortex (ACC) subregions in patients with schizophrenia are metabolically different from those in healthy control subjects. This institutional review board-approved study was HIPAA compliant, and all participants provided written informed consent. Twenty-two patients with schizophrenia (13 male, nine female; 39.4 years ± 10.6 [standard deviation]) and 11 age- and sex-matched control subjects (seven male, four female; 35.5 years ± 10.7) underwent magnetic resonance (MR) imaging and three-dimensional 3-T voxel proton MR spectroscopy to measure absolute rostral and caudal ACC N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) concentrations. Exact Mann-Whitney test was used to compare patient data with control data, paired-sample Wilcoxon signed rank test was used to compare subregions within groups, and receiver operating characteristic curve analysis was used to assess sensitivity and specificity in diagnosis of schizophrenia. There were no significant metabolic differences between patients and control subjects or between ACC subregions in control subjects. In patients, rostral ACC NAA and Cr concentrations were significantly lower than those in caudal ACC (6.2 mM ± 1.3 vs 7.1 mM ± 1.3, P < .01; 5.7 mmol/L ± 1.4 vs 6.3 mmol/L ± 1.6, P < .01; respectively); however, this did not hold true for Cho concentrations (1.7 mmol/L ± 0.5 vs 1.8 mmol/L ± 0.5). For individual differences between caudal and rostral measurements, only NAA in patients was different from that in control subjects (0.9 mmol/L ± 1.3 vs -0.1 mmol/L ± 0.5, P < .01), enabling prediction of schizophrenia with 68% sensitivity and 91% specificity, for a difference of more than 0.4. Significant differences between caudal and rostral NAA concentration are found in ACC of patients with schizophrenia but not in ACC of healthy control subjects, indicating that neuronal density or integrity differences between ACC subregions may be characteristic of the disease.