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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.

SUBMITTER: Hardy CJ

PROVIDER: S-EPMC3198217 | biostudies-other | 2011 Nov

REPOSITORIES: biostudies-other

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Project description:AimsAccumulated evidence indicates that cerebral metabolic features, evaluated by proton magnetic resonance spectroscopy (1 H-MRS), are sensitive to early mitochondrion dysfunction associated with mitochondrial encephalomyopathy (ME). The metabolite ratios of lactate (lac)/Cr, N-acetyl aspartate (NAA)/creatine (Cr), total choline (tCho)/Cr, and myoinositol (mI)/Cr are measured in the infarct-like lesions by 1 H-MRS and may reveal metabolic changes associated with ME. However, the application of this molecular imaging technique in the investigation of the pathology of ME subtypes is unknown.MethodsIn this study, cerebral metabolic features of pathologically diagnosed ME cases, that is, 19 mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); nine chronic progressive external ophthalmoplegia (CPEO); and 23 healthy controls, were investigated using 1 H-MRS. Receiver operating characteristics (ROC) analysis was used to evaluate the diagnostic power of the cerebral metabolites. Histochemical evaluation was carried out on muscle tissues derived from biopsy to assess the abnormal mitochondrial proliferation. The association between cerebral metabolic and mitochondrial cytopathy was examined by correlation analysis.ResultsPatients with MELAS or CPEO exhibited a significantly higher Lac/Cr ratio and a lower NAA/Cr ratio compared with controls. The ROC curve of Lac/Cr ratio indicated prominent discrimination between MELAS or CPEO and healthy control subjects, whereas the NAA/Cr ratio may present diagnostic power in the distinction of MELAS from CPEO. Lower NAA/Cr ratio was associated with higher Lac/Cr in MELAS, but not in CPEO. Furthermore, higher ragged-red fibers (RRFs) percentages were associated with elevated Lac/Cr and reduced NAA/Cr ratios, notably in MELAS. This association was not noted in the case of mI/Cr ratio.ConclusionsMitochondrial cytopathy (lactic acidosis and RRFs on muscle biopsy) was associated with neuronal viability but not glial proliferation, notably in MELAS. Mitochondrial neuronopathy and neuronal vulnerability are considered significant causes in the pathogenesis of MELAS, particularly with regard to stroke-like episodes.

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Multivoxel proton MR spectroscopy used to distinguish anterior cingulate metabolic abnormalities in patients with schizophrenia.

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