Metabolic abnormalities in the hippocampus of patients with schizophrenia: A 3D multivoxel MR spectroscopic imaging study at 3T

BACKGROUNDANDPURPOSE: Schizophrenia is well-known to be associated with hippocampal structural abnormalities.Weused 1H-MR spectroscopy to test the hypothesis that these abnormalities are accompanied by NAA deficits, reflecting neuronal dysfunction, in patients compared with healthy controls. MATERIALS AND METHODS: Nineteen patients with schizophrenia (11 men; mean age, 40.6±10.1 years; mean disease duration, 19.5±10.5 years) and 11 matched healthy controls (5 men; mean age, 33.7 ± 10.1 years) underwent MR imaging and multivoxel point-resolved spectroscopy (TE/TR, 35/1400 ms) 1H-MRS at 3T to obtain their hippocampalGMabsolute NAA, Cr, Cho, and mIns concentrations. Unequal variance t tests and ANCOVA were used to compare patients with controls. Bilateral volumes from manually outlined hippocampal masks were compared by using unequal variance t tests. RESULTS: Patients' average hippocampal GM Cr concentrations were 19% higher than that of controls, 8.7 ± 2.2 versus 7.4 ± 1.2 mmol/L (P≤.05); showing no differences, concentrations in NAA were 8.8±1.6 versus 8.7±1.2 mmol/L; in Cho, 2.3±0.7 versus 2.1±0.3 mmol/L; and in mIns, 6.1±1.5 versus 5.2±0.9 (all P≤.1). There was a positive correlation between mIns and Cr in patients (r=0.57, P≤.05) but not in controls. The mean bilateral hippocampal volume was 10% lower in patients: 7.5 ± 0.9 versus 8.4± 0.7 cm3 (P ≤ .05). CONCLUSIONS: These findings suggest that the hippocampal volume deficit in schizophrenia is not due to net loss of neurons, in agreement with histopathology studies but not with prior 1H-MR spectroscopy reports. Elevated Cr is consistent with hippocampal hypermetabolism, and its correlation with mIns may also suggest an inflammatory process affecting some cases; these findings may suggest treatment targets and markers to monitor them.