Metabolic Abnormalities in the Hippocampus of Patients with Schizophrenia: A 3D Multivoxel MR Spectroscopic Imaging Study at 3T

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Nineteen patients with schizophrenia and 11 matched healthy controls underwent MR imaging and multivoxel point-resolved 1H-MRS at 3T to obtain their hippocampal gray matter absolute NAA, Cr, and Cho concentrations. Patients’ average hippocampal GM Cr concentrations were 19% higher than those of controls. NAA and Cho showed no differences. The authors conclude that the findings suggest the hippocampal volume deficit in schizophrenia is not due to net loss of neurons, which is in agreement with histopathology studies but not with prior 1H-MR spectroscopy reports. Elevated Cr would be consistent with hippocampal hypermetabolism.

Abstract

Figure 2 from paper
Upper: A, Axial MPRAGE image from a 51-year-old female patient (16 in Table 1) superimposed on the VOI (in yellow). Orange lines show the 9 × 6 voxel CSI grid; voxels that passed the selection criteria to calculate the NAA concentration are highlighted in transparent red. B–D, SPM12-generated WM (B), GM (C), and CSF (D) masks also superimposed on the VOI CSI grid and selected voxels. Note the n ≥ 2 voxels that “passed” the selection criteria described in the “Materials and Methods” section.

BACKGROUND AND PURPOSE

Schizophrenia is well-known to be associated with hippocampal structural abnormalities. We used 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 hippocampal GM absolute 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.

 

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Metabolic Abnormalities in the Hippocampus of Patients with Schizophrenia: A 3D Multivoxel MR Spectroscopic Imaging Study at 3T
Jeffrey Ross
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