Hippocampal pathology in schizophrenia: magnetic resonance imaging and spectroscopy studies

Abstract

The hippocampus is a site of previously reported structural and functional abnormalities in schizophrenia. We used magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) to measure gray matter volumes, the neuronal marker N-acetylaspartate (NAA), and the combination of glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA), designated Glx. Measurements were obtained of the medial temporal lobe, centered on the hippocampus, in 10 male patients with schizophrenia (3 neuroleptic-medicated and 7 medication-free), and 10 matched normal volunteers. MRI volumetric measurements and MRS data obtained with short echo time (TE=20 ms) one-dimensional STEAM chemical shift imaging (CSI) on a GE 1.5 Tesla Signa system were analyzed. A laterality index [(L–R)/(L+R)] was generated from the ratio of Glx to choline-containing compounds (Cho) to test asymmetry changes. Reliability of the MRS measures was assessed with five test–retest studies of healthy volunteers and showed coefficients of variation (CV) in the range of 36–44% for the MRS ratios and standard deviations (S.D.) of 0.15–0.17 for the laterality indices. The Glx/Cho laterality index showed a relative right-sided excess in this region in the patients (−0.23±0.20) compared to the controls (+0.06±0.20), which was not confounded by tissue composition or placement variability of the MRS voxels. Hippocampal volume deficit and asymmetry were not significant, and other MRS measures showed no differences between patients and controls. The preliminary finding of a lateralized abnormality in Glx is consistent with postmortem findings of asymmetric neurochemical temporal lobe abnormalities in schizophrenia.