Lower concentration of hippocampal N-acetylaspartate in familial bipolar I disorder.

OBJECTIVE: Previous studies attempting to identify neuropathological alterations in the hippocampus in bipolar disorder have been inconclusive. The objective of this study was to determine if the concentration of N-acetylaspartate, a neuronal and axonal marker, was lower in subjects with familial bipolar I disorder than in healthy comparison subjects, suggesting possible neuronal loss, neuronal dysfunction, or neuropil reduction in bipolar I disorder. METHOD: N-acetylaspartate, choline, and creatine in the right and left hippocampus were measured in 15 euthymic male patients with familial bipolar I disorder and 20 healthy male comparison subjects by using proton magnetic resonance spectroscopy ((1)H-MRS). RESULTS: Relative to the comparison group, the patients with bipolar I disorder demonstrated significantly lower concentrations of N-acetylaspartate and creatine but normal choline concentration in both the right and left hippocampus. There were no group or lateralized differences in the percentages of different tissue types within the MRS voxels, suggesting that the hippocampal N-acetylaspartate and creatine alterations were not an artifact of variations in tissue types represented in the voxels. There was also a significant negative correlation between N-acetylaspartate concentration in the right hippocampus and illness duration, after adjustment for the effects of age. CONCLUSIONS: This preliminary study provides support for the existence of neuronal loss, neuronal metabolic dysfunction, or interneuronal neuropil reduction in the hippocampal region in male patients with familial bipolar I disorder. The finding of normal hippocampal choline levels in these patients does not provide support for ongoing myelin breakdown or glial cell proliferation in this brain region in familial bipolar I disorder. The significant association between illness duration and N-acetylaspartate concentration in the right hippocampus supports the idea that neuronal pathology may increase with disease progression and that this effect may be lateralized, involving the right but not the left hippocampus.

Anterior hippocampal volume reduction in male patients with schizophrenia.

Quantitative high resolution magnetic resonance imaging (MRI) was utilized to measure anterior, posterior, and total hippocampal volumes in 27 male patients with chronic schizophrenia and 24 male controls. To optimize measurement techniques, hippocampal volumes were: (1) acquired with 1.4-mm slices; (2) excluded with the amygdala; (3) normalized for position; and (4) corrected for total intracranial volume (ICV). The results of a linear mixed effects regression analysis, which made it possible to analyze total anterior and total posterior hippocampal volumes separately, indicated that the anterior hippocampus was significantly smaller in the schizophrenic group relative to the control group. There were no significant group differences with respect to posterior hippocampal volumes, and no significant correlations between hippocampal volumes and illness duration. A significant lateralized asymmetry was also noted in both groups with the right hippocampal volume being larger than the left. These preliminary findings support a significant anterior hippocampal volume reduction in men with schizophrenia as well as a similar hippocampal volume asymmetry in both male controls and schizophrenics.