Proton magnetic resonance spectroscopic imaging of gray and white matter in bipolar-I and schizophrenia

Background: Glutamine plus glutamate (Glx), as well as N-acetylaspartate compounds, (NAAc), a marker of neuronal viability, are quantified with proton magnetic resonance spectroscopy (H-1-MRS) and have been reported altered in psychotic disorders. However, few studies have compared these neurometabolites in bipolar disorder and schizophrenia. Methods: Used H-1-MRS imaging from an axial supraventricular slab of gray matter (GM; medial-frontal and medial-parietal) and white matter (WM; bilateral-frontal and bilateral-parietal) voxels. Bipolar-I with history of psychosis (N = 43), schizophrenia (N = 41) and healthy controls (HC; N = 45) were studied (age range: 17-65). Results: Amongst younger (age = 40 years-median split) bipolar-I vs HC subjects Glx was increased (p < 0.001), while NAAc was reduced in WM (p < 0.001). In GM, NAAc (p < 0.001) and myo-inositol (p = 0.002) were reduced. Amongst older bipolar-I (vs HC) in WM regions we found reductions in: NAAc (p < 0.001), glycerophospho-choline + phospho-choline (p < 0.001), creatine + phospho-creatine (p<0.001) and myo-inositol (p<0.001); in GM only Glx was increased (p<0.005). Contrasts between bipolar-I and schizophrenia produced fewer results: amongst younger subjects, reduced NAAc (p<0.001) in WM and lower myo-inositol in GM (p = 0.04) in bipolar-I vs schizophrenia. In the older patients, bipolar-I had lower GM NAAc (p = 0.009) than schizophrenia. Limitations: First, differential exposure to antipsychotic and mood stabilizing medication across the groups. Second, differences in substance use histories among the groups. Third, neglect of peripheral and ventral cortical and subcortical regions. Finally, limited power to detect bipolar/schizophrenia differences. Conclusions: Chronically-treated bipolar-I have increased Glx and reduced NAAc, suggestive of neuronal dysfunction. The NAAc reductions are more severe in bipolar-I than in schizophrenia patients.