Neuronal pathology in the hippocampal area of patients with bipolar disorder: A study with proton magnetic resonance spectroscopic imaging

Background: The brain regions involved in the pathophysiology of bipolar disorder have not been definitively determined. Previous studies have suggested possible involvement of the hippocampus and of prefrontal regions. Proton magnetic resonance spectroscopic imaging (¹H-MRSI) allows measurement of N-acetylaspartate (NAA, marker of neuronal integrity), choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) in multiple brain regions. The objective of this study was to assess possible NAA reductions in hippocampus and prefrontal regions in patients with bipolar disorder. Methods: We studied 17 patients with bipolar disorder and 17 age- and gender-matched healthy subjects on a 1.5-T nuclear magnetic resonance (NMR) machine. With ¹H-MRSI we measured ratios of areas under the metabolite peaks of the proton spectra (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions. Results: Patients showed significant reductions of NAA/CRE bilaterally in the hippocampus. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. Conclusions: This study shows that patients with bipolar disorder have a regional reduction of NAA relative signals, suggesting neuronal damage or malfunction of the hippocampus. As suggested by other studies, neuronal pathology in the hippocampus may be involved in the pathophysiology of bipolar disorder and in susceptibility to psychosis.