Measuring mania metabolites: a longitudinal proton spectroscopy study of hypomania

Using single-voxel proton spectroscopy we aimed to investigate changes in metabolite levels in key brain regions during hypomania and euthymia in patients with bipolar disorder (BD).

Nine patients with a diagnosis of BD and nine age, sex, education, and handedness-matched comparison subjects underwent magnetic resonance proton spectroscopy (H(1)-MRS) using a 1.5 T magnet. Patients were assessed whilst hypomanic and euthymic. Metabolite (N-acetyl asparTate, NAA; myo-inositol, mI; choline, Cho) levels in the basal ganglia (BG), anterior cingulate cortex (AC), and frontal cortex (FC) were compared both between groups and within the patient group.

Multivariate analysis revealed significant complex relationships between metabolite levels and brain regions with significant differences observed both between bipolar patients (hypomanic and euthymic) and controls, and across the two mood states. Hypomanic patients had lower mean metabolite levels when averaged across the AC and FC regions, compared with the controls. They also had a smaller difference in mean metabolite levels between the BG and FC than the control group. Euthymic patients were also found to have a smaller difference in the level of NAA between the BG and AC than the control group.

This exploratory study of BD demonstrates significant differences in metabolite levels that vary both with respect to brain region and mood state. Not withstanding the confounding effects of medication and the limitation of small sample size the findings are important as they demonstrate that a longitudinal approach is a useful design especially in the context of a long-term phasic illness.