Objectives: Proton magnetic resonance spectroscopy (MRS) provides insight into neurochemical processes. Imaging and postmortem studies have implicated abnormalities of structure and function within the frontal lobe. Patients with bipolar disorder having a manic or mixed episode were hypothesized to demonstrate metabolic abnormalities within the frontal lobe.

Methods: Seventeen patients with bipolar disorder type I (ages 16–35 years, mean 22 ± 7.3 years) hospitalized for a manic (n = 9) or mixed (n = 8) episode and 21 healthy subjects (ages 16–35 years, mean 21.7 ± 5.2 years) were evaluated with proton MRS. The gray matter medially and white matter laterally within the frontal lobe were sampled. Metabolite concentrations were calculated for each voxel, corrected for cerebral spinal fluid (CSF) contributions to the voxel, and compared between study populations.

Results: Patients demonstrated with multivariate analyses of variance (MANOVA) a significant overall difference in gray matter metabolite concentrations compared with healthy subjects. The largest effect sizes for group differences were found with reductions of N‐acetyl aspartate (NAA) and Choline (Cho) concentrations (f = 0.41 and 0.37, respectively). A significant group difference with MANOVA in white matter metabolite concentrations was also observed with the largest effect size at f = 0.44 for elevation of the composite amino acid (AA) concentration.

Conclusions: A reduction of NAA within the gray matter of patients suggests neuronal dysfunction. Altered phospholipid metabolism suggestive of a trend toward decreased volume is implicated with a reduction of Cho concentrations. Within white matter, composite concentrations of AAs were elevated in patients indicating altered neurotransmission.