• bipolar disorder;
  • brain imaging;
  • dorsolateral prefrontal cortex;
  • magnetic resonance spectroscopy

Objectives:  While the pathophysiology of bipolar disorder (BD) remains to be elucidated, postmortem and neuroimaging studies have suggested that abnormalities in the dorsolateral prefrontal cortex (DLPFC) are implicated. We compared the levels of specific brain chemicals of interest measured with proton magnetic resonance spectroscopy (1H MRS) in medication-free BD subjects and age- and gender-matched healthy controls. We hypothesized that BD subjects would present abnormal cellular metabolism within the DLPFC, as reflected by lower N-acetyl-aspartate (NAA) and creatine + phosphocreatine (Cr + PCr).

Methods:  Thirty-two medication-free BD subjects (33.8 ± 10.2 years) and 32 matched controls (33.8 ± 9.0 years) underwent a short echo-time (TE = 30 ms) 1H MRS. An 8-cm3 single voxel was placed in the left DLPFC, and individual concentrations of NAA, Cr + PCr, choline-containing compounds (GPC + PC), myo-inositol, and glutamate were obtained, using the water signal as an internal reference.

Results:  BD subjects had lower Cr + PCr [F(1,62) = 5.85; p = 0.018; one-way analysis of variance (ANOVA)] and lower GPC + PC [F(1,62) = 5.79; p = 0.019; one-way ANOVA] levels in the left DLPFC. No significant differences were observed for other brain metabolites.

Conclusions:  These findings provide further evidence that the pathophysiology of BD involves impairment in the DLPFC. Our findings can be interpreted as evidence for reduced cellular energy and phospholipid metabolism, consistent with the hypothesis of mitochondrial dysfunction in BD.