Bipolar disorder (BD) has substantial morbidity and incompletely understood
To investigate brain chemistry in medication-free individuals with BD.
Two-dimensional proton echo-planar spectroscopic imaging (PEPSI) (32
× 32, 1-cm3 voxel matrix) acquired axially through the cingulate
gyrus was used to quantify regional brain chemistry.
The Center for Anxiety and Depression at the University of Washington
in Seattle and the Bipolar Research Programs at McLean Hospital and the Massachusetts
General Hospital in Boston.
Thirty-two medication-free outpatients with a diagnosis of BD type I
(BDI) or BD type II (BDII), predominantly in a depressed or mixed-mood state,
were compared with 26 age- and sex-matched healthy controls.
Main Outcome Measures
Tissue type (white and gray) and regional analyses were performed to
evaluate distribution of lactate; glutamate, glutamine, and γ-aminobutyric
acid (Glx); creatine and phosphocreatine (Cre); choline-containing compounds
(Cho); N-acetyl aspartate; and myo-inositol. Chemical relationships for diagnosis and mood state were
Patients with BD exhibited elevated gray matter lactate (P = .005) and Glx (P = .007) levels; other
gray and white matter chemical measures were not significantly different between
diagnostic groups. Isolated regional chemical alterations were found. An inverse
correlation between 17-item Hamilton Depression Rating Scale scores and white
matter Cre levels was observed for BD patients.
Gray matter lactate and Glx elevations in medication-free BD patients
suggest a shift in energy redox state from oxidative phosphorylation toward
glycolysis. The possibility of mitochondrial alterations underlying these
findings is discussed and may provide a theoretical framework for future targeted