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Arch Gen Psychiatry. 2004 May;61(5):450-8.

Brain metabolic alterations in medication-free patients with bipolar disorder.

Author information

1
Department of Radiology, University of Washington, Seattle 98105, USA. srd@u.washington.edu

Abstract

BACKGROUND:

Bipolar disorder (BD) has substantial morbidity and incompletely understood neurobiological underpinnings.

OBJECTIVE:

To investigate brain chemistry in medication-free individuals with BD.

DESIGN:

Two-dimensional proton echo-planar spectroscopic imaging (PEPSI) (32 x 32, 1-cm(3) voxel matrix) acquired axially through the cingulate gyrus was used to quantify regional brain chemistry.

SETTING:

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.

PARTICIPANTS:

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 gamma-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 evaluated.

RESULTS:

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.

CONCLUSIONS:

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 treatment interventions.

PMID:
15123489
DOI:
10.1001/archpsyc.61.5.450
[Indexed for MEDLINE]
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