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Brain Metabolic Alterations in Medication-Free Patients With BipolarDisorder
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.
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“The severity of a depressive episode has been inversely linked to white matter creatine and PCr concentrations within the brain suggesting that there is a relationship between brain creatine metabolism and depression [79].”
From Creatine supplementation in women's health: a lifespan perspective (2021) · cites this paper as [79]
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Metadata
- Authors
- Dager, S. R., Friedman, S. D., Parow, A., Demopulos, C., Stoll, A. L., Lyoo, I. K., Dunner, D. L., & Renshaw, P. F.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2004-05-01
- Volume
- 61
- Issue
- 5
- Pages
- 450
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2117217305
- Cited by
- 453
- References
- 10
- FWCI
- 15.05
- Type
- journal article
- Language
- en
- Open access
- closed
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