This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (74)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Nutritional and Metabolic Disorders  • Metabolism  • Bipolar Disorder  • Alert me on articles by topic

Stephen R. Dager, MD; Seth D. Friedman, PhD; Aimee Parow, BS; Christina Demopulos, MD; Andrew L. Stoll, MD; In Kyoon Lyoo, MD, PhD; David L. Dunner, MD; Perry F. Renshaw, MD, PhD

Arch Gen Psychiatry. 2004;61:450-458.

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-cm³ 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 -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.

From the Departments of Radiology (Drs Dager and Friedman), Psychiatry and Behavioral Sciences (Drs Dager and Dunner), and Bioengineering (Dr Dager), University of Washington, Seattle; Consolidated Departments of Psychiatry, Harvard Medical School, Boston, Mass (Ms Parow and Drs Demopulos, Stoll, and Renshaw); and Department of Psychiatry, Seoul National University, Seoul, Korea (Dr Lyoo).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Differences in Lymphocyte Electron Transport Gene Expression Levels Between Subjects With Bipolar Disorder and Normal Controls in Response to Glucose Deprivation Stress
Naydenov et al.
Arch Gen Psychiatry 2007;64:555-564.
ABSTRACT | FULL TEXT  

Reduced Prefrontal Glutamate/Glutamine and {gamma}-Aminobutyric Acid Levels in Major Depression Determined Using Proton Magnetic Resonance Spectroscopy
Hasler et al.
Arch Gen Psychiatry 2007;64:193-200.
ABSTRACT | FULL TEXT  

Gray and White Matter Brain Chemistry in Young Children With Autism.
Friedman et al.
Arch Gen Psychiatry 2006;63:786-794.
ABSTRACT | FULL TEXT  

Brain pH Response to Hyperventilation in Panic Disorder: Preliminary Evidence for Altered Acid-Base Regulation
Friedman et al.
Am. J. Psychiatry 2006;163:710-715.
ABSTRACT | FULL TEXT  

Basal Ganglia Shape Alterations in Bipolar Disorder
Hwang et al.
Am. J. Psychiatry 2006;163:276-285.
ABSTRACT | FULL TEXT  

Increased Medial Thalamic Creatine-Phosphocreatine Found by Proton Magnetic Resonance Spectroscopy in Children With Obsessive-Compulsive Disorder Versus Major Depression and Healthy Controls
Mirza et al.
J Child Neurol 2006;21:106-111.
ABSTRACT  

Effects of Type 1 Diabetes on Gray Matter Density as Measured by Voxel-Based Morphometry
Musen et al.
Diabetes 2006;55:326-333.
ABSTRACT | FULL TEXT  

Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis
Iwamoto et al.
Hum Mol Genet 2005;14:241-253.
ABSTRACT | FULL TEXT