title: Brain metabolic alterations in medication-free patients with bipolar disorder.
abstract: BACKGROUND
  Bipolar disorder (BD) has substantial morbidity and incompletely understood neurobiological underpinnings.
  
  
  OBJECTIVE
  To investigate brain chemistry in medication-free individuals with BD.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Radiology, University of Washington, Seattle 98105, USA. srd@u.washington.edu
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Dager
authors.forename: Seth D
authors.initials: SD
authors.lastname: Friedman
authors.forename: Aimee
authors.initials: A
authors.lastname: Parow
authors.forename: Christina
authors.initials: C
authors.lastname: Demopulos
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Stoll
authors.forename: In Kyoon
authors.initials: IK
authors.lastname: Lyoo
authors.forename: David L
authors.initials: DL
authors.lastname: Dunner
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000328:Adult; D000553:Ambulatory Care; D001714:Bipolar Disorder / Q000175:diagnosis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D003401:Creatine / Q000378:metabolism; D017352:Echo-Planar Imaging; D005260:Female; D006019:Glycolysis; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D007773:Lactates / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011569:Psychiatric Status Rating Scales; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D007773:Lactates; D005680:gamma-Aminobutyric Acid; D003401:Creatine