title: Abnormal cellular energy and phospholipid metabolism in the left dorsolateral prefrontal cortex of medication-free individuals with bipolar disorder: an in vivo 1H MRS study.
abstract: OBJECTIVE
  While the pathophysiology of bipolar disorder (BD) remains to be elucidated, postmortem and neuroimaging studies have suggested that abnormalities in the dorsolateral prefrontal cortex (DLPFC) are implicated. We compared the levels of specific brain chemicals of interest measured with proton magnetic resonance spectroscopy ((1)H MRS) in medication-free BD subjects and age- and gender-matched healthy controls. We hypothesized that BD subjects would present abnormal cellular metabolism within the DLPFC, as reflected by lower N-acetyl-aspartate (NAA) and creatine + phosphocreatine (Cr + PCr).
  
  
  METHODS
  Thirty-two medication-free BD subjects (33.8 +/- 10.2 years) and 32 matched controls (33.8 +/- 9.0 years) underwent a short echo-time (TE = 30 ms) (1)H MRS. An 8-cm(3) single voxel was placed in the left DLPFC, and individual concentrations of NAA, Cr + PCr, choline-containing compounds (GPC + PC), myo-inositol, and glutamate were obtained, using the water signal as an internal reference.
  
  
  RESULTS
  BD subjects had lower Cr + PCr [F((1,62)) = 5.85; p = 0.018; one-way analysis of variance (ANOVA)] and lower GPC + PC [F((1,62)) = 5.79; p = 0.019; one-way ANOVA] levels in the left DLPFC. No significant differences were observed for other brain metabolites.
  
  
  CONCLUSIONS
  These findings provide further evidence that the pathophysiology of BD involves impairment in the DLPFC. Our findings can be interpreted as evidence for reduced cellular energy and phospholipid metabolism, consistent with the hypothesis of mitochondrial dysfunction in BD.
authors.affiliation: MOOD-CNS Program, Division of Mood and Anxiety Disorders, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, TX 78229, USA. benicio.frey@gmail.com
authors.forename: Benício N
authors.initials: BN
authors.lastname: Frey
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Stanley
authors.forename: Fabiano G
authors.initials: FG
authors.lastname: Nery
authors.forename: E Serap
authors.initials: ES
authors.lastname: Monkul
authors.forename: Mark A
authors.initials: MA
authors.lastname: Nicoletti
authors.forename: Hua-Hsuan
authors.initials: HH
authors.lastname: Chen
authors.forename: John P
authors.initials: JP
authors.lastname: Hatch
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Caetano
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Ortiz
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: Jair C
authors.initials: JC
authors.lastname: Soares
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives; D001714:Bipolar Disorder / Q000473:pathology*; D016022:Case-Control Studies; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010725:Phosphocreatine / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology*; D011522:Protons; D012720:Severity of Illness Index
chemical_list: D010743:Phospholipids; D011522:Protons; D010725:Phosphocreatine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine