title: A proton magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in acute mania.
abstract: BACKGROUND
  Several neurochemical abnormalities have been reported in bipolar disorder (BD), but the exact mechanisms that underlie its pathophysiology remain to be elucidated. Proton magnetic resonance spectroscopy (1HMRS) allows in vivo measurements of certain neurometabolites in the human brain. 1HMRS was used to investigate the dorsolateral prefrontal cortex (DLPFC) in bipolar subjects during a manic or mixed phase. N-acetyl-L-aspartate (NAA), choline-containing molecules (Cho), creatine plus phosphocreatine (Cr) and myoinositol (Ino) were measured.
  
  
  METHODS
  Ten bipolar patients (nine manic, one mixed), diagnosed by a semi-structured clinical interview (SCID), and ten age- and gender-matched healthy volunteers were studied. Absolute neurometabolites levels were measured from two 8 cm3 voxels placed in left and right DLPFC using a short TE 1HMRS method at 1.5 T. T1- and T2-weighted anatomical magnetic resonance imaging was performed to exclude any neuroanatomical abnormality.
  
  
  RESULTS
  No significant differences were found for NAA, Cho, Cr, Ino, NAA/Cr, Cho/Cr or Ino/Cr between patients and controls. Manic/mixed patients had significantly higher left-to-right myoinositol ratios in DLPFC (p = 0.044).
  
  
  CONCLUSIONS
  Increased left-to-right myoinositol ratios in the DLPFC in bipolar patients during acute mania may represent a dysfunction in the phosphoinositide-signaling pathway. Longitudinal studies with larger samples of unmedicated patients assessing pre- and post-treatment times will be required for further clarification of the time course of these abnormalities and the relationship with treatment effects.
authors.affiliation: Laboratório de Psiquiatria Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brasil. benicio.frey@terra.com.br
authors.forename: Benício N
authors.initials: BN
authors.lastname: Frey
authors.forename: Marcelo
authors.initials: M
authors.lastname: Folgierini
authors.forename: Mark
authors.initials: M
authors.lastname: Nicoletti
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Stanley
authors.forename: Jair C
authors.initials: JC
authors.lastname: Soares
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
mesh_terms: D000208:Acute Disease; D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010725:Phosphocreatine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology*
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D010725:Phosphocreatine; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D002794:Choline