title: Lower N-acetyl-aspartate levels in prefrontal cortices in pediatric bipolar disorder: a ¹H magnetic resonance spectroscopy study.
abstract: OBJECTIVE
  The few studies applying single-voxel ¹H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low N-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol / phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study was to evaluate NAA, glycerophosphocholine plus phosphocholine (GPC+PC) and PCr+Cr in various frontal cortical areas in children and adolescents with BD. We hypothesized that NAA levels within the prefrontal cortex are lower in BD patients than in healthy controls, indicating neurodevelopmental alterations in the former.
  
  
  METHODS
  We studied 43 pediatric patients with DSM-IV BD (19 female, mean age 13.2 ± 2.9 years) and 38 healthy controls (19 female, mean age 13.9 ± 2.7 years). We conducted multivoxel in vivo ¹H spectroscopy measurements at 1.5 Tesla using a long echo time of 272 ms to obtain bilateral metabolite levels from the medial prefrontal cortex (MPFC), DLPFC (white and gray matter), cingulate (anterior and posterior), and occipital lobes. We used the nonparametric Mann-Whitney U test to compare neurochemical levels between groups.
  
  
  RESULTS
  In pediatric BD patients, NAA and GPC+PC levels in the bilateral MPFC, and PCr+Cr levels in the left MPFC were lower than those seen in the controls. In the left DLPFC white matter, levels of NAA and PCr+Cr were also lower in BD patients than in controls.
  
  
  CONCLUSIONS
  Lower NAA and PCr+Cr levels in the PFC of children and adolescents with BD may be indicative of abnormal dendritic arborization and neuropil, suggesting neurodevelopmental abnormalities.
authors.affiliation: University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Caetano
authors.forename: Rene L
authors.initials: RL
authors.lastname: Olvera
authors.forename: John P
authors.initials: JP
authors.lastname: Hatch
authors.forename: Marsal
authors.initials: M
authors.lastname: Sanches
authors.forename: Hua Hsuan
authors.initials: HH
authors.lastname: Chen
authors.forename: Mark
authors.initials: M
authors.lastname: Nicoletti
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Stanley
authors.forename: Manoela
authors.initials: M
authors.lastname: Fonseca
authors.forename: Kristina
authors.initials: K
authors.lastname: Hunter
authors.forename: Beny
authors.initials: B
authors.lastname: Lafer
authors.forename: Steven R
authors.initials: SR
authors.lastname: Pliszka
authors.forename: Jair C
authors.initials: JC
authors.lastname: Soares
mesh_terms: D000293:Adolescent; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D001714:Bipolar Disorder / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry; D002648:Child; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005997:Glycerylphosphorylcholine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010725:Phosphocreatine / Q000737:chemistry / Q000378:metabolism; D010767:Phosphorylcholine / Q000737:chemistry / Q000378:metabolism; D017397:Prefrontal Cortex / Q000737:chemistry / Q000254:growth & development*; D011522:Protons
chemical_list: D011522:Protons; D010725:Phosphocreatine; D010767:Phosphorylcholine; D001224:Aspartic Acid; D007294:Inositol; D005997:Glycerylphosphorylcholine; C000179:N-acetylaspartate