Lower N-acetyl-aspartate levels in prefrontal cortices in pediatric bipolar disorder: A 1H magnetic resonance spectroscopy study

Sheila C. Caetano, Rene L. Olvera, John P. Hatch, Marsal Sanches, Hua Hsuan Chen, Mark Nicoletti, Jeffrey A. Stanley, Manoela Fonseca, Kristina Hunter, Beny Lafer, Steven R. Pliszka, Jair C. Soares

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Objective The few studies applying single-voxel1H 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. Method 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 vivo1H 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 MannWhitney 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.

Original languageEnglish (US)
Pages (from-to)85-94
Number of pages10
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number1
StatePublished - Jan 2011


  • N-acetyl aspartate
  • bipolar disorder
  • magnetic resonance spectroscopy
  • prefrontal cortex

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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