Low levels of N-acetyl aspartate in the left dorsolateral prefrontal cortex of pediatric bipolar patients

J Child Adolesc Psychopharmacol. 2007 Aug;17(4):461-73. doi: 10.1089/cap.2007.0102.

Abstract

Background: Increasing evidence suggests abnormalities in the structure, function, and neurochemistry of the frontal cortex in pediatric bipolar (BP) patients. We conducted a single-voxel proton magnetic resonance spectroscopy ((1)H MRS) of the left dorsolateral prefrontal cortex (DLPFC) of pediatric BP patients, expecting lower N-acetyl-aspartate (NAA) levels within that brain region compared to healthy comparison subjects.

Methods: We studied 35 pediatric BP (23 BP type I, 12 BP type II; mean age +/- SD = 13.2 +/- 2.9 years; 18 females) and 36 healthy controls (mean age +/- SD = 13.7 +/- 2.6 years, 17 females). A short echo time, single-voxel (1)H spectroscopy approach point-resolved spectroscopy (PRESS) sequence, measurements of metabolites was performed on a 1.5T Philips MR system.

Results: BP subjects had significantly lower NAA levels in the left DLPFC compared to healthy controls (F = 4.21, df = 1, 68, p = 0.04). There was not a significant difference between groups for phosphocreatine + creatine (PCr+Cr), glycerolphosphocholine + phosphocholine (GPC + PC), myo-inositol (mI), or glutamate. Further analyses revealed a significant reduction of NAA in our early puberty group compared to controls (Mann-Whitney U-test statistic = 52.00, p = 0.014), but not for BP versus controls in other pubertal groups.

Conclusions: BP subjects have lower NAA levels in the left DLPFC compared to healthy subjects, suggesting neuronal dysfunction in this region.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / analysis
  • Aspartic Acid / metabolism
  • Bipolar Disorder / metabolism
  • Bipolar Disorder / physiopathology*
  • Child
  • Creatine / metabolism
  • Female
  • Glycerylphosphorylcholine / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Phosphocreatine / metabolism
  • Phosphorylcholine / metabolism
  • Prefrontal Cortex / chemistry*
  • Prefrontal Cortex / physiopathology*
  • Puberty

Substances

  • Phosphocreatine
  • Phosphorylcholine
  • Aspartic Acid
  • Glycerylphosphorylcholine
  • N-acetylaspartate
  • Creatine