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

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 (¹H 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 ¹H 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 (ml), 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.