N-acetylaspartate normalization in bipolar depression after lamotrigine treatment

Bipolar Disord. 2015 Jun;17(4):450-7. doi: 10.1111/bdi.12285. Epub 2014 Dec 12.

Abstract

Objectives: The aim of the present study was to examine N-acetylaspartate (NAA), a general marker of neuronal viability, and total NAA (tNAA), the combined signal of NAA and N-acetylaspartylglutamate, in bipolar depression before and after lamotrigine treatment. Given that NAA is synthesized through direct acetylation of aspartate by acetyl-coenzyme A-l-aspartate-N-acetyltransferase, we hypothesized that treatment with lamotrigine would be associated with an increase in NAA level.

Methods: Patients with bipolar depression underwent two-dimensional proton magnetic resonance spectroscopy of the anterior cingulate at baseline (n = 15) and after 12 weeks of lamotrigine treatment (n = 10). A group of age-matched healthy controls (n = 9) underwent scanning at baseline for comparison.

Results: At baseline, patients with bipolar depression had significantly lower NAA [mean standard deviation (SD) = 1.13 (0.21); p = 0.02] than controls [mean (SD) = 1.37 (0.27)]. Significant increases in NAA [mean (SD) = 1.39 (0.21); p = 0.01] and tNAA [mean (SD) = 1.61 (0.25); p = 0.02] levels were found after 12 weeks of lamotrigine treatment.

Conclusions: These data suggest an NAA deficit in bipolar depression that is normalized after lamotrigine treatment. Future research is warranted to evaluate whether baseline NAA level is a potential biomarker for identifying lamotrigine response patterns and whether this functional brain change has an associated clinical response.

Keywords: N-acetylaspartate; bipolar depression; bipolar disorder; lamotrigine; neuroprotection; two-dimensional proton magnetic resonance spectroscopy.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Biomarkers / metabolism
  • Bipolar Disorder / drug therapy*
  • Brain / drug effects
  • Dipeptides
  • Female
  • Gyrus Cinguli / drug effects
  • Humans
  • Lamotrigine
  • Magnetic Resonance Spectroscopy* / methods
  • Male
  • Middle Aged
  • Reference Values
  • Triazines / therapeutic use*

Substances

  • Biomarkers
  • Dipeptides
  • Triazines
  • isospaglumic acid
  • Aspartic Acid
  • N-acetylaspartate
  • Lamotrigine