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.