title: N-acetylaspartate normalization in bipolar depression after lamotrigine treatment.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Croarkin
authors.affiliation: Department of Radiology, Psychiatry, and Biomedical Engineering, Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: M Albert
authors.initials: MA
authors.lastname: Thomas
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Port
authors.affiliation: University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Baruth
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Osama A
authors.initials: OA
authors.lastname: Abulseoud
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
mesh_terms: D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000188:drug therapy*; D001921:Brain / Q000187:drug effects; D004151:Dipeptides; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects; D006801:Humans; D000077213:Lamotrigine; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D004151:Dipeptides; D014227:Triazines; C027172:isospaglumic acid; D001224:Aspartic Acid; C000179:N-acetylaspartate; D000077213:Lamotrigine
keywords: N-acetylaspartate; bipolar depression; bipolar disorder; lamotrigine; neuroprotection; two-dimensional proton magnetic resonance spectroscopy