Lamotrigine Therapy and Biomarkers of Cerebral Energy Metabolism in Older Age Bipolar Depression

Am J Geriatr Psychiatry. 2019 Aug;27(8):783-793. doi: 10.1016/j.jagp.2019.02.017. Epub 2019 Mar 6.


Objective: This study compared brain energy metabolism, as measured by cerebral concentrations of glutamate (Glu), glutamine (Gln), and N-acetyl aspartate (NAA), in older age bipolar depression (OABD) to that of psychiatrically healthy comparison subjects using proton (1H) magnetic resonance spectroscopy imaging at 4-Tesla. Metabolite levels were assessed in OABD subjects before and after 8 weeks of lamotrigine therapy with the goal of determining relationships between cerebral energy metabolism, depression symptom severity, and changes in depression symptom response.

Methods: Individuals (n = 21, mean age: 62.0 ± 5.9 years) with bipolar disorder, current episode depressed, and a healthy comparison group (n = 14, mean age: 67.5 ± 8.8 years) were selected. Participants with bipolar disorder, current episode depressed, were treated in open label fashion with lamotrigine monotherapy for 8 weeks. All subjects were scanned with 1H magnetic resonance spectroscopy at 4T at baseline and again after 8 weeks to assess levels of cerebral metabolites in the anterior cingulate cortex and parieto-occipital cortex. Metabolite levels were examined as ratios relative to creatine (Cr). Response to 8 weeks of lamotrigine treatment in the bipolar disorder, current episode depressed group, was assessed as a continuous measure on the Montgomery-Asberg Depression Rating Scale.

Results: NAA/Cr ratio in OABD was significantly lower by 14% (95% confidence interval: [1%, 26%]) than in comparison subjects at baseline. However, there were no associations between NAA/Cr, Glu/Cr, or Gln/Cr and either depression severity or lamotrigine treatment.

Conclusion: Group differences in NAA suggest evidence for a deficit in cerebral energy metabolism in OABD.

Keywords: Geriatric; NAA (N-acetyl aspartate); bipolar depression; lamotrigine; proton magnetic resonance spectroscopy.

Publication types

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

MeSH terms

  • Aged
  • Aging / metabolism*
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / pharmacology*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Biomarkers / metabolism
  • Bipolar Disorder / diagnostic imaging
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / metabolism*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Creatine / metabolism
  • Depression / diagnostic imaging
  • Depression / drug therapy
  • Depression / metabolism
  • Energy Metabolism*
  • Female
  • Follow-Up Studies
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Humans
  • Lamotrigine / administration & dosage
  • Lamotrigine / pharmacology*
  • Male
  • Middle Aged
  • Proton Magnetic Resonance Spectroscopy
  • Severity of Illness Index
  • Treatment Outcome


  • Antipsychotic Agents
  • Biomarkers
  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate
  • Creatine
  • Lamotrigine