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

• Published in: The American journal of geriatric psychiatry Vol. 27; no. 8; p. 783
• Main Authors: Mellen, Emily J, Harper, David G, Ravichandran, Caitlin, Jensen, Eric, Silveri, Marisa, Forester, Brent P
• Format: Journal Article
• Language: English
• Published: England 01.08.2019
• Subjects: 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; NAA (N-acetyl aspartate); bipolar depression; lamotrigine; proton magnetic resonance spectroscopy; Geriatric
• ISSN: 1545-7214
• DOI: 10.1016/j.jagp.2019.02.017

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 ( H) 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. 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 H 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. 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. Group differences in NAA suggest evidence for a deficit in cerebral energy metabolism in OABD.