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

• Published in: The American journal of geriatric psychiatry 2019-08, Vol.27 (8), p.783-793
• Main Authors: Mellen, Emily J., Harper, David G., Ravichandran, Caitlin, Jensen, Eric, Silveri, Marisa, Forester, Brent P.
• Format: Article
• Language: English
• Subjects: Aged; Aging - metabolism; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - pharmacology; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Biomarkers; Biomarkers - metabolism; bipolar depression; Bipolar disorder; 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; Drug therapy; Energy Metabolism; Female; Follow-Up Studies; Geriatric; Geriatrics; Glutamic Acid - metabolism; Glutamine - metabolism; Humans; lamotrigine; Lamotrigine - administration & dosage; Lamotrigine - pharmacology; Male; Mental depression; Metabolism; Middle Aged; NAA (N-acetyl aspartate); Older people; Proton Magnetic Resonance Spectroscopy; Severity of Illness Index; Treatment Outcome
• ISSN: 1064-7481; 1545-7214
• DOI: 10.1016/j.jagp.2019.02.017

•What is the primary question addressed by this study? What is the evidence for alterations in cerebral energy metabolism in older adults with bipolar depression?•What is the main finding of this study? Cerebral NAA (N-acetyl aspartate), as measured by proton magnetic resonance spectroscopy (MRS), is significantly in decreased in older adults with bipolar depression (OABD).•What is the meaning of the finding? Reductions in NAA provide support to the hypothesis that mitochondrial dysfunction may be a neurobiological mechanism associated with bipolar depression in older adults. 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. 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. 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.