Contributed equally to this manuscript as senior authors.
Neural correlates of rapid antidepressant response to ketamine in bipolar disorder
Article first published online: 18 SEP 2013
Published 2013. This article is a U.S. Government work and is in the public domain in the USA
Volume 16, Issue 2, pages 119–128, March 2014
How to Cite
Neural correlates of rapid antidepressant response to ketamine in bipolar disorder. Bipolar Disord 2014: 16: 119–128. Published 2013. This article is a U.S. Government work and is in the public domain in the USA., , , , , , , , .
ClinicalTrials.gov Identifier: NCT00088699.
- Issue published online: 5 MAR 2014
- Article first published online: 18 SEP 2013
- Manuscript Accepted: 2 JUL 2013
- Manuscript Received: 19 FEB 2013
- Intramural Research Program
- National Institute of Mental Health
- National Institutes of Health
- bipolar disorder;
- N-methyl d-aspartate (NMDA) antagonist;
- positron emission tomography (PET)
Ketamine, an N-methyl d-aspartate (NMDA) antagonist, has rapid antidepressant effects in depressed subjects with bipolar disorder (BD). Evidence supports a role for the glutamatergic system in the pathophysiology of BD. This double-blind, randomized, cross-over study sought to determine cerebral metabolic correlates of antidepressant response to ketamine.
Twenty-one subjects with BD currently in a depressed state underwent [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging after receiving a placebo infusion as well as after receiving a ketamine infusion. Metabolism was compared between ketamine and placebo infusions, and correlated with clinical response. Regional metabolic rate of glucose (rMRGlu) in regions of interest (ROIs) and Montgomery–Åsberg Depression Rating Scale (MADRS) scores were the main outcome measures.
The study found that change in metabolism between sessions was significantly correlated with percentage change in MADRS scores in the right ventral striatum; subjects who showed the greatest improvement had the largest metabolic increase after ketamine infusion compared to placebo. In a voxel-wise analysis, subjects with BD had significantly lower glucose metabolism in the left hippocampus following the ketamine infusion than following the placebo infusion. In addition, metabolism in the subgenual anterior cingulate cortex (ACC) following the placebo infusion was positively correlated with percentage improvement in MADRS score following the ketamine infusion.
Taken together, the results suggest that higher activity in the subgenual ACC may predict antidepressant response to ketamine. Ketamine administration altered glucose metabolism in areas known to be involved in mood disorders; these alterations may partially underlie ketamine's mechanism of action.