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J Psychopharmacol. 2015 May;29(5):596-607. doi: 10.1177/0269881114568041. Epub 2015 Feb 17.

Neural correlates of change in major depressive disorder anhedonia following open-label ketamine.

Author information

1
Experimental Therapeutics and Pathophysiology Branch, National Institutes of Health/National Institute of Mental Health, Bethesda, MD, USA Institute of Cognitive Neuroscience, University College London, London, UK lallynm@mail.nih.gov.
2
Experimental Therapeutics and Pathophysiology Branch, National Institutes of Health/National Institute of Mental Health, Bethesda, MD, USA.
3
Institute of Cognitive Neuroscience, University College London, London, UK.

Abstract

Anhedonia is a cardinal symptom of major depression and is often refractory to standard treatment, yet no approved medication for this specific symptom exists. In this exploratory re-analysis, we assessed whether administration of rapid-acting antidepressant ketamine was associated specifically with reduced anhedonia in medication-free treatment-refractory patients with major depressive disorder in an open-label investigation. Additionally, participants received either oral riluzole or placebo daily beginning 4 hours post-infusion. A subgroup of patients underwent fluorodeoxyglucose positron emission tomography scans at baseline (1-3 days pre-infusion) and 2 hours post-ketamine infusion. Anhedonia rapidly decreased following a single ketamine infusion; this was sustained for up to three days, but was not altered by riluzole. Reduced anhedonia correlated with increased glucose metabolism in the hippocampus and dorsal anterior cingulate cortex (dACC) and decreased metabolism in the inferior frontal gyrus and orbitofrontal cortex (OFC). The tentative relationship between change in anhedonia and glucose metabolism remained significant in dACC and OFC, and at trend level in the hippocampus, a result not anticipated, when controlling for change in total depression score. Results, however, remain tenuous due to the lack of a placebo control for ketamine. In addition to alleviating overall depressive symptoms, ketamine could possess anti-anhedonic potential in major depressive disorder, which speculatively, may be mediated by alterations in metabolic activity in the hippocampus, dACC and OFC.

KEYWORDS:

18FDG-PET; Anti-anhedonic; NMDA; depression; dorsal anterior cingulate cortex; glutamate; hippocampus; orbitofrontal cortex; reward; riluzole; subiculum

PMID:
25691504
PMCID:
PMC5116382
DOI:
10.1177/0269881114568041
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Declaration of Conflicting Interests The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A patent application for the use of ketamine in depression has been submitted listing Dr Carlos A Zarate among the inventors; he has assigned his rights on the patent to the U.S. government, but will share a percentage of any royalties that may be received by the government. All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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