Journal article
Neural correlates of change in major depressive disorder anhedonia following open-label ketamine
Journal of psychopharmacology (Oxford), Vol.29(5), pp.596-607
05/2015
DOI: 10.1177/0269881114568041
PMCID: PMC5116382
PMID: 25691504
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.
Details
- Title: Subtitle
- Neural correlates of change in major depressive disorder anhedonia following open-label ketamine
- Creators
- Níall Lally - 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.govAllison C Nugent - Experimental Therapeutics and Pathophysiology Branch, National Institutes of Health/National Institute of Mental Health, Bethesda, MD, USADavid A Luckenbaugh - Experimental Therapeutics and Pathophysiology Branch, National Institutes of Health/National Institute of Mental Health, Bethesda, MD, USAMark J Niciu - Experimental Therapeutics and Pathophysiology Branch, National Institutes of Health/National Institute of Mental Health, Bethesda, MD, USAJonathan P Roiser - Institute of Cognitive Neuroscience, University College London, London, UKCarlos A Zarate Jr - Experimental Therapeutics and Pathophysiology Branch, National Institutes of Health/National Institute of Mental Health, Bethesda, MD, USA
- Resource Type
- Journal article
- Publication Details
- Journal of psychopharmacology (Oxford), Vol.29(5), pp.596-607
- DOI
- 10.1177/0269881114568041
- PMID
- 25691504
- PMCID
- PMC5116382
- NLM abbreviation
- J Psychopharmacol
- ISSN
- 0269-8811
- eISSN
- 1461-7285
- Publisher
- United States
- Grant note
- ZIA MH002857-12 / Intramural NIH HHS 04-M-0222 / PHS HHS Intramural NIH HHS
- Language
- English
- Date published
- 05/2015
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003462302771
Metrics
16 Record Views