Cited by 224Treatment of Major DepressionElectroconvulsive Therapy StudiesTryptophan and brain disorders

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

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Lally, Níall, Nugent, Allison C, Luckenbaugh, David A, Niciu, Mark J, Roiser, Jonathan P, Zarate, Carlos A·2015·Journal of Psychopharmacology

DOI 10.1177/0269881114568041PMC PMC5116382

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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.

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Authors: Lally, N., Nugent, A. C., Luckenbaugh, D. A., Niciu, M. J., Roiser, J. P., & Zarate, C. A.
Affiliations: National Institutes of Health (US)
University College London (GB)
Corresponding author: Lally, Níall
ORCID: Lally, Níall
Nugent, Allison C
Niciu, Mark J
Roiser, Jonathan P
Zarate, Carlos A
Venue: Journal of Psychopharmacology
Publisher: SAGE Publications
Published: 2015-02-17
Volume: 29
Issue: 5
Pages: 596-607
ISSN: 0269-8811 (ISSN-L)
1461-7285
DOI: 10.1177/0269881114568041
PMC: PMC5116382
OpenAlex: W2113067674
Cited by: 224
References: 70
Citations by year: 2026: 6 · 2025: 13 · 2024: 32 · 2023: 20 · 2022: 33 · 2021: 27 · 2020: 18 · 2019: 22 · 2018: 15 · 2017: 12 · 2016: 19 · 2015: 7
FWCI: 12.63
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: National Institutes of Health
U.S. Public Health Service (04-M-0222)
National Institute of Mental Health (ZIAMH002857)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: ketamine, anhedonia, major depressive disorder, treatment-resistant depression, rapid-acting antidepressants, riluzole, glucose metabolism, hippocampus, dorsal anterior cingulate cortex, orbitofrontal cortex, inferior frontal gyrus, neural correlates, FDG-PET
MeSH terms: Adult, Antidepressive Agents, Major Depressive Disorder, Double-Blind Method, Female, Gyrus Cinguli, Hippocampus, Humans, Ketamine, Male, Middle Aged, Radionuclide Imaging, Treatment Outcome, Anhedonia, Depressive Disorder, Treatment-Resistant

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

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