Hippocampal volume and the rapid antidepressant effect of ketamine
Open accessAbstract
Accumulating evidence underscores the utility of ketamine in treating severely treatment-resistant depressed patients. We investigated the relationship between the rapid antidepressant effects of ketamine and hippocampal volume, a biomarker of antidepressant treatment outcome. We gave 16 medication-free, major depressive disorder (MDD) patients a single, sub-anesthetic dose infusion of ketamine (0.5 mg/kg, over 40 min). We assessed depression severity pre-treatment, and at 24 h post-treatment, with the Montgomery-Åsberg Depression Rating Scale (MADRS). Prior to treatment, patients underwent magnetic resonance imaging (MRI) to estimate their hippocampal volume: We obtained viable MRI data in 13 patients. Delta MADRS (post- minus pre-treatment) was significantly correlated with the pre-treatment volumes of the left hippocampus ( r = 0.66; p = 0.01), but not the right hippocampus ( r = 0.49; p = 0.09). The correlation between delta MADRS and the left hippocampus remained high ( r > 0.6; p = 0.13), after controlling for several demographic and clinical variables, although the p value increased due to the reduced degree of freedom ( df = 5). Ketamine exerts enhanced antidepressant effects in patients with a relatively smaller hippocampus, a patient population that has been repeatedly shown to be refractory to traditional antidepressants.
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A single infusion of low-dose ketamine (0.5 mg/kg) increased hippocampal volume in a small group of unmedicated MDD patients.
“A single infusion of low-dose ketamine (0.5 mg/kg) also increased hippocampal volume (often a proxy for increased BDNF) in a small group of unmedicated MDD patients as well.159”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [159]
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Self-citation
- Authors
- Abdallah, C. G., Salas, R., Jackowski, A., Baldwin, P., Sato, J. R., & Mathew, S. J.
- Affiliations
- Yale University (US)
- Baylor College of Medicine (US)
- Universidade Federal de São Paulo (BR)
- Universidade Federal do ABC (BR)
- Michael E. DeBakey VA Medical Center (US)
- Corresponding author
- Abdallah, Chadi G
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2014-08-13
- Volume
- 29
- Issue
- 5
- Pages
- 591-595
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- PMC
- PMC4852551
- OpenAlex
- W1987349975
- Cited by
- 78
- References
- 26
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 10 · 2022: 10 · 2021: 7 · 2020: 15 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 7 · 2015: 5
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- Funders
- National Institutes of Health (5k23mh101498-05)
- National Institute of Mental Health (K23MH-101498(, R01MH081870)
- Topics
- Health Sciences › Medicine › Pharmacology › 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, hippocampal volume, major depressive disorder, treatment-resistant depression, rapid antidepressant effects, left hippocampus, depression severity
- MeSH terms
- Adult, Antidepressive Agents, Major Depressive Disorder, Double-Blind Method, Female, Hippocampus, Humans, Ketamine, Magnetic Resonance Imaging, Male, Middle Aged, Predictive Value of Tests, Psychiatric Status Rating Scales, Biomarkers, Treatment Outcome, Depressive Disorder, Treatment-Resistant
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