Brain-derived neurotrophic factor Val66Met polymorphism and antidepressant efficacy of ketamine in depressed patients
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In patients, Val/Val individuals showed greater response to ketamine therapy 4 hours after treatment, with a 41% reduction in HAM-D score, compared with Met allele carriers, who had a 24% reduction.
“Val/Val patients were more responsive 4 hours post-treatment (41% reduction in HAM-D score) to ketamine therapy relative to Met allele carriers (24% reduction in HAM-D score) (Laje et al., 2012).”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Laje et al., 2012
A small trial found an increased antidepressant response to ketamine in individuals with the val/val than met carriers.
“A small trial investigated ketamine treatment outcomes in patients with major depression carrying either the functional BDNF val66val allele against met carriers found an increased antidepressant response to ketamine in individuals with the val/val than met carriers (Laje et al., 2012) suggesting that alterations in BDNF function can impact ketamine's antidepressant effects.”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Laje et al., 2012
Patients with a Val66Met single-nucleotide polymorphism associated with impairments in BDNF release and mRNA trafficking were found to have reduced responses to ketamine.
“Interestingly, patients with a Val66Met single-nucleotide polymorphism associated with impairments in BDNF release and mRNA trafficking were also found to have reduced responses to ketamine.115,116”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [115]
Data from human studies, including the authors' group, show ketamine's rapid antidepressant effects even in individuals with treatment-resistant depression.
“data from human studies, including our group [103], show ketamine's rapid antidepressant effects even in individuals with treatment-resistant depression”
From Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression (2025) · cites this paper as [105]
An increase in BDNF synthesis is required for the antidepressant actions of ketamine.
“Similar to these findings in mice, Laje et al., (2012) 164 demonstrated that major depressed patients carrying the Met rs6265 allele did not respond to ketamine, further suggesting that increase in BDNF synthesis is required for the antidepressant actions of ketamine.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [164]
Major depressed patients carrying the Met rs6265 allele did not respond to ketamine.
“Similar to these findings in mice, Laje et al., (2012) 164 demonstrated that major depressed patients carrying the Met rs6265 allele did not respond to ketamine, further suggesting that increase in BDNF synthesis is required for the antidepressant actions of ketamine.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [164]
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“…depression carrying either the functional BDNF val66val allele against met carriers found an increased antidepressant response to ketamine in individuals with the val/val than met carriers (Laje et al., 2012) suggesting that alterations in BDNF function can impact ketamine's antidepressant effects.”
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- Authors
- Laje, G., Lally, N., Mathews, D., Brutsche, N., Chemerinski, A., Akula, N., Kelmendi, B., Simen, A., McMahon, F. J., Sanacora, G., & Zarate, C.
- Affiliations
- National Institutes of Health (US)
- University College London (GB)
- Yale University (US)
- Corresponding author
- Zarate, Carlos
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 72
- Issue
- 11
- Pages
- e27-e28
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3786174
- OpenAlex
- W2152644978
- Cited by
- 213
- References
- 15
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 3 · 2023: 16 · 2022: 18 · 2021: 26 · 2020: 18 · 2019: 17 · 2018: 13 · 2017: 16 · 2016: 13 · 2015: 17 · 2014: 20 · 2013: 17 · 2012: 3
- FWCI
- 13.41
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institutes of Health (K99MH085098)
- AstraZeneca
- Bristol-Myers Squibb
- Hoffman La-Roche
- Merck & Co.
- Sunovion Inc
- 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, BDNF Val66Met polymorphism, major depressive disorder, treatment-resistant depression, rapid antidepressant effects, NMDA receptor antagonism, antidepressant efficacy, genetic susceptibility, bipolar depression, mTOR signaling, synaptogenesis, antidepressant side effects, mood stabilizers, lithium, valproic acid, mood stabilizer side effects
- MeSH terms
- Adult, Antidepressive Agents, Depressive Disorder, Double-Blind Method, Female, Humans, Ketamine, Male, Middle Aged, Treatment Outcome, Cross-Over Studies, Brain-Derived Neurotrophic Factor, Polymorphism, Single Nucleotide
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