Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression
Open accessAbstract
Ketamine produces rapid antidepressant effects in treatment-resistant depression (TRD), but the magnitude of response varies considerably between individual patients. Brain-derived neurotrophic factor (BDNF) has been investigated as a biomarker of treatment response in depression and has been implicated in the mechanism of action of ketamine. We evaluated plasma BDNF and associations with symptoms in 22 patients with TRD enrolled in a randomized controlled trial of ketamine compared to an anaesthetic control (midazolam). Ketamine significantly increased plasma BDNF levels in responders compared to non-responders 240 min post-infusion, and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were negatively correlated with BDNF (r=-0.701, p = 0.008). Plasma BDNF levels at 240 min post-infusion were highly negatively associated with MADRS scores at 240 min (r = -0.897, p=.002), 24 h (r = -0.791, p = 0.038), 48 h (r = -0.944, p = 0.001) and 72 h (r = -0.977, p = 0.010). No associations with BDNF were found for patients receiving midazolam. These data support plasma BDNF as a peripheral biomarker relevant to ketamine antidepressant response.
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Low dose ketamine infusion increases the serum concentration of BDNF especially in responders to treatment.
“Low dose ketamine infusion has also been found to increase the serum concentration of BDNF especially in responders to treatment (Haile et al., 2014) suggesting plasma BDNF may be a potential biomarker for the antidepressant effects of ketamine (Haile et al., 2014).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Haile et al., 2014
The Methods describe a single 0.5 mg/kg ketamine infusion, and the Discussion reports increased BDNF at 240 minutes in responders compared with non-responders, supporting its potential relevance as a response biomarker. However, the paper measured plasma BDNF, not serum BDNF; the Discussion explicitly says the authors chose plasma rather than serum. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPlasma BDNF may be a potential biomarker for the antidepressant effects of ketamine.
“Low dose ketamine infusion has also been found to increase the serum concentration of BDNF especially in responders to treatment (Haile et al., 2014) suggesting plasma BDNF may be a potential biomarker for the antidepressant effects of ketamine (Haile et al., 2014).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Haile et al., 2014
In 22 patients with TRD randomized to IV ketamine 0.5 mg/kg or IV midazolam 0.045 mg/kg, ketamine significantly increased plasma BDNF levels in responders compared to non-responders at 240 min after infusion.
“one study examined plasma BDNF levels in 22 patients with TRD who were randomized to receive either intravenous ketamine at 0.5 mg/kg or intravenous midazolam at 0.045 mg/kg. The study found that ketamine significantly increased plasma BDNF levels in responders compared to non-responders, with measurements taken 240 min after infusion [94].”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [94]
Ketamine responders with treatment-resistant depression demonstrated rapid elevations in plasma BDNF levels, although another study did not support this finding.
“Ketamine responders with TRD demonstrated rapid elevations in plasma BDNF levels112,113; however, another study did not support this finding.114”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [112]
Higher levels of BDNF were correlated with lower severity of depressive symptoms on rating scales.
“In the aforementioned investigations, higher levels of BDNF were correlated with lower severity of depressive symptoms on rating scales.”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [112]
BDNF is a well-known potential marker of antidepressant response, and the magnitude of increase has been seen to predict acute mood response to ketamine.
“BDNF is a well-known potential marker of antidepressant response,136 and the magnitude of increase has been seen to predict acute mood response to ketamine.112”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [112]
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- Authors
- Haile, C. N., Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Foulkes, A., Iqbal, S., Mahoney, J. J., De La Garza, R., Charney, D. S., Newton, T. F., & Mathew, S. J.
- Affiliations
- Michael E. DeBakey VA Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- Baylor College of Medicine (US)
- Corresponding author
- Mathew, S. J.
- ORCID
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10-08
- Volume
- 17
- Issue
- 02
- Pages
- 331-336
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC3992942
- OpenAlex
- W2167565363
- Cited by
- 253
- References
- 22
- Citations by year
- 2026: 6 · 2025: 19 · 2024: 17 · 2023: 16 · 2022: 30 · 2021: 23 · 2020: 26 · 2019: 20 · 2018: 22 · 2017: 13 · 2016: 24 · 2015: 21 · 2014: 15 · 2012: 1
- FWCI
- 14.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (UL1TR000067)
- National Institute of Mental Health (R01MH081870, K23MH094707)
- National Institute on Drug Abuse (R25DA028976)
- National Center for Advancing Translational Sciences
- 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
- brain-derived neurotrophic factor, plasma BDNF, ketamine, treatment-resistant depression, antidepressant response, biomarkers, midazolam, rapid-acting antidepressants, depression severity
- MeSH terms
- Adult, Aged, Aged, 80 and over, Double-Blind Method, Female, Humans, Ketamine, Male, Midazolam, Middle Aged, Biomarkers, Treatment Outcome, Brain-Derived Neurotrophic Factor, Young Adult, Depressive Disorder, Treatment-Resistant
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