Ketamine-induced changes in plasma brain-derived neurotrophic factor (BDNF) levels are associated with the resting-state functional connectivity of the prefrontal cortex
Abstract
OBJECTIVES: Synaptic plasticity and brain-derived neurotrophic factor (BDNF) signalling are proposed to play key roles in antidepressant drug action. Ketamine, an N-methyl-D-aspartate receptor antagonist and putative antidepressant, may increase synaptic plasticity in prefrontal cortex through higher expression of BDNF. Furthermore, ketamine was shown to change resting-state functional connectivity (RSFC) of dorsomedial prefrontal cortex (dmPFC). METHODS: In a randomised, placebo-controlled study, we investigated acutely (100 min) and at 24 h following subanesthetic ketamine infusion which dmPFC seeded RSFC changes are most strongly associated with plasma BDNF level changes in 53 healthy participants (21 females, age: 24.4 ± 2.9 years) using 7 T-fMRI. RESULTS: We observed higher relative levels of BDNF 2 h and 24 h after ketamine compared to placebo. Whole-brain regression revealed that the change in BDNF after 24 h was associated with RSFC decreases from dmPFC to posterior cingulate cortex and ventromedial PFC at 24 h and exploratively also at the 100 min measurement point. Follow-up analyses revealed that RSFC reductions following ketamine were restricted to subjects showing increased BDNF levels at 24 h. CONCLUSIONS: Our findings indicate BDNF level dynamics following ketamine are related to acute and 24 h RSFC changes. Particularly when BDNF increases are observed after ketamine infusion, a disconnection from dmPFC after 24 h is seen and may reflect synaptic plasticity effects.
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The antidepressant effects of ketamine may be related to enhanced synaptic plasticity, reflected in both BDNF levels and RSFC changes.
“suggesting that the antidepressant effects of ketamine may be related to enhanced synaptic plasticity, reflected in both BDNF levels and RSFC changes [96].”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [96]
RSFC changes were more pronounced in participants who showed an increase in BDNF levels after ketamine.
“The RSFC changes were more pronounced in participants who showed an increase in BDNF levels after ketamine”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [96]
In 53 healthy participants, ketamine 0.5 mg/kg continuous 40 min infusion resulted in significant increases in plasma BDNF levels at 2 h and 24 h post-infusion.
“The study found that ketamine administration resulted in significant increases in plasma BDNF levels at both 2 h and 24 h post-infusion.”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [96]
In the same study, BDNF changes were associated with decreased RSFC between dmPFC and PCC/vmPFC.
“These BDNF changes were associated with decreased RSFC between the dorsomedial prefrontal cortex (dmPFC) and regions such as the posterior cingulate cortex (PCC) and ventromedial prefrontal cortex (vmPFC).”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [96]
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- Authors
- Woelfer, M., Li, M., Colic, L., Liebe, T., Di, X., Biswal, B., Murrough, J., Lessmann, V., Brigadski, T., & Walter, M.
- Affiliations
- New Jersey Institute of Technology (US)
- University of Tübingen (DE)
- Clinical Affective Neuroimaging Laboratory (CANLAB), Magdeburg, Germany
- Icahn School of Medicine at Mount Sinai (US)
- Center for Behavioral Brain Sciences (DE)
- University of Applied Sciences Kaiserslautern (DE)
- Corresponding author
- Walter, Martin
- ORCID
- Venue
- The World Journal of Biological Psychiatry
- Publisher
- Informa UK Limited
- Published
- 2019-11-04
- Volume
- 21
- Issue
- 9
- Pages
- 696-710
- ISSN
- 1562-2975 (ISSN-L)
- 1814-1412
- OpenAlex
- W2987503628
- Cited by
- 64
- References
- 18
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 11 · 2023: 8 · 2022: 10 · 2021: 15 · 2020: 6
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The World Journal of Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre for Behavioural and Brain Sciences (NN05)
- Medical Faculty of the Otto-von-Guericke-University Magdeburg (779, 2013–2016, 779 B06)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- ketamine, brain-derived neurotrophic factor, resting-state functional connectivity, dorsomedial prefrontal cortex, synaptic plasticity, antidepressant mechanism, plasma BDNF levels, posterior cingulate cortex, ventromedial prefrontal cortex, NMDA receptor antagonists, 7T MRI
- MeSH terms
- Adult, Antidepressive Agents, Female, Humans, Ketamine, Male, Plasma, Prefrontal Cortex, Brain-Derived Neurotrophic Factor, Young Adult
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