@article{69c3381c76914d31bfc366ad6f788767,
title = "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.",
keywords = "Ketamine, MRI, biological psychiatry, brain-derived neurotrophic factor, prefrontal cortex",
author = "Marie Woelfer and Meng Li and Lejla Colic and Thomas Liebe and Xin Di and Bharat Biswal and James Murrough and Volkmar Lessmann and Tanja Brigadski and Martin Walter",
note = "Funding Information: Dr. Walter performed studies with institutional research support from HEEL and from Janssen Pharmaceutical Research for an IIT on ketamine in patients with major depression unrelated to this investigation. Dr. Walter has not received any personal financial compensation from third parties. In the past 5 years, Dr. Murrough has provided consultation services to Sage Therapeutics, Novartis, Allergan, Fortress Biotech, Janssen Research and Development, Genentech, Medavante-Prophase, and Global Medical Education (GME) and has received research support from Avanir Pharmaceuticals, Inc. The Icahn School of Medicine (employer of Dr. Murrough) is named on a patent and has entered into a licencing agreement and will receive payments related to the use of ketamine if it is approved for the treatment of depression. Dr. Murrough is not named on this patent and will not receive any payments. Other authors declare no conflict of interest. Funding Information: This work was supported by German Research Foundation [SFB 779/A06 for MWa, and DFG Wa 2673/4-1 for MWa], the Centre for Behavioural and Brain Sciences [CBBS NN05 for MWa], and Leibniz Association [Pakt f{\"u}r Forschung und Innovation for MWa]. MWo and TL were supported by scholarship from the Medical Faculty of the Otto-von-Guericke-University Magdeburg and MWo received a scholarship from the German Academic Exchange Service (DAAD). LC was supported by a scholarship from German Research Foundation [SFB 779, 2013–2016]. VL was supported by grants from the German Research Foundation [DFG, SFB 779 B06]. We would like to thank Dr. Claus Tempelmann and Renate Blobel (Department of Neurology) for data acquisition; Dr. Melanie Weigel (Department of Ophthalmology) and Dr. Conrad Friedrich Genz (Department of Cardiology) for clinical screening; Dr. Julia Noack and Linda Frolik Endrulat (Clinical Affective Neuroimaging Laboratory) for trial management. We would like to acknowledge and thank all participants in this study. Publisher Copyright: {\textcopyright} 2019 Informa UK Limited, trading as Taylor & Francis Group.",
year = "2020",
month = oct,
day = "20",
doi = "10.1080/15622975.2019.1679391",
language = "English (US)",
volume = "21",
pages = "696--710",
journal = "World Journal of Biological Psychiatry",
issn = "1562-2975",
publisher = "Informa Healthcare",
number = "9",
}