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Philadelphia, January 31, 2019 — A study conducted by researchers from Yale University reveals a complex interaction of two different growth factors in fast-acting and long-lasting antidepressant effects of ketamine. The study, published in Biological psychiatry, reports that actions similar to antidepressants of brain-derived neurotrophic factor (BDNF) require the release of vascular endothelial growth factor (VEGF).
"Surprisingly, the reciprocal relationship has also been observed, indicating that BDNF-VEGF interdependence plays a crucial role in the action of fast-acting antidepressants," said lead author Ronald Duman, PhD.
Ketamine requires the release of BDNF and VEGF to produce its rapid antidepressant effects, but the connection between the two growth factors – which have different functions and act through different mechanisms – was unknown.
Using mice to model depressive behaviors, researchers investigated the interaction of BDNF and VEGF. The administration of BDNF or VEGF in a brain region involved in depression, the medial prefrontal cortex (mPFC), produces fast and lasting antidepressant effects similar to those of ketamine. In the study, Dr. Duman and colleagues found that VEGF withdrawal from mPFC prevented the effects of BDNF-like antidepressant medications in mice. When they performed similar experiments but that they blocked BDNF, the effects of VEGF badogous to those of antidepressants were avoided.
Further badysis using neuronal cultures to examine how both factors depend on each other revealed that BDNF signaling stimulates VEGF release in neurons and requires that VEGF produce its neurotrophic effects. Conversely, VEGF stimulates BDNF release and requires BDNF signaling to produce its neurotrophic effects.
"This observation may have important clinical implications: VEGF inhibitors are widely used to treat various cancers and may be badociated with an increased risk of depression and cognitive impairment sometimes referred to as" chemotherapy fog ".
"Since most antidepressant effects are mediated by BDNF, and therefore VEGF, how should we treat these forms of depression and cognitive impairment?" The answer to this question might draw us to antidepressant-independent effects of BDNFs and new insights into the biology and treatment of depression, "said John Krystal, MD, editor-in-chief of Biological psychiatry.
The results provide the first evidence that the reciprocal interdependence of BDNF and VEGF plays a crucial role in their rapid effects similar to those of antidepressants, revealing the key mechanisms of ketamine, which requires both BDNF and VEGF . The results also highlight avenues for research to better understand how each of the factors can affect a person's risk of depression or its response to antidepressants.
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Notes to editors
The article is entitled "Neurotrophic and Antidepressant Actions of a Neurotrophic Factor Derived from the Brain Requiring Vascular Endothelial Growth Factor", by Satoshi Deyama, Eunyoung Bang, Taro Kato, Li Xiao-Yuan Li and Ronald S. Duman (https: /
Copies of this document are available upon request for accredited journalists. please contact Rhiannon Bugno at [email protected] or +1 214 648 0880. Journalists wishing to interview authors may contact Ronald S. Duman at [email protected] or +1 203 -974 to 7726.
Affiliations of authors and disclosure of financial information and conflicts of interest are available in the article.
John H. Krystal, MD, is Director of the Department of Psychiatry at Yale University School of Medicine, Head of the Yale-New Haven Hospital Psychiatry Department, and Psychiatrist of Health System Research. VA Connecticut. Its financial and conflict of interest information is available here.
Sure Biological psychiatry
Biological psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in areas that study the nature, causes, mechanisms, and treatments of thought, emotion, or behavioral disorders. In keeping with this mission, this peer-reviewed, rapid-publication international journal publishes fundamental and clinical contributions from all disciplines and fields of research relevant to the pathophysiology and treatment of major psychiatric disorders.
The journal publishes new findings from original research that represent a significant new advance or significant impact on the ground, particularly those dealing with genetic and environmental risk factors, neural circuits and neurochemistry, and important new therapeutic approaches. Criticism and commentary focused on current research and interest topics are also encouraged.
Biological psychiatry is one of the most selective and most cited journals in the field of psychiatric neuroscience. It is ranked 6th out of 142 titles in psychiatry and 9th of 261 Neuroscience titles in the journal Citations Reports® published by Clarivate Analytics. The 2017 impact factor score for Biological psychiatry is 11,982. http: // www.
About Elsevier
Elsevier is a global information badytics company that helps institutions and professionals advance health care, open science and performance for the benefit of humanity. Elsevier provides solutions and digital tools in the areas of Strategic Research Management, R & D Performance, Clinical Decision Support and Vocational Training, including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes more than 2,500 digitized journals, including The lancet and Cell, more than 38,000 titles of ebooks and many iconic reference books, including Gray & # 39; s Anatomy. Elsevier is part of RELX Group, a global provider of information and badytics for professionals and business customers across all industries. http: // www.
Media contact
Rhiannon Bugno, Writing
Biological psychiatry
+1 214 648 0880
[email protected]
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