iScience
June 20, 2025
Michelle K Piazza, Abigael R Weit, Ege T Kavalali et al.
2 citations
Ketamine induces antidepressant action via upregulation of hippocampal brain-derived neurotrophic factor (BDNF) expression and TrkB receptor signaling. Rett syndrome (RTT), a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2), is associated with decreased BDNF expression. Although treatment with ketamine or LM22A-4, a TrkB receptor agonist, improves...
Science
May 8, 2025
Z Zack Ma, Natalie J Guzikowski, Ji-Woon Kim et al.
44 citations
Repeated ketamine treatment to maintain a rapid antidepressant effect can lead to side effects over time, highlighting an unmet clinical need for sustaining this drug's antidepressant action from a single administration. Ketamine-induced synaptic potentiation at CA3-CA1 synapses has been proposed to be a key synaptic substrate for antidepressant action. Here, we found that ketamine-induced...
Neuropsychopharmacology
November 1, 2024
Ji-Woon Kim, Benjamin Kleinfelter, Ege T Kavalali et al.
3 citations
Prevailing hypotheses on the mechanisms of antidepressant action posit that antidepressants directly counteract deficiencies in major neurotransmitter signaling systems that underlie depression. The rapidly acting antidepressant ketamine has been postulated to correct excess glutamatergic signaling via glutamatergic antagonism leading to the rescue of neuronal structural deficits and reversal...
Neuropsychopharmacology
October 1, 2024
Michelle K Piazza, Ege T Kavalali, Lisa M Monteggia
21 citations
Synaptic plasticity occurs via multiple mechanisms to regulate synaptic efficacy. Homeostatic and Hebbian plasticity are two such mechanisms by which neuronal synapses can be altered. Although these two processes are mechanistically distinct, they converge on downstream regulation of AMPA receptor activity to modify glutamatergic neurotransmission. However, much remains to be explored regarding...
European Archives of Psychiatry and Clinical Neuroscience
September 29, 2024
Ege T Kavalali, Lisa M Monteggia
4 citations
The discovery of ketamine's rapid antidepressant action has generated intense interest in the field of neuropsychiatry. This discovery demonstrated that to alleviate the symptoms of depression, treatments do not need to elicit substantive alterations in neuronal circuitry or trigger neurogenesis, but rather drive synaptic plasticity mechanisms to compensate for the underlying pathophysiology....
Annual Review of Medicine
September 20, 2023
Ji-Woon Kim, Kanzo Suzuki, Ege T Kavalali et al.
105 citations
Major depressive disorder (MDD) is a leading cause of suicide in the world. Monoamine-based antidepressant drugs are a primary line of treatment for this mental disorder, although the delayed response and incomplete efficacy in some patients highlight the need for improved therapeutic approaches. Over the past two decades, ketamine has shown rapid onset with sustained (up to several days)...
Neuropsychopharmacology
July 24, 2023
John H. Krystal, Ege T Kavalali, Lisa M Monteggia
229 citations
Ketamine is an open channel blocker of ionotropic glutamatergic N -Methyl- D -Aspartate (NMDA) receptors. The discovery of its rapid antidepressant effects in patients with depression and treatment-resistant depression fostered novel effective treatments for mood disorders. This discovery not only provided new insight into the neurobiology of mood disorders but also uncovered fundamental...
Trends in molecular medicine
March 1, 2023
Ji-Woon Kim, Kanzo Suzuki, Ege T Kavalali et al.
Acute (R,S)-ketamine (ketamine) administration produces rapid antidepressant effects that in some patients can be sustained for several days to more than week. Ketamine blocks NMDA receptors to elicit specific downstream signaling that induces a novel form of synaptic plasticity in the hippocampus that has been linked to the rapid antidepressant action. These signaling events lead to subsequent...
Cell Reports
August 1, 2021
Pei-Yi Lin, Z. Z. Ma, Melissa Mahgoub et al.
97 citations
SUMMARY Ketamine produces rapid antidepressant action in patients with major depression or treatment-resistant depression. Studies have identified brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), as necessary for the antidepressant effects and underlying ketamine-induced synaptic potentiation in the hippocampus. Here, we delete BDNF or TrkB in...
Nature
June 15, 2011
Anita E. Autry, M. Adachi, E. Nosyreva et al.
Clinical studies consistently demonstrate that a single sub-psychomimetic dose of ketamine, an ionotropic glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder, although the underlying mechanism is unclear. Depressed patients report the alleviation of major depressive disorder symptoms...