Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic
J. Krystal, Chadi G. Abdallah, Lynnette A. Averill, B. Kelmendi, Ilan Harpaz-Rotem, Gerard Sanacora, Steven M. Southwick, Ronald S. Duman
Current Psychiatry Reports August 26, 2017 DOI: 10.1007/s11920-017-0829-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Esketamine Ketamine PTSD |
| Key findings | The authors propose that PTSD may be a "synaptic disconnection syndrome," in which stress-related loss of synaptic connectivity contributes to the disorder's symptoms. They suggest this perspective is clinically important and may explain how ketamine, a potential rapid-acting PTSD treatment, works in part by restoring synaptic connectivity. |
Abstract
Purpose of ReviewStudies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose of this review is to highlight the potential clinical importance of an often-neglected consequence of stress models in animals that may be relevant to PTSD: the stress-related loss of synaptic connectivity.Recent FindingsHere, we will briefly review evidence that PTSD might be a “synaptic disconnection syndrome” and highlight the importance of this perspective for the emerging therapeutic application of ketamine as a potential rapid-acting treatment for this disorder that may work, in part, by restoring synaptic connectivity.SummarySynaptic disconnection may contribute to the profile of PTSD symptoms that may be targeted by novel pharmacotherapeutics.
Comparable studies
Other narrative reviews on ketamine for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. | 2024 | Narrative state-of-the-art review | |
| Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation. | 1999 | Review | |
| The Psychedelic Future of Post-Traumatic Stress Disorder Treatment | 2024 | Comprehensive review | |
| Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation. | 2022 | Review | |
| The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. | 2023 | Review |
Citations in the library
Cited by 39
- Reviewing the Potential of Psychedelics for the Treatment of PTSD The International Journal of Neuropsychopharmacology March 12, 2020
- A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. American Journal of Psychiatry January 5, 2021
- The Psychedelic Future of Post-Traumatic Stress Disorder Treatment Current Neuropharmacology January 5, 2024
- Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation. Pharmacology & Therapeutics November 1, 2022
- The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. Therapeutic Advances in Psychopharmacology 2023
and 34 more in the library
Cites 10
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- mTOR activation is required for the antidepressant effects of mGluR2/3 blockade The International Journal of Neuropsychopharmacology November 24, 2011
- The role of adipokines in the rapid antidepressant effects of ketamine. Molecular Psychiatry January 2017
and 5 more in the library