Molecular and cellular studies of PTSD: Postmortem transcriptome analysis and novel therapeutic targets.
Ronald S. Duman, Matthew J. Girgenti
Journal of Neuroscience Research March 2019 DOI: 10.1002/jnr.24306 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Ketamine PTSD |
| Keywords | Rna sequencing Glucocorticoid Prefrontal cortex |
| Key findings | Preliminary next-generation RNA sequencing of postmortem PTSD brain tissue identified PTSD-specific gene expression alterations in the prefrontal cortex, including the glucocorticoid-regulated genes FKBP5 and SGK1. The authors propose that altered SGK1 may contribute to synaptic changes in prefrontal cortex subregions, potentially leading to loss of inhibitory control and impaired fear extinction. They further discuss evidence that ketamine increases synapse number in the prefrontal cortex, enhances fear extinction in rodent models, and improves symptoms in PTSD patients. |
Abstract
The neurobiology of fear memory and extinction has been the subject of extensive research efforts that have increased our understanding of the brain regions, circuitry, and the cellular and molecular determinants of fear memory processes. However, the inability to access and directly study the brains of PTSD patients has made it difficult to translate the rodent fear memory studies to understand the neurobiological underpinnings of PTSD. The formation of a PTSD brain repository has recently been undertaken to address this issue. This will allow for high throughput gene expression and proteome analysis that can be coupled with epigenetic and genomic approaches to characterize the molecular alterations underlying PTSD. Preliminary studies using next generation RNA sequencing have identified PTSD specific gene expression alterations in the prefrontal cortex (PFC). The approaches used for transcriptome analysis and early findings regarding two glucocorticoid regulated genes of interest, FKBP5 and SGK1 are discussed, and the consequences of altered SGK1 are presented. Altered SGK1 could contribute to synaptic alterations in PFC subregions that could contribute to loss of inhibitory control and extinction of fear memories. Based on these findings, we discuss new studies demonstrating that ketamine can increase synapse number in the PFC and enhance the extinction of fear memory in rodent models and improve symptoms in PTSD patients. Continued molecular and cellular characterization of postmortem brain tissue of PTSD subjects will further define the neurobiology of PTSD and identify novel targets for safe and more efficacious treatments.
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
Cites 3
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014