{"id":2868,"date":"2025-06-21T16:58:11","date_gmt":"2025-06-21T16:58:11","guid":{"rendered":"https:\/\/www.europesays.com\/us\/2868\/"},"modified":"2025-06-21T16:58:11","modified_gmt":"2025-06-21T16:58:11","slug":"how-ptsd-disrupts-brain-cell-communication","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/2868\/","title":{"rendered":"How PTSD Disrupts Brain Cell Communication"},"content":{"rendered":"<p><strong>Summary: <\/strong>A new study has examined brains affected by PTSD at the single-cell level, uncovering distinct genetic alterations that may drive the disorder. Researchers focused on the dorsolateral prefrontal cortex, a brain region tied to emotional regulation, analyzing individual cell nuclei to map communication differences across PTSD, major depression, and control brains.<\/p>\n<p>They found impaired signaling in inhibitory neurons in PTSD, potentially explaining hyperarousal symptoms, and opposing patterns of microglial activity in PTSD versus depression. Vascular endothelial cells in PTSD brains also showed signs of dysfunction, possibly increasing stress hormone exposure.<\/p>\n<p><strong>Key Facts:<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li><strong>Inhibitory Neuron Disruption:<\/strong> PTSD brains showed decreased communication from inhibitory neurons, possibly causing hyperexcitable, overreactive brain states.<\/li>\n<li><strong>Microglia and Endothelial Differences:<\/strong> Microglia were overactive in depression but underactive in PTSD; endothelial cells in PTSD brains were also genetically altered, affecting stress hormone access.<\/li>\n<li><strong>New Therapeutic Pathways:<\/strong> The study identified gene pathways that could be targeted with precision drugs developed specifically for PTSD.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>Yale<\/p>\n<p><strong>The human brain is made up of billions of interconnected cells that are constantly talking to each other. <\/strong><\/p>\n<p>A new\u00a0Nature\u00a0study zooms in to the single-cell level to see how this cellular communication may be going wrong in brains affected by post-traumatic stress disorder (PTSD).<\/p>\n<p>  <img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"799\" src=\"https:\/\/www.europesays.com\/us\/wp-content\/uploads\/2025\/06\/PTSD-cell-neurosicnec.jpg\" alt=\"This shows a brain.\"  \/> Unlike Alzheimer\u2019s disease and Parkinson\u2019s disease, which are associated with noticeable changes to the brain when imaged, scientists know very little about the neurobiological mechanisms underlying PTSD. Credit: Neuroscience News<\/p>\n<p>Until recently, researchers did not have the technology to study genetic variation within individual cells.<\/p>\n<p>But now that it\u2019s available, a team led by\u00a0Matthew Girgenti, PhD, assistant professor of psychiatry at Yale School of Medicine, has been analyzing brain cells to uncover genetic variants that might be associated with psychiatric diseases such as major depressive disorder (MDD) and PTSD.<\/p>\n<p>Their latest study is one of the first to examine a major psychiatric disorder, PTSD, at the single-cell level.<\/p>\n<p>For years, doctors have been prescribing antidepressants to treat the condition because there are currently no drugs specifically designed for PTSD.<\/p>\n<p>Girgenti hopes that identifying novel molecular signatures associated with the psychiatric disease can help researchers learn how to develop new drugs or repurpose existing ones to treat it more effectively.<\/p>\n<p>\u201cWe\u2019re trying to figure out what\u2019s gone wrong in psychiatric disorders so that we can understand the neurobiological mechanisms that are in play in these diseases,\u201d he says.<\/p>\n<p>\u201cThe hope is that we can identify areas where we can potentially treat them\u2014that\u2019s the ultimate goal.\u201d<\/p>\n<p>For the new study, the researchers used postmortem human brain tissue from donors with and without PTSD.<\/p>\n<p>They also analyzed tissue from individuals who had been diagnosed with MDD\u2014which is often diagnosed in people with PTSD\u2014to better understand both the commonalities and where molecular mechanisms diverge between the conditions.<\/p>\n<p>Specifically, they looked at the dorsolateral prefrontal cortex, the region of the brain associated with executive functioning and emotional regulation.<\/p>\n<p>\u201cIt\u2019s the most uniquely human region of the brain,\u201d Girgenti explains.<\/p>\n<p>Across all three groups, the researchers isolated individual cells from this brain region, paying particular attention to the nuclei, which package the cells\u2019 DNA and make RNA. This allowed the team to observe genetic variation across the groups.<\/p>\n<p>Key genome alterations revealed in brains with PTSD and MDD<\/p>\n<p>Among brains with PTSD, the analyses revealed gene alterations in a type of neuron known as inhibitory neurons.<\/p>\n<p>\u201cThese are the fine-tuning neurons,\u201d says Girgenti.<\/p>\n<p>They regulate other neurons and prevent them from overfiring.<\/p>\n<p>In brains with PTSD and MDD, the team observed a decrease in the amount of communication from these neurons. The researchers believe that this decrease in communication may contribute to a hyperexcitable state in the prefrontal cortex.<\/p>\n<p>Following a traumatic event, this hyperexcitability could cause symptoms typically associated with PTSD such as hyperarousal (overreactive fight-or-flight response) and nightmares.<\/p>\n<p>The researchers also discovered differences in the microglia, which are the brain\u2019s immune cells. Interestingly, they found that these cells were overcommunicating in brains with MDD, but under communicating in those with PTSD.<\/p>\n<p>\u201cPTSD and MDD are generally very similar to each other and have a lot of shared genetic variability,\u201d Girgenti says.<\/p>\n<p>\u201cThis is a finding that seems to differentiate the two.\u201d His team hopes to further investigate these differences and how they might drive the two disorders.<\/p>\n<p>Furthermore, they found that brains with PTSD also had genome alterations associated with dysregulated endothelial cells. These cells are part of the brain\u2019s vasculature and interact with the rest of the body. Prior research has shown that individuals with PTSD have elevated levels of stress hormones, which travel to the brain through blood vessels.<\/p>\n<p>\u201cWe think there could be an increase in the amount of stress hormone that\u2019s getting into the brain because these endothelial cells are compromised,\u201d says Girgenti.<\/p>\n<p>Unlocking secrets of the brain to inform new therapies<\/p>\n<p>Unlike Alzheimer\u2019s disease and Parkinson\u2019s disease, which are associated with noticeable changes to the brain when imaged, scientists know very little about the neurobiological mechanisms underlying PTSD. By zooming in to the molecular level, Girgenti hopes these insights will help lead to better therapies for the disorder.<\/p>\n<p>\u201cWe\u2019ve already identified pathways\u2014pathways refer to how genes talk to each other\u2014that we think are targetable by particular drugs,\u201d he says.<\/p>\n<p>\u201cThis was only made possible by looking at those individual cells and those individual molecular changes. Now we have to try and find drugs that will reverse that.\u201d<\/p>\n<p>In future studies, Girgenti\u2019s team plans to examine other regions in the brain that might be involved in PTSD pathology such as the hypothalamus, which regulates the production of stress hormones.<\/p>\n<p>\u201cThe dorsolateral prefrontal cortex has been very well studied,\u201d says Girgenti.<\/p>\n<p>\u201cBut there are other regions of the brain that we know a lot less about, and they\u2019re just as likely to hold secrets for what is wrong. And there could be even better regions to look at when it comes to therapy.\u201d<\/p>\n<p><strong>Funding: <\/strong>The research reported in this news article was supported by the Department of Veterans\u00a0Affairs, the Brain and Behavior Research Foundation, the American Foundation for Suicide Prevention, the State of Connecticut\u2019s Department of Mental Health and Addiction Services, the National Institutes of Health (awards R01AA031017, DP1DA060811, R01NS128523, and R01HG012572) and Yale University.<\/p>\n<p>The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.<\/p>\n<p>About this PTSD and neuroscience research news<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"https:\/\/medicine.yale.edu\/ysm\/profile\/isabella-backman\/#links-details-section\" target=\"_blank\" rel=\"noreferrer noopener\">Isabella Backman<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/medicine.yale.edu\/\" target=\"_blank\" rel=\"noreferrer noopener\">Yale<\/a><br \/><strong>Contact: <\/strong>Isabella Backman \u2013 Yale <br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research: <\/strong>Open access.<br \/>\u201c<a href=\"https:\/\/www.nature.com\/articles\/s41586-025-09083-y\" target=\"_blank\" rel=\"noreferrer noopener\">Single-cell transcriptomic and chromatin dynamics of the human brain\u00a0in PTSD<\/a>\u201d by\u00a0Matthew Girgenti et al. Nature<\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>Single-cell transcriptomic and chromatin dynamics of the human brain\u00a0in PTSD<\/strong><\/p>\n<p>Post-traumatic stress disorder (PTSD) is a polygenic disorder occurring after extreme trauma exposure. Recent studies have begun to detail the molecular biology of PTSD.<\/p>\n<p>However, given the array of PTSD-perturbed molecular pathways identified so far, it is implausible that a single cell type is responsible.<\/p>\n<p>Here we profile the molecular responses in over two million nuclei from the dorsolateral prefrontal cortex of 111 human brains, collected post-mortem from individuals with and without PTSD and major depressive disorder.<\/p>\n<p>We identify neuronal and non-neuronal cell-type clusters, gene expression changes and transcriptional regulators, and map the epigenomic regulome of PTSD in a cell-type-specific manner.<\/p>\n<p>Our analysis revealed PTSD-associated gene alterations in inhibitory neurons, endothelial cells and microglia and uncovered genes and pathways associated with glucocorticoid signalling, GABAergic transmission and neuroinflammation.<\/p>\n<p>We further validated these findings using cell-type-specific spatial transcriptomics, confirming disruption of key genes such as\u00a0SST\u00a0and\u00a0FKBP5.<\/p>\n<p>By integrating genetic, transcriptomic and epigenetic data, we uncovered the regulatory mechanisms of credible variants that disrupt PTSD genes, including\u00a0ELFN1,\u00a0MAD1L1\u00a0and\u00a0KCNIP4, in a cell-type-specific context.<\/p>\n<p>Together, these findings provide a comprehensive characterization of the cell-specific molecular regulatory mechanisms that underlie the persisting effects of traumatic stress response on the human prefrontal cortex.<\/p>\n","protected":false},"excerpt":{"rendered":"Summary: A new study has examined brains affected by PTSD at the single-cell level, uncovering distinct genetic alterations&hellip;\n","protected":false},"author":3,"featured_media":2869,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[827,815,3810,517,829,831,1737,3811,159,67,132,68,3812],"class_list":{"0":"post-2868","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-brain-research","9":"tag-genetics","10":"tag-memory","11":"tag-mental-health","12":"tag-neurobiology","13":"tag-neuroscience","14":"tag-psychology","15":"tag-ptsd","16":"tag-science","17":"tag-united-states","18":"tag-unitedstates","19":"tag-us","20":"tag-yale"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/114722419684002237","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/2868","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=2868"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/2868\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/2869"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=2868"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=2868"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=2868"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}