Why Doesn’t Everybody Develop PTSD?

Posttraumatic stress disorder (PTSDPost-traumatic stress disorder (PTSD) is a psychiatric disorder that develops in some people who have experienced or witnessed a shocking, scary, or dangerous event.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>PTSD) is a serious mental health condition triggered by exposure to traumatic events. While many people experience trauma, only about 25-35% develop PTSD. Research into why certain individuals are more prone to developing PTSD is essential for both preventing and treating the disorder.

A recent study conducted by Carmen Sandi and Simone Astori at the École Polytechnique Fédérale de Lausanne (EPFL) has shed light on the role of glucocorticoids in PTSD development. Glucocorticoids are stress hormones, such as cortisol, that the body releases in response to stress. This study offers significant insights into the behavioral and biological characteristics that may increase an individual’s risk of developing PTSD.

Investigating Pre-Trauma Traits

“There are considerable differences in the levels of glucocorticoids that individuals release to the bloodstream when stressed,” says Carmen Sandi. “Low glucocorticoid levels are frequently observed in PTSD patients following trauma exposure and were initially suspected to be a consequence of trauma exposure.”

She continues: “The possibility that this could be a trait constituting a preexisting PTSD risk factor has been an outstanding open question for many years, but tackling it has been challenging due to the difficulties of both collecting biological measures before trauma exposure, and having access to relevant animal models in which the causal role of these traits can be investigated.”

To explore how a reduced hormonal response to stress might be linked to PTSD symptoms, the researchers used a genetically selected rat model that mimics people with blunted responses to cortisol. To do this, the team used MRI scans to measure the volume of different brain regions, trained rats to associate a cue with fear, recorded their sleep patterns, and measured their brain activity.

By combining these methods, the researchers discovered that a blunted responsiveness to glucocorticoids led to a “correlated multi-trait response” that includes impaired fear extinction (in males), reduced hippocampal volume, and rapid-eye-movement sleep disturbances.

To explain the terms: Fear extinction is a process by which a conditioned fear response diminishes over time; problems with fear extinction are a hallmark of PTSD. Rapid-eye movement is crucial for memory consolidation, and disturbances in this type of sleep pattern have long been associated with PTSD.

Further Research and Implications

But the study didn’t end there: the researchers treated the rats with the equivalent of human cognitive and behavioral therapy to reduce their learned fears. After that, they gave the rats corticosterone. As a result, both excessive fear and disturbances in rapid-eye-movement sleep receded. Not only that, but the increased levels of the stress-related neurotransmitter norepinephrine in the brain also returned to normal.

“Our study provides causal evidence of a direct implication of low glucocorticoid responsiveness in the development of PTSD symptomatology following exposure to traumatic experiences, i.e., impaired fear extinction,” says Carmen Sandi. “In addition, it shows that low glucocorticoids are causally implicated in the determination of other risk factors and symptoms that were until now only independently related to PTSD.”

Silvia Monari, the study’s first author, adds: “In a nutshell, we present mechanistic evidence – previously missing – that having low glucocorticoids such as cortisol in humans is a condition for causally predisposed individuals to present all to-date vulnerability factors for developing PTSD, and causally involved in deficits to extinguish traumatic memories.”

Reference: “Blunted Glucocorticoid Responsiveness to Stress Causes Behavioral and Biological Alterations That Lead to Posttraumatic Stress Disorder Vulnerability” by Silvia Monari, Isabelle Guillot de Suduiraut, Jocelyn Grosse, Olivia Zanoletti, Sophie E. Walker, Michel Mesquita, Tobias C. Wood, Diana Cash, Simone Astori and Carmen Sandi, 23 September 2023, Biological Psychiatry.
DOI: 10.1016/j.biopsych.2023.09.015

The study was funded by the Swiss National Science Foundation, the EU 7th Framework Programme for Research, ERA-NET Neuron, and EPFL.