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## Posttraumatic stress disorder (PTSD) and the Role of Glucocorticoids

Posttraumatic stress disorder (PTSD) is a debilitating condition that arises after experiencing traumatic events. While many people experience trauma, only about 25-35% develop PTSD. Understanding the factors that make certain individuals more susceptible is crucial for both prevention and treatment.

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## New Insights into the Influence of Glucocorticoids on PTSD

A new study led by Carmen Sandi and Simone Astori at EPFL now reveals how the development of PTSD is influenced by glucocorticoids, hormones that our body releases in response to stress, like cortisol. The work provides significant insights into the behavioral and biological traits associated with PTSD vulnerability.

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## Understanding Glucocorticoid Levels and PTSD

“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.”

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## The Role of Glucocorticoids in PTSD Symptoms

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.

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## Causal Evidence of Glucocorticoid Involvement in PTSD

“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.”

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## Mechanistic Evidence of Glucocorticoid Involvement in 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.”

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