Summary: Researchers have discovered the impact of stress-induced hormones, such as cortisol, on the development of PTSD. By using a rat model that has a reduced hormonal response to stress, scientists observed impaired fear extinction, decreased hippocampal volume, and sleep disruptions, which are all characteristics linked to PTSD.
A treatment approach combining cognitive therapy with corticosterone has shown promise in alleviating these symptoms, offering valuable insights into potential interventions.
Key Facts:
- Individuals with lower glucocorticoid levels, like cortisol, are more prone to developing PTSD following traumatic events.
- Research has shown that diminished glucocorticoid responses can lead to PTSD-associated symptoms, including impaired fear extinction and sleep disturbances.
- Increasing glucocorticoid levels post-trauma may potentially reduce PTSD symptoms and enhance recovery.
Source: EPFL
Posttraumatic stress disorder (PTSD) can be a debilitating condition following traumatic experiences. While many people experience trauma, only about 25-35% develop PTSD. Understanding the factors that render certain individuals more susceptible is crucial for prevention and treatment.
A recent study led by Carmen Sandi and Simone Astori at EPFL has shed light on how PTSD development is influenced by glucocorticoids, hormones released in response to stress, like cortisol.
The study provides significant insights into the behavioral and biological traits linked to PTSD vulnerability.
“There are notable differences in the levels of glucocorticoids that individuals release in response to stress,” 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 adds, “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 further explore the link between a reduced hormonal response to stress and PTSD symptoms, the researchers used a genetically selected rat model that mimics individuals with blunted responses to cortisol.
The team employed MRI scans to measure the volume of different brain regions, trained rats to connect a cue with fear, recorded their sleep patterns, and analyzed their brain activity.
The scientists discovered that a blunted response to glucocorticoids led to a “correlated multi-trait response” consisting of impaired fear extinction (in males), reduced hippocampal volume, and rapid-eye movement sleep disturbances.
Furthermore, the researchers treated the rats with the human equivalent of cognitive and behavioral therapy to reduce their learned fears. Subsequently, they administered corticosterone to the rats.
As a result, both excessive fear and disturbances in rapid-eye movement sleep decreased. Additionally, the elevated levels of the stress-related neurotransmitter norepinephrine in the brain 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.”
About this PTSD research news
Author: Nik Papageorgiou
Source: EPFL
Contact: Nik Papageorgiou – EPFL
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Blunted glucocorticoid responsiveness to stress causes behavioral and biological alterations that lead to posttraumatic stress disorder vulnerability” by Carmen Sandi et al. Biological Psychiatry
Abstract
Blunted glucocorticoid responsiveness to stress causes behavioral and biological alterations that lead to posttraumatic stress disorder vulnerability
Background
Understanding why only a subset of trauma-exposed individuals develop posttraumatic stress disorder is critical for advancing clinical strategies. A few behavioral (deficits in fear extinction) and biological (blunted glucocorticoid levels, small hippocampal size, and rapid-eye-movement sleep [REMS] disturbances) traits have been identified as potential vulnerability factors. However, whether and to what extent these traits are interrelated and whether one of them could causally engender the others are not known.
Methods
In a genetically selected rat model of reduced corticosterone responsiveness to stress, we explored posttraumatic stress disorder–related biobehavioral traits using ex vivo magnetic resonance imaging, cued fear conditioning, and polysomnographic recordings combined with in vivo photometric measurements.
Results
We showed that genetic selection for blunted glucocorticoid responsiveness led to a correlated multitrait response, including impaired fear extinction (observed in males but not in females), small hippocampal volume, and REMS disturbances, supporting their interrelatedness. Fear extinction deficits and concomitant disruptions in REMS could be normalized through postextinction corticosterone administration, causally implicating glucocorticoid deficiency in two core posttraumatic stress disorder–related risk factors and manifestations. Furthermore, reduced REMS was accompanied by higher norepinephrine levels in the hippocampal dentate gyrus that were also reversed by postextinction corticosterone treatment.
Conclusions
Our results indicate a predominant role for glucocorticoid deficiency over the contribution of reduced hippocampal volume in engendering both REMS alterations and associated deficits in fear extinction consolidation, and they causally implicate blunted glucocorticoids in sustaining neurophysiological disturbances that lead to fear extinction deficits.
