summary: Researchers have discovered how stress-inducing hormones such as cortisol influence the likelihood of developing PTSD.
Using a rat model with a blunted hormonal response to stress, they observed traits associated with PTSD, including impaired fear extinction, decreased hippocampal volume, and sleep disturbances.
Treatment combining cognitive therapy and corticosterone helped reduce these symptoms, providing insight into potential interventions.
Important facts:
- People with low levels of glucocorticoids, such as cortisol, are more likely to develop PTSD after a traumatic event.
- The study found that blunted glucocorticoid responses lead to PTSD-related symptoms such as fear extinction disorder and sleep disturbances.
- Increasing glucocorticoid levels after trauma may reduce PTSD symptoms and improve recovery.
sauce: EPFL
Post-traumatic stress disorder (PTSD) is a debilitating condition that occurs after experiencing a traumatic event.
Many people experience trauma, but only about 25-35% develop PTSD. Understanding the factors that make certain people more susceptible is important for both prevention and treatment.
A new study led by EPFL’s Carmen Sandi and Simone Astori explores how the development of PTSD is influenced by glucocorticoids (hormones that our bodies release in response to stress, such as cortisol). revealed.
This study provides important insights into the behavioral and biological characteristics associated with PTSD vulnerability.
“The levels of glucocorticoids released into the bloodstream during times of stress vary considerably from person to person,” says Carmen Sandy.
“Decreased glucocorticoid levels are frequently observed in PTSD patients after traumatic exposure and were initially suspected to be a result of traumatic exposure.”
She continues: “The possibility that this is a trait that constitutes a pre-existing PTSD risk factor has been an open question for many years, but collecting and accessing biological measurements prior to exposure to trauma “This problem has been difficult to tackle because both are difficult. We aim to study relevant animal models that allow us to investigate the causal relationships between these traits.”
To investigate how reduced hormonal responses to stress are related to PTSD symptoms, researchers used a genetically selected rat model that mimics people with a blunted response to cortisol. .
To do this, the team used MRI scans to measure the volume of different brain regions, trained the rats to associate cues with fear, recorded sleep patterns, and measured brain activity.
By combining these methods, the researchers found that a blunted response to glucocorticoids could lead to “correlated problems” such as impaired fear extinction (in men), reduced hippocampal volume, and rapid eye movement sleep disturbances. It was discovered that it caused a “polytrait reaction.”
To explain the term, fear extinction is the process by which a conditioned fear response decreases over time. Problems with fear extinction are a hallmark of PTSD. Rapid eye movements are essential for memory consolidation, and disturbances in this type of sleep pattern have long been associated with PTSD.
But the research didn’t end there. The researchers gave the rats a treatment equivalent to human cognitive and behavioral therapy to reduce their learned fear. The rats were then given corticosterone.
As a result, both excessive fear and rapid eye movement sleep disorder receded. Not only that, the increased levels of the stress-related neurotransmitter noradrenaline in the brain also returned to normal.
“Our study provides causal evidence of a direct effect of reduced glucocorticoid reactivity on the development of PTSD symptoms after exposure to a traumatic event, namely impaired fear extinction.” Carmen Sandy says.
“Furthermore, we show that lower glucocorticoids have a causal role in determining other risk factors and symptoms that were previously only independently associated with PTSD.”
Sylvia Monali, lead author of the study, added: “In short, a previously missing mechanism is that reduction in glucocorticoids such as cortisol in humans is a condition in which causally predisposed individuals exhibit all of the previous vulnerability factors for developing PTSD. “We present evidence that there is a causal link to deficits in order to erase traumatic memories.” ”
About this PTSD research news
author: Nick Papagiorgio
sauce: EPFL
contact: Nick Papagiorgio – EPFL
image: Image credited to Neuroscience News
Original research: Open access.
“Blunted glucocorticoid reactivity to stress causes behavioral and biological changes and predisposes to post-traumatic stress disorderWritten by Carmen Sandy et al. biological psychiatry
abstract
Blunted glucocorticoid reactivity to stress causes behavioral and biological changes and predisposes to post-traumatic stress disorder
background
Understanding why only a proportion of trauma-exposed individuals develop post-traumatic stress disorder is important for advancing clinical strategies. Several behavioral (deficiencies in fear extinction) and biological (slower glucocorticoid levels, smaller hippocampal size, rapid eye movement sleep) [REMS] characteristics (such as disability) have been identified as potential vulnerability factors. However, it is unclear whether and to what extent these characteristics are interrelated, and whether one of them can causally cause the other.
method
In a genetically selected rat model with reduced corticosterone responsiveness to stress, we combined in vitro magnetic resonance imaging, cued fear conditioning, polysomnography recording and in vivo photometry to investigate the association of post-traumatic stress disorder. We investigated the behavioral characteristics of the animals.
result
We show that genetic selection for blunted glucocorticoid reactivity causes correlated polytrait responses, such as fear extinction deficits (observed in men but not women), small hippocampal volumes, and REMS impairments, and that their interaction The results showed support for the relationship. Fear extinction deficits and associated REMS disruptions can be normalized by post-extinction corticosterone administration, suggesting that glucocorticoid deficiency is one of the two core dangers associated with post-traumatic stress disorder. This suggests a causal relationship between factors and symptoms. Furthermore, the decrease in REMS was accompanied by an increase in norepinephrine levels in the hippocampal dentate gyrus, which was also reversed by corticosterone treatment after extinction.
conclusion
Our results point to a predominant role of glucocorticoid deficiency, rather than a contribution of reduced hippocampal volume, which causes both REMS alterations and associated deficits in enhanced fear extinction, with blunted glucocorticoids contributing to fear extinction. This suggests that they are causally involved in the persistence of the neurophysiological impairments that lead to the deficits.
