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Post-traumatic stress disorder or PTSD is a psychiatric disorder frequently developed after a traumatic experience. The research carried out to date has made it possible to better understand the biological mechanisms to develop new therapeutic approaches.
Since Antiquity, stories of war and battle mentioned the presence of mental disorders in soldiers who fought. But only the advent of military medicine and the development of psychology eventually brought these types of trauma-related disorders to light. PTSD (post-traumatic stress disorder) is an anxiety disorder that develops weeks, months or even years after a traumatic event. Soldiers, victims and witnesses of war, physical and/or psychological violence are particularly affected. The intrusion of memories of the trauma (sudden flashbacks or nightmares), avoidance strategies (of places, of people) to counter their reminiscences, the state of hyperstimulation (hypervigilance, insomnia), as well as mood and behavioral disorders (apathy, anxiety, impaired memory, and lack of concentration) are hallmarks of PTSD. Epidemiological studies have shown that following the terrorist events in France in 2015, up to 54% of those directly affected developed PTSD-type disorders.
A better understanding of post-traumatic stress syndrome
This disorder can be, among other things, considered deregulation of the neural circuit responsible for fearful behavior. This circuit is made up of all the connections between the hippocampus, the amygdala, the prefrontal cortex, and the hypothalamus, within which two subcircuits exist: one controlling the learning of fear and the other of its forgetting. In the case of PTSD, the learning networks of fear are overactivated to the detriment of those of forgetting. Therefore, the imbalance between learning and forgetting causes a normal fear memory to become pathological. Studies in humans and animal models have shown that PTSD is linked to the hyperactivation of the amygdala, a brain region that "codes" the emotional valence of memory, and the hypoactivation of the hippocampus, which codes the context of an event. This imbalance between the amygdala and the hippocampus is at the core of traumatic memory, where the hypermnesia of certain salient events (a sound, a smell, or a sensation) cohabits with a hypomnesia of the event context preventing from remembering accurately. In such a case, the memories of the trauma arise spontaneously, even outside the framework of the initial trauma. Neuroimaging studies have also observed that the level of amygdala activity correlates with the strength of the symptoms experienced.
Figure adapted from Alexandra Kredlow et al., 2021.
In healthy people, the brain regions responsible for fear learning (amygdala, ACC) are controlled by other regions that regulate it (dlPFC, vmPFC) and associated with a specific memory (hippocampus), and thus set an adapted behavioral response (hypothalamus and brainstem) according to a threat. In people with PTSD, the loss of control by dlPFC and vmPFC on the amygdala and ACC leads to hypermnesia of certain elements of the traumatic memory. In addition, the hypoactivation of the hippocampus induces a deficit of contextualization, so that the fear response is no longer solely associated with the traumatic event. This is referred to as the over-generalization of memory, where particular facts are no longer bound to a specific time and place. Because of this imbalance, the hypothalamus and the brainstem are overactivated and induce exacerbated fear behaviors. dlPFC = dorsolateral prefrontal cortex, vmPFC = ventromedial prefrontal cortex, ACC = anterior cingulate cortex.
Various risk factors
People who experienced violence or abuse, especially during childhood, are particularly vulnerable to developing PTSD in adulthood. Genetics (the genes and associated mutations) and epigenetics (the regulation of gene expression) play also an important role. Several genes coding for receptors or modulators of the stress response show significant differences in people with PTSD and are responsible for the disrupted biological response to stress. According to some studies, trauma before the experience that triggered PTSD could permanently affect the expression of certain stress response genes, which would explain the greater prevalence of PTSD in these people. More surprisingly, genetic and epigenetic abnormalities have also been identified in genes involved in immunity or chronobiology (sleep cycles). Additionally, women are twice as affected as men, likely due to the role of sex hormones in risk assessment and resilience. Finally, while a reduced hippocampal volume was thought to be a consequence of PTSD, new studies have concluded the opposite. This anomaly would lead to a deficit of contextual memory in these people, increasing the risk of developing PTSD.
Therapeutic approaches of different types
The first therapeutic approach used mainly focused on the use of antidepressants, with a limited effect on the symptoms of PTSD. Propranolol, a molecule that blocks norepinephrine receptors, has shown variable results on PTSD symptoms, especially because the dosage but also the timing and duration of the treatment seem to be important factors requiring more research. However, taken soon after a trauma, propranolol appears to reduce the risk of developing PTSD. EMDR (Eye Movement Desensitization and Reprocessing) is an effective therapy in which patients, accompanied by their therapist, recall their traumas while performing rapid eye movements. Although the biological mechanisms involved are not well known, it is believed that these eye movements mimic those of the dream phase, during which our brain integrates acquired information. This therapy would therefore allow the brain to process the information of the traumatic event in a healthy way to form an accurate memory and provide a healthy response. The use of certain drugs sometimes referred to as psychedelics, such as ketamine and psilocybin, is a promising approach studied in the United States. It has shown positive effects in patients suffering from severe forms of depression and anxiety. Taking MDMA (the psychoactive component of ecstasy) following a precise protocol and guided by a psychotherapist, shows very encouraging effects in treating PTSD. By regulating cortisol and norepinephrine levels, and stimulating the release of oxytocin, a neurohormone responsible for attachment and feelings of trust, supervised intake of MDMA would regulate the emotional state of patients and help their brains get back to an optimal state of functioning where information of the traumatic event is correctly processed. Although still in the clinical study phase, this research could prove essential in the treatment of PTSD.
Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder that affects some victims and witnesses of dreadful events (wars, terrorist acts, accidents, physical and psychological violence). For example, nearly 54% of victims or witnesses of the 2015 attacks in France developed PTSD.
It is characterized by the intrusion of memories of the trauma (flashbacks and nightmares), avoidance, hypervigilance, as well as mood and memory disorders.
PTSD is characterized by a weak memory of different elements of the traumatic event caused by the dysregulation of the fear memory circuits where the amygdala is overactivated while the hippocampus is under-activated.
In people with PTSD, the two stress hormones cortisol and norepinephrine are dysregulated, affecting the functioning of many areas of the brain.
There are many risk factors (psychosocial, physiological, anatomical, genetic, and epigenetic) that increase vulnerability to the development of PTSD.
Several alternatives exist to reduce the symptoms of PTSD, based on medical treatments, psychological/behavioral therapies, or in combination.
- Alexandra Kredlow M, Fenster RJ, Laurent ES, Ressler KJ, Phelps EA. Prefrontal cortex, amygdala, and threat processing: implications for PTSD. Neuropsychopharmacology. 2022
- De Gregorio D, Aguilar-Valles A, Preller KH, Dov Heifets B, Hibicke M., Mitchell J. and Gobbi G. Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine. Journal of Neuroscience. 2021
- Giustino TF, Fitzgerald PJ, Maren S. Revisiting propranolol and PTSD: Memory erasure or extinction enhancement? Neurobiology of Learning and Memory. 2016
- Cain C. K., Maynard G. D., and Kehne J. H. Targeting memory processes with drugs to prevent or cure PTSD. Expert Opinion on Investigational Drugs. 2012
- Pitman RK, Rasmusson AM, Koenen KC, Shin LM, Orr SP, Gilbertson MW, Milad MR, Liberzon I. Biological studies of post-traumatic stress disorder. Nature Review Neuroscience. 2012
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