Post-traumatic stress disorder ⋅ Inserm, From science to health

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that occurs after a traumatic event. They result in moral suffering and physical complications that profoundly alter personal, social and professional life. Faced with the same event, the risk of developing such disorders depends on pre-existing factors specific to the patients and the context in which the consequences of the event take place. Treatment essentially involves psychotherapy (cognitive-behavioral therapy, EMDR). Thanks to ongoing research, a better understanding of the mechanisms that favor the resurgence of painful memories will ultimately make it possible to prevent, relieve and even cure these disorders.

Dossier produced in collaboration with Pierre Gagnepain, researcher from the Memory and Forgetting team, within the Neuropsychology and Imaging of Human Memory Unit (U1077 Inserm/University of Caen Normandy/School of Advanced Studies), Caen

  • Understanding post-traumatic stress disorder

    Post-traumatic stress disorder (PTSD) develops after an extremely traumatic event and is manifested by its regular reliving, accompanied physical manifestations linked to the extreme emotion felt. They significantly alter personal, social and/or professional life.

    These psychiatric disorders occur in children or adults who have been exposed to a significant event, such as a threat of imminent death, serious injury or bodily harm that they have experienced or witnessed. PTSD can also occur after the announcement of a violent or unexpected death, or a serious event affecting a loved one.

    Also, individuals with PTSD can be people who have participated in military combat, been victims of physical or sexual assault, natural disaster, or hostage taking, as well as professionals who have intervened on disaster sites, parents who have lost a child or even witnesses of an accident, an attack or a natural disaster. All have in common to have experienced this event as a factor of intense stress or dread, in the face of which they felt powerless.


    A disorder known since Antiquity

    Psychic traumas have been reported in soldiers since Antiquity. Interest in them then developed through military medicine in the 17th century. But it was the violence of the great international conflicts of the 20th century that would impose the deepening of knowledge on psychotraumatic disorders. At the same time, the description and study of similar disorders in civil society have been reported in the scientific literature as early as the 19th century.

    Nevertheless, the concept of post-traumatic stress disorder, or post-traumatic stress disorder, as we know it today, was not clinically defined until 1980, following the ravages of war. of Vietnam among American veterans.


    A high prevalence in certain populations

    The prevalence of PTSD would be 5 to 12% in the general population, but these data come mainly from studies carried out in the United States (the studies on the subject are more rare in France and in other countries). Moreover, these figures could be underestimated due to the lack of knowledge of the disorder and its incomplete presentations which may escape diagnosis.

    There is more data on certain specific populations, more often affected by PTSD (and therefore more studied). It is estimated, for example, that nearly a quarter of soldiers who have taken part in a war are affected by these disorders.

    Concerning direct or indirect witnesses of terrorist acts, several epidemiological investigations have recently been conducted in France, in collaboration with Inserm teams. Thus, 6 to 18 months after the January 2015 attacks (Charlie Hebdo, Hyper Kosher, Montrouge, Dammartin-en-Goële), 18% of witnesses presented with PTSD, with a prevalence ranging from 3% among nearby witnesses and up to 31% among people directly threatened (IMPACTS study). Disorders also concerned 3% of responders (police, caregivers, etc.), knowing that a significant proportion of all witnesses without PTSD presented with anxiety or depression related to the event. A similar survey was conducted after the November 2015 attacks (Paris, Saint-Denis): it showed a prevalence of PTSD of 54% among people directly threatened and almost as much among people who lost a loved one during these events. (ESPA-13 November study).

    Another study conducted following this series of attacks described that the general population could have developed PTSD without having directly witnessed or personally affected by collective traumatic events: the time spent viewing the images of these attacks on television was associated with an increased risk of developing specific post-traumatic stress symptoms, all else being equal.

    A diagnosis combining reliving, avoidance and neurovegetative activity

    Post-traumatic stress disorder ⋅ Inserm , Science for health

    The diagnosis of PTSD is made in a person who has faced a traumatic event when he presents several manifestations responsible for suffering and a significant alteration of social functioning and quality of life:

    In the immediate aftermath of the event, these signs are considered a state of acute stress. We speak of acute PTSD when they persist for more than 4 weeks. Most people will recover from these disorders within 3 months of the event, but around 20% will develop a chronic form of the syndrome.

    It should also be noted that, while they generally appear immediately, after a few days, PTSD sometimes sets in more gradually, forming late, after several weeks, months or years.

    Everyone at risk of PTSD?

    PTSD results from an interaction between three major groups of contributing factors:

    In any event, a person without any particular vulnerability factor may still develop PTSD in certain situations.


    From trauma to neurobiology: what mechanisms?

    Unlike non-traumatic memories, traumatic memories do not follow the usual procedure of analysis and distancing. Indeed, in TPST, the intensity of the event would be such that it causes hypermnesia on the emotional level, while hampering the constitution of episodic memory which makes it possible to verbalize and raise awareness of what is happening. This change can sometimes lead to partial amnesia about precisely how the episode unfolded. A posteriori, this alteration in the constitution of memory makes the individual incapable of putting the event at a distance by speech or consciousness. Only the emotions resurface, with a power similar to the initial event.

    These observations are corroborated by experiments carried out in animals, as well as by brain imaging: this reveals hyperactivity of the amygdala, the main site of emotional memory, and hypoactivity of the amygdala. hippocampus, involved in declarative memory. The plasticity of this structure also appears reduced, as does its volume. A decrease in hippocampal volume is also a factor of vulnerability to PTSD.

    Biologically, the mechanisms involved are governed by a disturbance of the hypothalamic-pituitary-adrenal axis, with an exacerbated release of various stress mediators, including cortisol, and a disturbance of various neuromediators (dopaminergic, glutamatergic …). The so-called “periaqueductal” gray matter, a set of neurons involved in defense and avoidance reactions, is particularly active.


    A powerful impact on daily life and health

    When left untreated, post-traumatic stress becomes chronic and associated with other types of manifestations: the individual complains of chronic fatigue and shows neither energy nor motivation to carry out the usual activities of his daily life. He often develops eating disorders (anorexia, bulimia, etc.), a disturbance in his emotional life and his libido.

    PTSD is often associated with other mental health conditions such as depression or anxiety. It has disabling repercussions on social, family and professional life. The suffering is such that it increases the risk of addiction to psychoactive substances or the risk of suicide.

    In addition, PTSD is associated with a state of chronic stress that will affect the somatic health of the individual: people who suffer from it have an increased risk of migraine, high blood pressure, gastric ulcer, dermatological diseases...

    Treatment: immediate and long-term care

    In order to prevent and limit the effects of stress, immediate help can be provided by psychiatrists, clinical psychologists or other professionals trained to listen. They are the ones who intervene in the emergency psychological support cells that are set up during traumatic events occurring in the public space. The support provided involves listening and psychosocial support, as well as material assistance and post-traumatic orientation. The situation is more complicated for people individually subjected to a traumatic event, because they do not always have the means to take steps to get help.

    After the event, the recommended first-line treatments are psychotherapies, for example cognitive-behavioural or EMDR (eye movement desensitization and reprocessing). Their goal is to limit the mental and behavioral avoidance that prevents the traumatic memory from being integrated and processed as a habitual memory.

    In terms of medication, sedatives, antidepressants or anxiolytics are often prescribed in addition to psychotherapy, depending on the patient's needs. However, they have a limited, purely symptomatic efficacy.

    For about one in five patients, there is a significant risk of seeing the patient relapse after appropriate treatment.

    Research challenges

    Deepen the understanding of neurobiological mechanisms

    Numerous studies have made it possible to advance knowledge of the mechanisms involved in the onset and chronicization of PTSD, but many still remain to be elucidated. The share of genetic and epigenetic mechanisms is particularly the subject of work that could explain part of the interindividual vulnerability to a traumatic event.

    On the genetic level, genome-wide genetic association studies (GWAS) conducted on large cohorts have made it possible to associate part of the resilience capacity (measured according to a validated score scale) with genetic variability. Several concern genes that regulate the hypothalamic-pituitary-adrenal axis, or others that code for inflammatory mediators. Similarly, on the epigenetic level, DNA methylation or histone acetylation at the level of certain regions could be associated with variability in the expression of genes at the cerebral level (genes involved in the transport of serotonin, the level of exposure to corticosteroids or neurotrophic factors, etc.).

    Neuroimaging data, and in particular those from functional neuroimaging, optogenetics, or chemogenetics, have made it possible to describe that PTSD is associated with an alteration in the activity and connectivity of certain neural circuits, especially those involved in fear and threat detection or reward processing.

    Deciphering the mechanism of reliving to better control it

    After a traumatic event, attempts to suppress or avoid the memory sometimes lead paradoxically to increase its resurgence. In order to minimize this mechanism, it is necessary to recontextualize the memory, so that it can be dissociated and placed at a distance from the initial emotions attached to it. Even if it is schematically established that the traumatic memory does not follow the usual circuit of analysis and distancing of non-traumatic memories, the role of the various underlying mechanisms remains to be elucidated: difficulty in forgetting the memory, poor control of its revival, memory updating disorders (allowing to integrate that the risk having caused the trauma is finished)… The most recent data indeed suggest that these various mechanisms would be involved in the persistence of the traumatic memory. However, this traumatic persistence has recently been associated with an inability to control and inhibit intrusive memories. A dysfunction of the prefrontal mechanism regulating activity from regions associated with memories, such as the hippocampus, and preventing their deletion and forgetting. These avenues constitute as many elements for considering the development of specific non-pharmacological treatments, which would make it possible to work on these difficulties.

    In addition, two approaches seem equally interesting. The first consists of administering corticosteroids for a few days or weeks following the traumatic event, in order to reduce the consequences of stress. The second aims to limit the consolidation of memories, that is to say the passage of the event from short-term memory to long-term memory, with a beta-blocker capable of penetrating the central nervous system, the propranolol. The molecule reduces the expression of fear and presumably also the consolidation of memory when it is reactivated. However, its precise mechanism of action remains to be deciphered.


    A research program around November 13

    In 2016, Inserm, the CNRS and HéSam Université set up a large transdisciplinary research program aimed at studying the impact of tragic events of November 13, 2015. Among the various projects of the program, the follow-up of a cohort of more than 1,000 volunteers is planned for 10 years. People directly affected by the attacks, directly or indirectly, as well as others who were not personally affected, will be interviewed at regular intervals by psychologists, psychopathologists, neuroscientists, but also by historians and sociologists.

    Another part of this program, entitled "Remember", focuses more specifically on people directly affected by the attacks, who may or may not suffer from post-traumatic stress disorder, as well as control people. Interviews and neuroimaging analyzes will provide a better understanding of the mechanisms of the resurgence of images and thoughts associated with the event. Ultimately, all of this work will provide valuable lessons on how memory is constituted and how individual memory is articulated with the constitution of collective memory.

    To find out more about the progress of this research project: Program 13-Novembre – progress report 5 years after the start of the project (press release of 10/11/21)


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