title: The role of glucocorticoids, catecholamines and endocannabinoids in the development of traumatic memories and posttraumatic stress symptoms in survivors of critical illness.
abstract: Critically ill patients are at an increased risk for traumatic memories and post-traumatic stress disorder (PTSD). Memories of one or more traumatic events play an important part in the symptom pattern of PTSD. Studies in long-term survivors of intensive care unit (ICU) treatment demonstrated a clear and vivid recall of traumatic experiences and the incidence and intensity of PTSD symptoms increased with the number of traumatic memories present. Preclinical evidence has clearly shown that the consolidation and retrieval of traumatic memories is regulated by an interaction between the noradrenergic, the glucocorticoid and the endocannabinoid system. Critically ill patients in the ICU frequently require treatment with adrenenergic or glucocorticoid drugs and often receive sedative medications; among them propofol is known to influence endocannabinoid signaling. Critical illness could therefore represent a useful model for investigating adrenergic, glucocorticoid as well as endocannabinoid effects on traumatic memory and PTSD development in stressed humans. The endocannabinoid system is an important regulator of HPA-axis activity during stress, an effect which has also been demonstrated in humans. Likewise, a single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene (the BclI-SNP), which enhances the sensitivity of the glucocorticoid receptors to cortisol and possibly HPA-axis feedback function, was associated with enhanced emotional memory performance in healthy volunteers. The presence of the BclI-SNP increased the risk for traumatic memories and PTSD symptoms in patients after ICU therapy and was linked to lower basal cortisol levels. A number of small studies have demonstrated that the administration of cortisol to critically ill or injured patients results in a significant reduction of PTSD symptoms after recovery without influencing the number of traumatic memories. These glucocorticoid effects can possibly be explained by a cortisol-induced temporary impairment in traumatic memory retrieval which has previously been demonstrated in both rats and humans. The hypothesis that stress doses of glucocorticoids or the pharmacologic manipulation of glucocorticoid-endocannabinoid interaction during traumatic memory consolidation and retrieval could be useful for prophylaxis and treatment of PTSD after critical illness should be tested in larger controlled studies.
authors.affiliation: Department of Anaesthesiology, University of Munich, Campus Grosshadern, 81377 Munich, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hauer
authors.affiliation: Department of Anaesthesiology, University of Munich, Campus Grosshadern, 81377 Munich, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Kaufmann
authors.affiliation: Department of Anaesthesiology, University of Munich, Campus Grosshadern, 81377 Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Strewe
authors.affiliation: Department of Anaesthesiology, University of Munich, Campus Grosshadern, 81377 Munich, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Briegel
authors.affiliation: Department of Anaesthesiology, University of Munich, Campus Grosshadern, 81377 Munich, Germany; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.affiliation: Department of Anaesthesiology, University of Munich, Campus Grosshadern, 81377 Munich, Germany. Electronic address: gustav.schelling@med.uni-muenchen.de.
authors.forename: Gustav
authors.initials: G
authors.lastname: Schelling
mesh_terms: D002395:Catecholamines / Q000502:physiology*; D016638:Critical Illness; D063388:Endocannabinoids / Q000502:physiology*; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D008568:Memory / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*; D017741:Survivors
chemical_list: D002395:Catecholamines; D063388:Endocannabinoids; D005938:Glucocorticoids
keywords: Adrenergic drugs; Endocannabinoids; Glucocorticoids; Intensive care therapy; Post-traumatic stress disorder; Traumatic memory