Interfering with the reconsolidation of traumatic memory: Sirolimus as a novel agent for treating veterans with posttraumatic stress disorder
VA North Texas Health Care System, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA. E-mail: . Annals of Clinical Psychiatry
(Impact Factor: 2.36).
Development of novel treatment approaches for combat-related posttraumatic stress disorder (PTSD) is critical, given the increasing prevalence of PTSD in veterans returning from war zone deployment. Established preclinical research using protein synthesis inhibitors (such as sirolimus) to interfere with fear memory reconsolidation provides a compelling rationale for investigation in humans.
This double-blind, placebo-controlled translational pilot study examined the effects of pairing reactivation of a trauma memory with a single administration of sirolimus on the frequency and intensity of PTSD symptoms in male combat veterans.
Primary analyses found no significant differences between treatment groups on any of the clinical or physiologic outcome measures. In an exploratory analysis of a subsample of post-Vietnam-era veterans who had more recent combat trauma, PTSD symptom scores fell significantly more in these veterans than in controls.
The post-Vietnam-era veteran findings suggest that further investigation of this pairing of sirolimus with traumatic memory reactivation may be warranted. Theoretically, interference with the reconsolidation of fear memories could ameliorate military-related psychological trauma symptoms. Future research should focus on veterans of more recent eras whose traumatic memories may be less entrenched and more amenable to pharmacologic modification within this procedure.
Available from: Carol North
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ABSTRACT: Exposure to a disaster is common, and one-third or more of individuals severely exposed may develop posttraumatic stress disorder or other disorders. A systematic approach to the delivery of timely and appropriate disaster mental health services may facilitate their integration into the emergency medical response.
To review and summarize the evidence for how best to identify individuals in need of disaster mental health services and triage them to appropriate care.
Search of the peer-reviewed English-language literature on disaster mental health response in PsycINFO, PubMed, Cochrane Database of Systematic Reviews, Academic Search Complete, and Google Scholar (inception to September 2012) and PILOTS (inception to February 2013), using a combination of subject headings and text words (Disasters, Natural Disasters, Mental Health, Mental Health Programs, Public Health Services, Mental Disorders, Mental Health Services, Community Mental Health Services, Emergency Services Psychiatric, Emotional Trauma, Triage, and Response).
Unlike physical injuries, adverse mental health outcomes of disasters may not be apparent, and therefore a systematic approach to case identification and triage to appropriate interventions is required. Symptomatic individuals in postdisaster settings may experience new-onset disaster-related psychiatric disorders, exacerbations of preexisting psychopathology, and/or psychological distress. Descriptive disaster mental health studies have found that many (11%-38%) distressed individuals presenting for evaluation at shelters and family assistance centers have stress-related and adjustment disorders; bereavement, major depression, and substance use disorders were also observed, and up to 40% of distressed individuals had preexisting disorders. Individuals with more intense reactions to disaster stress were more likely to accept referral to mental health services than those with less intense reactions. Evidence-based treatments are available for patients with active psychiatric disorders, but psychosocial interventions such as psychological first aid, psychological debriefing, crisis counseling, and psychoeducation for individuals with distress have not been sufficiently evaluated to establish their benefit or harm in disaster settings.
In postdisaster settings, a systematic framework of case identification, triage, and mental health interventions should be integrated into emergency medicine and trauma care responses.
JAMA The Journal of the American Medical Association 08/2013; 310(5):507-18. DOI:10.1001/jama.2013.107799 · 35.29 Impact Factor
Available from: Eric Vermetten
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ABSTRACT: Several lines of research have demonstrated that memories for fearful events become transiently labile upon re-exposure. Activation of molecular mechanisms is required in order to maintain retrieved information. This process is called reconsolidation. Targeting reconsolidation - as in exposure-based psychotherapy - offers therefore a potentially interesting tool to manipulate fear memories, and subsequently to treat disorders such as post-traumatic stress disorder (PTSD). In this paper we discuss the evidence for reconsolidation in rodents and humans and highlight recent studies in which clinical research on normal and abnormal fear extinction reduction of the expression of fear was obtained by targeting the process of reconsolidation. We conclude that reconsolidation presents an interesting opportunity to modify or alter fear and fear-related memories. More clinical research on normal and abnormal fear extinction is required.
Current Psychiatry Reports 07/2014; 16(7):455. DOI:10.1007/s11920-014-0455-y · 3.24 Impact Factor
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ABSTRACT: Fear memory is a motivational system essential for organisms survival having a central role in organization of defensive behaviors to threat. In the last years there has been a growing interest on conditioned fear memory reconsolidation and extinction, two specific phases of memorization process, both induced by memory retrieval. Understanding the mechanisms underlying these two mnemonic processes may allow to work out therapeutic interventions for treatment of human fear and anxiety disorders, such as specific phobias and post-traumatic stress disorder. Based on the use of one-trial conditioning paradigms, which allow to follow the evolution of a mnemonic trace in its various phases, the present paper has attempted to reorganize the current literature relative to the rodents highlighting both the role of several brain structures in conditioned fear memory reconsolidation and extinction and the selective cellular processes involved. A crucial role seems to be play by medial prefrontal cortex, in particular by prelimbic and infralimbic cortices, and by distinct connections between them and the amygdala, hippocampus and entorhinal cortex.
Copyright © 2015. Published by Elsevier Ltd.
Neuroscience & Biobehavioral Reviews 04/2015; 53. DOI:10.1016/j.neubiorev.2015.04.003 · 8.80 Impact Factor
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