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Influence of early stress on memory reconsolidation: Implications for post-traumatic stress disorder treatment.

ABSTRACT: Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a ?-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the "city-like" test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans.

SUBMITTER: Villain H

PROVIDER: S-EPMC5774817 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Influence of early stress on memory reconsolidation: Implications for post-traumatic stress disorder treatment.

Villain Hélène H Benkahoul Aïcha A Birmes Philippe P Ferry Barbara B Roullet Pascal P

PloS one 20180119 1

Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remi ...[more]

PMID: 29352277

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Project description:Post-traumatic stress disorder (PTSD) is a common mental disorder associated with significant distress and reduced functioning. Its occurrence after a severe traumatic event and association with characteristic neurobiological changes make PTSD a good candidate for pharmacological prevention and early treatment. The primary aim for this systematic review and meta-analysis was to assess whether pharmacological interventions when compared to placebo, or other pharmacological/psychosocial interventions resulted in a clinically significant reduction or prevention of symptoms, improved functioning or quality of life, presence of disorder, or adverse effects. A systematic search was undertaken to identify RCTs, which used early pharmacotherapy (within three months of a traumatic event) to prevent and treat PTSD and acute stress disorder (ASD) in children and adults. Using Cochrane Collaboration methodology, RCTs were identified and rated for risk of bias. Available data was pooled to calculate risk ratios (RR) for PTSD prevalence and standardised mean differences (SMD) for PTSD severity. 19 RCTs met the inclusion criteria; 16 studies with adult participants and three with children. The methodological quality of most trials was low. Only hydrocortisone in adults was found to be superior to placebo (3 studies, n = 88, RR: 0.21 (CI 0.05 to 0.89)) although this was in populations with severe physical illness, raising concerns about generalisability. No significant effects were found for the other pharmacotherapies investigated (propranolol, oxytocin, gabapentin, fish oil (1470 mg DHA/147 mg EPA), fish oil (224 mg DHA/22.4 mg EPA), dexamethasone, escitalopram, imipramine and chloral hydrate). Hydrocortisone shows the most promise, of pharmacotherapies subjected to RCTs, as an emerging intervention in the prevention of PTSD within three months after trauma and should be a target for further investigation. The limited evidence for hydrocortisone and its adverse effects mean it cannot be recommended for routine use, but, it could be considered as a preventative intervention for people with severe physical illness or injury, shortly after a traumatic event, as long as there are no contraindications. More research is needed using larger, high quality RCTs to establish the most efficacious use of hydrocortisone in different populations and optimal dosing, dosing window and route. There is currently a lack of evidence to suggest that other pharmacological agents are likely to be effective.

Project description:BackgroundPre-term or full-term childbirth can be experienced as physically or psychologically traumatic. Cumulative and trans-generational effects of traumatic stress on both psychological and physical health indicate the ethical requirement to investigate appropriate preventative treatment for stress symptoms in women following a routine traumatic experience such as childbirth.ObjectiveThe objective of this review was to investigate the effectiveness of early psychological interventions in reducing or preventing post-traumatic stress symptoms and post-traumatic stress disorder in post-partum women within twelve weeks of a traumatic birth.MethodsRandomised controlled trials and pilot studies of psychological interventions preventing or reducing post-traumatic stress symptoms or PTSD, that included women who had experienced a traumatic birth, were identified in a search of Cochrane Central Register of Randomised Controlled Trials, MEDLINE, Embase, Psychinfo, PILOTS, CINAHL and Proquest Dissertations databases. One author performed database searches, verified results with a subject librarian, extracted study details and data. Five authors appraised extracted data and agreed upon risk of bias. Analysis was completed with Rev Man 5 software and quality of findings were rated according to Grading of Recommendation, Assessment, Development, and Evaluation.ResultsEleven studies were identified that evaluated the effectiveness of a range of early psychological interventions. There was firm evidence to suggest that midwifery or clinician led early psychological interventions administered within 72 hours following traumatic childbirth are more effective than usual care in reducing traumatic stress symptoms in women at 4-6 weeks. Further studies of high methodological quality that include longer follow up of 6-12 months are required in order to substantiate the evidence of the effectiveness of specific face to face and online early psychological intervention modalities in preventing the effects of stress symptoms and PTSD in women following a traumatic birth before introduction to routine care and practice.Prospero registrationCRD42020202576, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=202576.

Dataset Information

Influence of early stress on memory reconsolidation: Implications for post-traumatic stress disorder treatment.

Publications

Influence of early stress on memory reconsolidation: Implications for post-traumatic stress disorder treatment.

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