Epigenetic Modification of the Glucocorticoid Receptor Gene Is Linked to Traumatic Memory and Post-Traumatic Stress Disorder Risk in Genocide Survivors

Intrusive and distressing memories are at the core of post-traumatic stress disorder (PTSD). Since cardiorespiratory fitness (CRF) has been linked with improved mental health, emotion regulation, and memory function, CRF may, by promoting these capabilities, protect against the development of intrusions after trauma. We investigated this idea in 115 healthy individuals, using a trauma film to induce intrusions. As potential mediators, we assessed indices of pre-trauma mental health such as heart rate variability, subjective and psychobiological peri-traumatic responses, and memory. Critically, results showed that higher CRF was related to fewer intrusions, but no mediators emerged of the CRF-intrusion relationship. These results indicate that individuals displaying higher CRF are less prone to develop traumatic memory intrusions. This suggests that promoting fitness prior to possible trauma exposure may provide a useful strategy to boost resilience against the development of debilitating re-experiencing symptoms of PTSD.

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Electroconvulsive Therapy with a Memory Reactivation Intervention for Post-Traumatic Stress Disorder: A Randomized Controlled Trial

10.1101/2020.10.10.20210450 ◽

2020 ◽

Author(s):

Victor M. Tang ◽

Kathleen Trought ◽

Kristina M. Gicas ◽

Mari Kozak ◽

Sheena A. Josselyn ◽

...

Keyword(s):

Heart Rate ◽

Electroconvulsive Therapy ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Traumatic Memory ◽

Post Traumatic Stress ◽

Memory Reactivation ◽

Link Type ◽

Post Traumatic

AbstractIntroductionPost-traumatic Stress Disorder (PTSD) often does not respond to available treatments. Memories are vulnerable to disruption during reconsolidation, and electroconvulsive therapy (ECT) has amnestic effects. We sought to exploit this phenomenon as a potential treatment for PTSD with a clinical trial of patients with PTSD receiving ECT.MethodsTwenty-eight participants with severe depression with comorbid PTSD referred for ECT treatment were randomly assigned to reactivation of a traumatic or non-traumatic memory using script driven imagery prior to each ECT treatment. Primary outcomes were change in scores on the Modified PTSD Symptom Scale - Self Report (MPSS-SR) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Assessments were completed by blinded raters. Secondary outcomes included a comparison of the change in heart rate while listening to the script.ResultsTwenty-five patients who completed a post-ECT assessment were included in the analysis. No significant group differences were found in the MPSS-SR or CAPS-5 scores from pre-ECT to post-ECT or 3-month follow-ups. However, both groups improved at post-ECT and 3-month follow up. Partial eta squared estimates of effect size showed large effect sizes for all outcomes (η2 > 0.13). Changes in heart rate were not significantly different between groups or over time.ConclusionsIn this RCT, ECT paired with pre-treatment traumatic memory reactivation was not more effective for treating PTSD symptoms than ECT alone. While our primary hypothesis was not supported, our data provides further support for the efficacy of ECT for improving symptoms of PTSD with comorbid depression.ClinicalTrials.govhttps://clinicaltrials.gov/ct2/show/NCT04027452Identifier: NCT04027452

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Leukocyte glucocorticoid receptor expression and immunoregulation in veterans with and without post-traumatic stress disorder

Molecular Psychiatry ◽

10.1038/sj.mp.4001934 ◽

2007 ◽

Vol 12 (5) ◽

pp. 443-453 ◽

Cited By ~ 72

Author(s):

C S de Kloet ◽

E Vermetten ◽

A Bikker ◽

E Meulman ◽

E Geuze ◽

...

Keyword(s):

Glucocorticoid Receptor ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Receptor Expression ◽

Post Traumatic Stress ◽

Post Traumatic

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Flow cytometric determination of glucocorticoid receptor (GCR) expression in lymphocyte subpopulations: lower quantity of GCR in patients with post-traumatic stress disorder (PTSD)

Clinical & Experimental Immunology ◽

10.1046/j.1365-2249.2003.02075.x ◽

2003 ◽

Vol 131 (2) ◽

pp. 335-339 ◽

Cited By ~ 69

Author(s):

K. GOTOVAC ◽

A. SABIONCELLO ◽

S. RABATI´C ◽

T. BERKI ◽

D. DEKARIS

Keyword(s):

Glucocorticoid Receptor ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Lymphocyte Subpopulations ◽

Post Traumatic Stress ◽

Flow Cytometric ◽

Lower Quantity ◽

Post Traumatic

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Glucocorticoid-related predictors and correlates of post-traumatic stress disorder treatment response in combat veterans

Interface Focus ◽

10.1098/rsfs.2014.0048 ◽

2014 ◽

Vol 4 (5) ◽

pp. 20140048 ◽

Cited By ~ 60

Author(s):

Rachel Yehuda ◽

Laura C. Pratchett ◽

Matthew W. Elmes ◽

Amy Lehrner ◽

Nikolaos P. Daskalakis ◽

...

Keyword(s):

Treatment Response ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Prolonged Exposure ◽

Clinical State ◽

Post Traumatic Stress ◽

Glucocorticoid Receptor Gene ◽

Significant Difference ◽

Post Traumatic

The identification of biomarkers for post-traumatic stress disorder (PTSD) and resilience/recovery is critical for advancing knowledge about pathophysiology and treatment in trauma-exposed persons. This study examined a series of glucocorticoid-related biomarkers prior to and in response to psychotherapy. Fifty-two male and female veterans with PTSD were randomized 2 : 1 to receive either prolonged exposure (PE) therapy or a weekly minimal attention (MA) intervention for 12 consecutive weeks. Psychological and biological assessments were obtained prior to and following treatment and after a 12-week naturalistic follow-up. Response was defined dichotomously as no longer meeting criteria for PTSD at post-treatment based on the Clinician Administered PTSD Scale for DSM-IV (CAPS). Clinical improvement on the CAPS was apparent for both PE and MA, with no significant difference according to treatment condition. Biomarkers predictive of treatment gains included the BCLI polymorphism of the glucocorticoid receptor gene. Additional predictors of treatment response were higher bedtime salivary cortisol and 24 h urinary cortisol excretion. Pre-treatment plasma dehydroepiandrosterone/cortisol ratio and neuropetide Y (NPY) levels were predictors of reductions in PTSD symptoms, and, for NPY only, of other secondary outcomes as well, including anxiety and depression ratings. Glucocorticoid sensitivity changed in association with symptom change, reflecting clinical state. It is possible to distinguish prognostic and state biomarkers of PTSD using a longitudinal approach in the context of treatment. Identified markers may also be relevant to understanding mechanisms of action of symptom reduction.

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