Consolidation/reconsolidation therapies for the prevention and treatment of PTSD and re-experiencing: a systematic review and meta-analysis

Translational research highlights the potential of novel 'memory consolidation/reconsolidation therapies' to treat re-experiencing symptoms and post-traumatic stress disorder (PTSD). This systematic review and meta-analysis assessed the efficacy of so-called memory consolidation/reconsolidation therapies in randomised controlled trials (RCTs) for prevention and treatment of PTSD and symptoms of re-experiencing in children and adults (PROSPERO: CRD42020171167). 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/re-experiencing severity. Twenty-five RCTs met inclusion criteria (16 prevention and nine treatment trials). The methodology of most studies had a significant risk of bias. We found a large effect of reconsolidation interventions in the treatment of PTSD (11 studies, n = 372, SMD: −1.42 (−2.25 to −0.58), and a smaller positive effect of consolidation interventions in the prevention of PTSD (12 studies, n = 2821, RR: 0.67 (0.50 to 0.90). Only three protocols (hydrocortisone for PTSD prevention, Reconsolidation of Traumatic Memories (RTM) for treatment of PTSD symptoms and cognitive task memory interference procedure with memory reactivation (MR) for intrusive memories) were superior to control. There is some emerging evidence of consolidation and reconsolidation therapies in the prevention and treatment of PTSD and intrusive memories specifically. Translational research should strictly adhere to protocols/procedures describing precise reconsolidation conditions (e.g. MR) to both increase the likelihood of positive findings and more confidently interpret negative findings of putative reconsolidation agents

Statistics of electromagnetic transitions as a signature of chaos in many-electron atoms

Using a configuration interaction approach we study statistics of the dipole matrix elements (E1 amplitudes) between the 14 lower odd states with J=4 and 21st to 100th even states with J=4 in the Ce atom (1120 lines). We show that the distribution of the matrix elements is close to Gaussian, although the width of the Gaussian distribution, i.e. the root-mean-square matrix element, changes with the excitation energy. The corresponding line strengths are distributed according to the Porter-Thomas law which describes statistics of transition strengths between chaotic states in compound nuclei. We also show how to use a statistical theory to calculate mean squared values of the matrix elements or transition amplitudes between chaotic many-body states. We draw some support for our conclusions from the analysis of the 228 experimental line strengths in Ce [J. Opt. Soc. Am. v. 8, p. 1545 (1991)], although direct comparison with the calculations is impeded by incompleteness of the experimental data. Nevertheless, the statistics observed evidence that highly excited many-electron states in atoms are indeed chaotic.Comment: 16 pages, REVTEX, 4 PostScript figures (submitted to Phys Rev A

Comparative analysis of homology models of the Ah receptor ligand binding domain: Verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates the biological and toxic effects of a wide variety of structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While significant interspecies differences in AHR ligand binding specificity, selectivity, and response have been observed, the structural determinants responsible for those differences have not been determined, and homology models of the AHR ligand-binding domain (LBD) are available for only a few species. Here we describe the development and comparative analysis of homology models of the LBD of 16 AHRs from 12 mammalian and nonmammalian species and identify the specific residues contained within their ligand binding cavities. The ligand-binding cavity of the fish AHR exhibits differences from those of mammalian and avian AHRs, suggesting a slightly different TCDD binding mode. Comparison of the internal cavity in the LBD model of zebrafish (zf) AHR2, which binds TCDD with high affinity, to that of zfAHR1a, which does not bind TCDD, revealed that the latter has a dramatically shortened binding cavity due to the side chains of three residues (Tyr296, Thr386, and His388) that reduce the amount of internal space available to TCDD. Mutagenesis of two of these residues in zfAHR1a to those present in zfAHR2 (Y296H and T386A) restored the ability of zfAHR1a to bind TCDD and to exhibit TCDD-dependent binding to DNA. These results demonstrate the importance of these two amino acids and highlight the predictive potential of comparative analysis of homology models from diverse species. The availability of these AHR LBD homology models will facilitate in-depth comparative studies of AHR ligand binding and ligand-dependent AHR activation and provide a novel avenue for examining species-specific differences in AHR responsiveness. © 2013 American Chemical Society

The effect of the COVID-19 pandemic on mental health in individuals with pre-existing mental illness

BACKGROUND: There is evidence that the COVID-19 pandemic has negatively affected mental health, but most studies have been conducted in the general population. AIMS: To identify factors associated with mental health during the COVID-19 pandemic in individuals with pre-existing mental illness. METHOD: Participants (N = 2869, 78% women, ages 18–94 years) from a UK cohort (the National Centre for Mental Health) with a history of mental illness completed a cross-sectional online survey in June to August 2020. Mental health assessments were the GAD-7 (anxiety), PHQ-9 (depression) and WHO-5 (well-being) questionnaires, and a self-report question on whether their mental health had changed during the pandemic. Regressions examined associations between mental health outcomes and hypothesised risk factors. Secondary analyses examined associations between specific mental health diagnoses and mental health. RESULTS: A total of 60% of participants reported that mental health had worsened during the pandemic. Younger age, difficulty accessing mental health services, low income, income affected by COVID-19, worry about COVID-19, reduced sleep and increased alcohol/drug use were associated with increased depression and anxiety symptoms and reduced well-being. Feeling socially supported by friends/family/services was associated with better mental health and well-being. Participants with a history of anxiety, depression, post-traumatic stress disorder or eating disorder were more likely to report that mental health had worsened during the pandemic than individuals without a history of these diagnoses. CONCLUSIONS: We identified factors associated with worse mental health during the COVID-19 pandemic in individuals with pre-existing mental illness, in addition to specific groups potentially at elevated risk of poor mental health during the pandemic

Stress resilience during the coronavirus pandemic

The epidemic of the 2019 novel coronavirus SARS-CoV-2, causing the coronavirus disease 2019 (COVID-19) is a global public health emergency with multifaceted severe consequences for people's lives and their mental health. In this article, as members of the European College of Neuropsychopharmacology (ECNP) Resilience, we will discuss the urgent need for a focus on resilience during the current coronavirus pandemic. Resilience is pivotal to cope with stress and vital to stay in balance. We will discuss the importance of resilience at the individual and societal level, but also the implication for patients with a psychiatric condition and health care workers. We not only advocate for an increased focus on mental health during the coronavirus pandemic but also highlight the urgent need of augmenting our focus on resilience and on strategies to enhance it. The epidemic of the 2019 novel coronavirus SARS-CoV-2, causing the coronavirus disease 2019 (COVID-19), first expanded within the Wuhan region in China and quickly spread to Europe and to the rest of the world (Zhou et al., 2020). The outbreak of COVID-19 is a global public health emergency with multifaceted severe consequences for people's lives and their mental health. In this article, as members of the European College of Neuropsychopharmacology (ECNP) Resilience, we will discuss the urgent need for a focus on resilience during the current coronavirus pandemic. Resilience is pivotal to cope with stress and vital to stay in balance. We will discuss the importance of resilience at the individual and societal level, but also the implication for patients with a psychiatric condition and health care workers

The International Trauma Questionnaire: development of a self-report measure of ICD-11 PTSD and complex PTSD

Objective: The purpose of this study was to finalize the development of the International Trauma Questionnaire (ITQ); a self-report diagnostic measure of Posttraumatic Stress Disorder (PTSD) and Complex PTSD (CPTSD), as defined in the 11th version of the International Classification of Diseases (ICD-11).Method: The optimal symptom indicators of PTSD and CPTSD were identified by applying item response theory (IRT) analysis to data from a trauma-exposed community sample (n =1051) and a trauma-exposed clinical sample (n = 247) from the United Kingdom. The validity of the optimized 12-item ITQ was assessed with confirmatory factor analyses. Diagnostic rates were estimated and compared to previous validation studies.Results: The latent structure of the 12-item, optimized ITQ was consistent with prior findings, and diagnostic rates of PTSD and CPTSD were in line with previous estimates.Conclusion: The ITQ is a brief, simply-worded measure of the core features of PTSD and CPTSD. It is consistent with the organizing principles of the ICD-11 to maximize clinical utility and international applicability through a focus on a limited but central set of symptoms. The measure is freely available and can be found in the body of this paper

Emotional distress in cancer patients: the Edinburgh Cancer Centre symptom study

To: (1) estimate the prevalence of clinically significant emotional distress in patients attending a cancer outpatient department and (2) determine the associations between distress and demographic and clinical variables, we conducted a survey of outpatients attending selected clinics of a regional cancer centre in Edinburgh, UK. Patients completed the Hospital Anxiety and Depression Scale (HADS) on touch-screen computers and the scores were linked to clinical variables on the hospital database. Nearly one quarter of the cancer outpatients 674 out of 3071 (22%; 95% confidence interval (CI) 20–23%) met our criterion for clinically significant emotional distress (total HADS score 15 or more). Univariate analysis identified the following statistically significant associations: age <65, female gender, cancer type and extent of disease. Multivariate analysis indicated that age <65 (odds ratio 1.41; 95% CI 1.18–1.69), female gender (odds ratio 1.58; 95% CI 1.31–1.92) and active disease (odds ratio 1.72; 95% CI 1.43–2.05) but not cancer diagnosis, were the independent predictors of clinically significant emotional distress. Services to treat distress in cancer patients should be organised to target patients by characteristics other than their cancer diagnosis

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations