PTSD treatment in times of COVID-19:A systematic review of the effects of online EMDR

COVID-19 affects many societies by measures as “social distancing”, forcing mental health care professionals to deliver treatments online or via telephone. In this context, online Eye Movement Desensitization and Reprocessing (EMDR) is an emerging treatment for patients with Posttraumatic Stress Disorder (PTSD). We performed a systematic review of studies investigating online EMDR for PTSD. Only one trial was identified. That uncontrolled open trial showed promising results. There is an urgent need to further examine the effects of online EMDR for PTSD, before its wider dissemination is warranted. Remotely delivered cognitive behavioural therapy seems the preferred PTSD-treatment in times of COVID-19

Online treatment of persistent complex bereavement disorder, posttraumatic stress disorder, and depression symptoms in people who lost loved ones during the COVID-19 pandemic:study protocol for a randomized controlled trial and a controlled trial

Background: Losing a loved one during the COVID-19 pandemic is a potentially traumatic loss that may result in symptoms of persistent complex bereavement disorder (PCBD), posttraumatic stress disorder (PTSD), and depression. To date, grief-specific cognitive-behavioural therapy (CBT) has mostly been delivered through individual face-to-face formats, while studies have shown that online treatment also yields promising results. Offering treatment online is now more than ever relevant during the pan demic and may offer important benefits compared with face-to-face CBT, such as lower costs and higher accessibility. Our expectation is that grief-specific online CBT is effective in reducing PCBD, PTSD, and depression symptoms. Objective: Our aim is to evaluate the short-term and long-term effectiveness of grief-specific online CBT in reducing PCBD, PTSD, and depression symptom-levels for adults who lost a loved one during the COVID-19 pandemic. Method: This study consists of two parts. In part 1, a two-armed (unguided online CBT versus waitlist controls) randomized controlled trial will be conducted. In part 2, a two-armed (guided online CBT versus unguided online CBT) controlled trial will be conducted. Symptoms of PCBD, PTSD, and depression will be assessed via telephone interviews at pre-treatment/pre-waiting period, post-treatment/post-waiting period, and six months post-treatment. Potential participants are people who lost a loved one at least three months earlier during the COVID-19 pandemic with clinically relevant levels of PCBD, PTSD, and/or depression. Analysis of covariance and multilevel modelling will be performed. Discussion: This is one of the first studies examining the effectiveness of online grief-specific CBT. More research is needed before implementing online grief-specific CBT into clinical practice

EGFR/HER2 inhibitor AEE788 increases ER-mediated transcription in HER2/ER-positive breast cancer cells but functions synergistically with endocrine therapy

BACKGROUND: Cross-talk between receptor tyrosine kinases and the oestrogen receptor (ER) is implicated in resistance to endocrine therapy. We investigated whether AEE788 (a combined inhibitor of EGFR, HER2 and VEGFR) plus tamoxifen or letrozole enhanced the individual anti-tumour effects of these agents. METHODS: Breast cancer cell lines modelling endocrine-resistant and -sensitive disease were engineered to express aromatase (A) and examined using proliferation, western blotting and ER-alpha transcription assays. RESULTS: AEE788 enhanced the anti-proliferative effect of tamoxifen and letrozole in ER+ cell lines (MCF-7 2A, ZR75.1 A3 and BT474 A3). This associated with an elevated G1 arrest and nuclear accumulation of p27. It is noteworthy that AEE788 alone or in combination with endocrine therapy increased the expression of progesterone receptor (PGR) and TFF1 in BT474 A3 cells. This may indicate a mechanism of resistance to AEE788 in ER+/HER2(+) breast cancers. In a ZR75.1 A3 xenograft, AEE788 alone or in combination with tamoxifen provided no further benefit compared with letrozole. However, letrozole plus AEE788 produced a significantly greater inhibition of tumour growth compared with letrozole alone. CONCLUSION: These data suggest that AEE788 plus letrozole in breast cancer overexpressing HER2 may provide superior anti-tumour activity, compared with single agents. British Journal of Cancer (2010) 102, 1235-1243. doi: 10.1038/sj.bjc.6605641 www.bjcancer.com (C) 2010 Cancer Research U

The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells

INTRODUCTION: Loss of the cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in breast cancer. The decrease in p27 levels is mainly the result of enhanced proteasome-dependent degradation mediated by its specific ubiquitin ligase subunit S phase kinase protein 2 (Skp2). The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer. Rapamycin was found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 expression is unknown. METHODS: The expression of Skp2 mRNA and protein levels were examined in rapamycin-treated breast cancer cell lines. The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1. RESULTS: Rapamycin significantly decreased Skp2 mRNA and protein levels in a dose and time-dependent fashion, depending on the sensitivity of the cell line to rapamycin. The decrease in Skp2 levels in the different cell lines was followed by cell growth arrest at G1. In addition, rapamycin enhanced the degradation rate of Skp2 and down-regulated the expression of the APC\C inhibitor Emi1. CONCLUSION: These results suggest that Skp2, an important oncogene in the development and progression of breast cancer, may be a novel target for rapamycin treatment

Psycho-social factors associated with mental resilience in the Corona lockdown

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics