EMDR v. other psychological therapies for PTSD: a systematic review and individual participant data meta-analysis.

BACKGROUND: This systematic review and individual participant data meta-analysis (IPDMA) examined the overall effectiveness of eye movement desensitization and reprocessing (EMDR) in reducing posttraumatic stress disorder (PTSD) symptoms, achieving response and remission, and reducing treatment dropout among adults with PTSD compared to other psychological treatments. Additionally, we examined available participant-level moderators of the efficacy of EMDR. METHODS: This study included randomized controlled trials. Eligible studies were identified by a systematic search in PubMed, Embase, PsyclNFO, PTSDpubs, and CENTRAL. The target population was adults with above-threshold baseline PTSD symptoms. Trials were eligible if at least 70% of study participants had been diagnosed with PTSD using a structured clinical interview. Primary outcomes included PTSD symptom severity, treatment response, and PTSD remission. Treatment dropout was a secondary outcome. The systematic search retrieved 15 eligible randomized controlled trials (RCTs); 8 of these 15 were able to be included in this IPDMA (346 patients). Comparator treatments included relaxation therapy, emotional freedom technique, trauma-focused cognitive behavioral psychotherapies, and REM-desensitization. RESULTS: One-stage IPDMA found no significant difference between EMDR and other psychological treatments in reducing PTSD symptom severity (ß = -0.24), achieving response (ß = 0.86), attaining remission (ß = 1.05), or reducing treatment dropout rates (ß = -0.25). Moderator analyses found unemployed participants receiving EMDR had higher PTSD symptom severity at the post-test, and males were more likely to drop out of EMDR treatment than females. CONCLUSION: The current study found no significant difference between EMDR and other psychological treatments. We found some indication of the moderating effects of gender and employment status.

The associations of hair cortisol and DHEA with posttraumatic stress disorder symptoms in refugees.

BACKGROUND: Exposure to traumatic events, ongoing adversity, and posttraumatic stress disorder (PTSD) are associated with altered activity of the hypothalamic-pituitary-adrenal (HPA) axis, but findings are mixed. This may be explained in part by heterogeneity in PTSD symptom profiles. AIM: The aim of this study was to investigate the complex relationships between the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and dehydroepiandrosterone (DHEA) in refugees. METHODS: Adult (18+ years) Syrian refugees with increased levels of distress participating in a randomized controlled trial completed baseline measures to assess traumatic events (trauma checklist), post-displacement stressors (Post-Migration Living Difficulties checklist), symptoms of PTSD (PTSD Checklist for DSM-5; PCL-5), and provided a hair sample for additional stress hormone analyses. We used R-packages qgraph and bootnet to perform network analysis on the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and DHEA. The final network model was corrected for depression severity. RESULTS: 115 (53% male, M age = 36.9, SD = 12.7) of 206 participants provided a hair sample. A higher number of traumatic events was directly associated with three symptoms of the PTSD cluster arousal and reactivity, i.e., sleep disturbance, hypervigilance and physiological reactivity, and with three other PTSD symptoms, namely flashbacks, avoidance of reminders, and self-destructive behavior. A higher number of post-displacement stressors was associated with four symptoms of the PTSD cluster cognition and mood, i.e., trauma-related amnesia, negative beliefs, blaming of self/others, and detachment, as well as with intrusive thoughts, sleep disturbance, hypervigilance, and exaggerated startle response. The number of traumatic events and post-displacement stressors were not associated with cortisol or DHEA. Cortisol was positively associated with two symptoms of the PTSD cluster cognition and mood, i.e., negative beliefs and negative trauma-related emotions, and negatively associated with avoidance of reminders. DHEA was positively associated with restricted affect and with three symptoms of the PTSD symptom cluster arousal and reactivity, i.e., irritability/anger, sleep disturbance, and self-destructive behavior, and negatively associated with avoidance of thoughts. CONCLUSIONS: This study demonstrated that exposure to traumatic events and post-displacement stressors is not related to cortisol and DHEA, but that cortisol and DHEA are differentially related to individual symptoms of PTSD. While lower levels of both cortisol and DHEA were associated with increased avoidance, higher levels of cortisol were mostly associated with symptoms of the PTSD cluster cognition and mood and higher levels of DHEA were mostly associated with symptoms of the PTSD cluster arousal and reactivity. These findings contribute to explaining the variability of findings in the literature on HPA-axis activity in PTSD. ETHICS: The study was approved by the Research Ethics Review Committee at VU Medical Center, the Netherlands (Protocol ID: NL61361.029.17, 7 September 2017) and prospectively registered online (https://www.trialregister.nl/trial/6665).

COVID-19 and common mental health symptoms in the early phase of the pandemic: An umbrella review of the evidence.

BACKGROUND: There remains uncertainty about the impact of the Coronavirus Disease 2019 (COVID-19) pandemic on mental health. This umbrella review provides a comprehensive overview of the association between the pandemic and common mental disorders. We qualitatively summarized evidence from reviews with meta-analyses of individual study-data in the general population, healthcare workers, and specific at-risk populations. METHODS AND FINDINGS: A systematic search was carried out in 5 databases for peer-reviewed systematic reviews with meta-analyses of prevalence of depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms during the pandemic published between December 31, 2019 until August 12, 2022. We identified 123 reviews of which 7 provided standardized mean differences (SMDs) either from longitudinal pre- to during pandemic study-data or from cross-sectional study-data compared to matched pre-pandemic data. Methodological quality rated with the Assessment of Multiple Systematic Reviews checklist scores (AMSTAR 2) instrument was generally low to moderate. Small but significant increases of depression, anxiety, and/or general mental health symptoms were reported in the general population, in people with preexisting physical health conditions, and in children (3 reviews; SMDs ranged from 0.11 to 0.28). Mental health and depression symptoms significantly increased during periods of social restrictions (1 review; SMDs of 0.41 and 0.83, respectively) but anxiety symptoms did not (SMD: 0.26). Increases of depression symptoms were generally larger and longer-lasting during the pandemic (3 reviews; SMDs depression ranged from 0.16 to 0.23) than those of anxiety (2 reviews: SMDs 0.12 and 0.18). Females showed a significantly larger increase in anxiety symptoms than males (1 review: SMD 0.15). In healthcare workers, people with preexisting mental disorders, any patient group, children and adolescents, and in students, no significant differences from pre- to during pandemic were found (2 reviews; SMD's ranging from -0.16 to 0.48). In 116 reviews pooled cross-sectional prevalence rates of depression, anxiety, and PTSD symptoms ranged from 9% to 48% across populations. Although heterogeneity between studies was high and largely unexplained, assessment tools and cut-offs used, age, sex or gender, and COVID-19 exposure factors were found to be moderators in some reviews. The major limitations are the inability to quantify and explain the high heterogeneity across reviews included and the shortage of within-person data from multiple longitudinal studies. CONCLUSIONS: A small but consistent deterioration of mental health and particularly depression during early pandemic and during social restrictions has been found in the general population and in people with chronic somatic disorders. Also, associations between mental health and the pandemic were stronger in females and younger age groups than in others. Explanatory individual-level, COVID-19 exposure, and time-course factors were scarce and showed inconsistencies across reviews. For policy and research, repeated assessments of mental health in population panels including vulnerable individuals are recommended to respond to current and future health crises.

Coping with COVID: risk and resilience factors for mental health in a German representative panel study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare. METHODS: In a stratified random sample of the German household population (n = 6684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress [(PD; measured via Patient Health Questionnaire for Depression and Anxiety (PHQ-4)] from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting. RESULTS: PHQ-4 scores in 2020 (M = 2.45) and 2021 (M = 2.21) were elevated compared to 2019 (M = 1.79). Several risk factors (catastrophizing, neuroticism, and asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, and optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes. CONCLUSIONS: We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. A comparison of pre-pandemic data stresses the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.

Commentary: Promoting positive mental health during pregnancy-reflections on Lähdepuro et al. (2023).

Lähdepuro et al. performed a sound large-scale prospective pregnancy cohort study showing an association between positive maternal prenatal mental health and a reduced risk of developing clinically diagnosed childhood mental and behavioral disorders. Beneficial effects were also observed among the offspring of mothers experiencing mental health problems before and during pregnancy. The pathbreaking findings of Lähdepuro et al. set the stage for future research to shed more light on the so far almost unknown (neuro)biological mechanisms underlying the link between positive maternal prenatal mental health and child outcomes. More knowledge is needed about prenatal psychological and social factors enacting the potential of positive mental health as a resilience source buffering against maternal prenatal mental health problems and by this protecting subsequent child development. This also calls for further development, optimization, and evaluation of positive mental health-enhancing interventions during pregnancy, especially for future mothers having mental health problems.

Risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 mortality in people with pre-existing mental disorders: an umbrella review.

INTRODUCTION: The COVID-19 pandemic has posed a serious health risk, especially in vulnerable populations. Even before the pandemic, people with mental disorders had worse physical health outcomes compared to the general population. This umbrella review investigated whether having a pre-pandemic mental disorder was associated with worse physical health outcomes due to the COVID-19 pandemic. METHODS: Following a pre-registered protocol available on the Open Science Framework platform, we searched Ovid MEDLINE All, Embase (Ovid), PsycINFO (Ovid), CINAHL, and Web of Science up to the 6th of October 2021 for systematic reviews on the impact of COVID-19 on people with pre-existing mental disorders. The following outcomes were considered: risk of contracting the SARS-CoV-2 infection, risk of severe illness, COVID-19 related mortality risk, risk of long-term physical symptoms after COVID-19. For meta-analyses, we considered adjusted odds ratio (OR) as effect size measure. Screening, data extraction and quality assessment with the AMSTAR 2 tool have been done in parallel and duplicate. RESULTS: We included five meta-analyses and four narrative reviews. The meta-analyses reported that people with any mental disorder had an increased risk of SARS-CoV-2 infection (OR: 1.71, 95% CI 1.09-2.69), severe illness course (OR from 1.32 to 1.77, 95%CI between 1.19-1.46 and 1.29-2.42, respectively) and COVID-19 related mortality (OR from 1.38 to 1.52, 95%CI between 1.15-1.65 and 1.20-1.93, respectively) as compared to the general population. People with anxiety disorders had an increased risk of SAR-CoV-2 infection, but not increased mortality. People with mood and schizophrenia spectrum disorders had an increased COVID-19 related mortality but without evidence of increased risk of severe COVID-19 illness. Narrative reviews were consistent with findings from the meta-analyses. DISCUSSION AND CONCLUSIONS: As compared to the general population, there is strong evidence showing that people with pre-existing mental disorders suffered from worse physical health outcomes due to the COVID-19 pandemic and may therefore be considered a risk group similar to people with underlying physical conditions. Factors likely involved include living accommodations with barriers to social distancing, cardiovascular comorbidities, psychotropic medications and difficulties in accessing high-intensity medical care.

Effectiveness of a scalable, remotely delivered stepped-care intervention to reduce symptoms of psychological distress among Polish migrant workers in the Netherlands: study protocol for the RESPOND randomised controlled trial.

BACKGROUND: The COVID-19 pandemic has negatively affected the mental health of international migrant workers (IMWs). IMWs experience multiple barriers to accessing mental health care. Two scalable interventions developed by the World Health Organization (WHO) were adapted to address some of these barriers: Doing What Matters in times of stress (DWM), a guided self-help web application, and Problem Management Plus (PM +), a brief facilitator-led program to enhance coping skills. This study examines whether DWM and PM + remotely delivered as a stepped-care programme (DWM/PM +) is effective and cost-effective in reducing psychological distress, among Polish migrant workers with psychological distress living in the Netherlands. METHODS: The stepped-care DWM/PM + intervention will be tested in a two-arm, parallel-group, randomized controlled trial (RCT) among adult Polish migrant workers with self-reported psychological distress (Kessler Psychological Distress Scale; K10 > 15.9). Participants (n = 212) will be randomized into either the intervention group that receives DWM/PM + with psychological first aid (PFA) and care-as-usual (enhanced care-as-usual or eCAU), or into the control group that receives PFA and eCAU-only (1:1 allocation ratio). Baseline, 1-week post-DWM (week 7), 1-week post-PM + (week 13), and follow-up (week 21) self-reported assessments will be conducted. The primary outcome is psychological distress, assessed with the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS). Secondary outcomes are self-reported symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), resilience, quality of life, and cost-effectiveness. In a process evaluation, stakeholders' views on barriers and facilitators to the implementation of DWM/PM + will be evaluated. DISCUSSION: To our knowledge, this is one of the first RCTs that combines two scalable, psychosocial WHO interventions into a stepped-care programme for migrant populations. If proven to be effective, this may bridge the mental health treatment gap IMWs experience. TRIAL REGISTRATION: Dutch trial register NL9630, 20/07/2021, https://www.onderzoekmetmensen.nl/en/trial/27052.

Are we equally at risk of changing smoking behavior during a public health crisis? Impact of educational level on smoking from the TEMPO cohort.

BACKGROUND: The COVID-19 pandemic as a public health crisis has led to a significant increase in mental health difficulties. Smoking is strongly associated with mental health conditions, which is why the pandemic might have influenced the otherwise decline in smoking rates. Persons belonging to socioeconomically disadvantaged groups may be particularly affected, both because the pandemic has exacerbated existing social inequalities and because this group was more likely to smoke before the pandemic. We examined smoking prevalence in a French cohort study, focusing on differences between educational attainment. In addition, we examined the association between interpersonal changes in tobacco consumption and educational level from 2018 to 2021. METHODS: Using four assessments of smoking status available from 2009 to 2021, we estimated smoking prevalence over time, stratified by highest educational level in the TEMPO cohort and the difference was tested using chi2 test. We studied the association between interpersonal change in smoking status between 2018 and 2021 and educational attainment among 148 smokers, using multinomial logistic regression. RESULTS: Smoking prevalence was higher among those with low education. The difference between the two groups increased from 2020 to 2021 (4.8-9.4%, p < 0.001). Smokers with high educational level were more likely to decrease their tobacco consumption from 2018 to 2021 compared to low educated smokers (aOR = 2.72 [1.26;5.89]). CONCLUSION: Current findings showed a widening of the social inequality gap in relation to smoking rates, underscoring the increased vulnerability of persons with low educational level to smoking and the likely inadequate focus on social inequalities in relation to tobacco control policies during the pandemic.

Addressing mental health problems among persons without stable housing in the context of the COVID-19 pandemic: study protocol for a randomised trial. RESPOND - France.

BACKGROUND: The COVID-19 pandemic has had an impact on population-wide mental health and well-being. Although people experiencing socioeconomic disadvantage may be especially vulnerable, they experience barriers in accessing mental health care. To overcome these barriers, the World Health Organization (WHO) designed two scalable psychosocial interventions, namely the web-based Doing What Matters in Times of Stress (DWM) and the face-to-face Problem Management Plus (PM+), to help people manage stressful situations. Our study aims to test the effectiveness of a stepped-care program using DWM and PM + among individuals experiencing unstable housing in France - a majority of whom are migrant or have sought asylum. METHODS: This is a randomised controlled trial to evaluate the effectiveness and cost effectiveness of a stepped-care program using DWM and PM + among persons with psychological distress and experiencing unstable housing, in comparison to enhanced care as usual (eCAU). Participants (N = 210) will be randomised to two parallel groups: eCAU or eCAU plus the stepped-care program. The main study outcomes are symptoms of depression and anxiety measured using the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS). DISCUSSION: This randomised controlled trial will contribute to a better understanding of effective community-based scalable strategies that can help address the mental health needs of persons experiencing socioeconomic disadvantage, whose needs are high yet who frequently have limited access to mental health care services. TRIAL REGISTRATION: this randomised trial has been registered at ClinicalTrials.gov under the number NCT05033210.

The effect of offering a third-trimester routine ultrasound on pregnancy-specific anxiety and mother-to-infant bonding in low-risk women: A pragmatic cluster-randomized controlled trial.

BACKGROUND: Third-trimester routine ultrasounds are increasingly offered to monitor fetal growth. In addition to limited evidence for its clinical effectiveness, little is known about its importance for pregnancy-specific anxiety and mother-to-infant bonding. METHODS: 1275 low-risk women participated in a Dutch nationwide pragmatic cluster-randomized trial and answered questionnaires on pregnancy-specific anxiety (PRAQ-R) and prenatal mother-to-infant bonding (MAAS) before and after a third-trimester routine ultrasound was offered to the intervention group. Linear mixed model regression analyses were performed to examine the effect of offering a third-trimester routine ultrasound on pregnancy-specific anxiety and mother-to-infant bonding. In addition, we examined whether the effect depended on maternal background characteristics and level of satisfaction with the ultrasound procedure. RESULTS: We found no effect of offering a third-trimester routine ultrasound on pregnancy-specific anxiety and mother-to-infant bonding. However, interaction analyses showed that women with high levels of depressive symptoms at baseline and women who were very satisfied with the ultrasound procedure benefited somewhat more from offering a third-trimester routine ultrasound in terms of mother-to-infant bonding compared with women with low or no depressive symptoms, or less satisfied women. CONCLUSIONS: The relationship between offering a third-trimester routine ultrasound with pregnancy-specific anxiety and mother-to-infant bonding is limited. A beneficial effect only applies to some subgroups of women. This implies that, in terms of psychological outcomes, there are no counterarguments to implementing a third-trimester routine ultrasound. Strong evidence for offering all pregnant women a third-trimester routine ultrasound for psychological reasons, however, is lacking.

Psychosocial and peripartum determinants of postpartum depression: Findings from a prospective population-based cohort. The ABCD study.

BACKGROUND: Postpartum depression is prevalent and concerns a serious health problem for women and their families. The current large-scale birth cohort study investigated: (1) the associations of various potential determinants of postpartum depression using a multidimensional approach, and (2) the individual contribution of obstetric and perinatal determinants and pregnancy-specific anxiety to the risk of postpartum depression. METHODS: This study was based on a large-scale birth cohort study in Amsterdam, the Netherlands (ABCD-study). In 5109 women depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (cut-off ≥16 indicating high risk of postpartum depression). Determinants were assessed using self-report or perinatal registries. RESULTS: In the final multivariable model, other-Western and non-Western ethnic background, increased antepartum depressive symptoms, increased antepartum anxiety, increased pregnancy-specific anxiety, being unemployed, poor sleep quality, unwanted pregnancy, abuse, multiparity, and congenital abnormality were all independently related to an increased risk of postpartum depression. The strongest risk factors for postpartum depression were antepartum depressive symptoms (adjusted odds ratio (AOR) = 3.86, 95% confidence interval (CI) 3.02-4.92), having a baby with a congenital abnormality (AOR = 2.33, 95% CI 1.46-3.73), and abuse (AOR = 1.95, 95% CI 1.02-3.73). The final model accounted for 24.5% of the variance. LIMITATIONS: Our dataset did not provide information on social support or maternal and family history of depression. Next to these determinants, future research should include biological factors. CONCLUSIONS: The determinants identified provide opportunities for the development of multidimensional early screening and early intervention strategies for women with an increased risk of postpartum depression.

Effectiveness of a guided ACT-based self-help resilience training for depressive symptoms during pregnancy: Study protocol of a randomized controlled trial embedded in a prospective cohort.

BACKGROUND: During pregnancy, about 10 to 20% of women experience depressive symptoms. Subclinical depression increases the risk of peripartum depression, maternal neuro-endocrine dysregulations, and adverse birth and infant outcomes. Current treatments often comprise face-to-face psychological or pharmacological treatments that may be too intensive for women with subclinical depression leading to drop-out and moderate effectiveness. Therefore, easily accessible, resilience enhancing and less stigmatizing interventions are needed to prevent the development of clinical depression. This paper describes the protocol of a prospective cohort study with an embedded randomized controlled trial (RCT) that aims to improve mental resilience in a sample of pregnant women through a self-help program based on the principles of Acceptance and Commitment Therapy (ACT). Maternal and offspring correlates of the trajectories of peripartum depressive symptoms will also be studied. METHODS: Pregnant women (≥ 18 years) receiving care in Dutch midwifery practices will participate in a prospective cohort study (n ~ 3500). Between 12 and 18 weeks of pregnancy, all women will be screened for depression with the Edinburgh Postnatal Depression Scale (EPDS). Women with an EPDS score ≥ 11 will be evaluated with a structured clinical interview. Participants with subclinical depression (n = 290) will be randomized to a 9-week guided self-help ACT-training or to care as usual (CAU). Primary outcomes (depressive symptoms and resilience) and secondary outcomes (e.g. anxiety and PTSD, bonding, infant development) will be collected via online questionnaires at four prospective assessments around 20 weeks and 30 weeks gestation and at 6 weeks and 4 months postpartum. Maternal hair cortisol concentrations will be assessed in a subsample of women with a range of depressive symptoms (n = 300). The intervention's feasibility will be assessed through qualitative interviews in a subsample of participants (n = 20). DISCUSSION: This is the first study to assess the effectiveness of an easy to administer intervention strategy to prevent adverse mental health effects through enhancing resilience in pregnant women with antepartum depressive symptomatology. This longitudinal study will provide insights into trajectories of peripartum depressive symptoms in relation to resilience, maternal cortisol, psychological outcomes, and infant developmental milestones. TRIAL REGISTRATION: Netherlands Trial Register (NTR), NL7499 . Registered 5 February 2019.

Experiences of pregnant women with a third trimester routine ultrasound - a qualitative study.

BACKGROUND: Studies showed that pregnant women generally value routine ultrasounds in the first two trimesters because these provide reassurance and a chance to see their unborn baby. This, in turn, might help to decrease maternal anxiety levels and increase the bond with the baby. However, it is unclear whether pregnant women hold the same positive views about a third trimester routine ultrasound, which is increasingly being used in the Netherlands as a screening tool to monitor fetal growth. The aim of this study was to explore pregnant women's experiences with a third trimester routine ultrasound. METHODS: We held semi-structured interviews with fifteen low-risk pregnant women who received a third trimester routine ultrasound in the context of the Dutch IUGR RIsk Selection (IRIS) study. The IRIS study is a nationwide cluster randomized controlled trial carried out among more than 13,000 women to examine the effectiveness of a third trimester routine ultrasound to monitor fetal growth. For the interviews, participants were purposively selected based on parity, age, ethnicity, and educational level. We performed thematic content analysis using MAXQDA. RESULTS: Most pregnant women appreciated a third trimester routine ultrasound because it provided them confirmation that their baby was fine and an extra opportunity to see their baby. At the same time they expressed that they already felt confident about the health of their baby, and did not feel that their bond with their baby had increased after the third trimester ultrasound. Women also reported that they were getting used to routine ultrasounds throughout their pregnancy, and that this increased their need for another one. CONCLUSIONS: Pregnant women seem to appreciate a third trimester routine ultrasound, but it does not seem to reduce anxiety or to improve bonding with their baby. Women's appreciation of a third trimester routine ultrasound might arise from getting used to routine ultrasounds throughout pregnancy. We recommend to examine the psychological impact of third trimester routine ultrasounds in future studies. Results should be taken into consideration when balancing the gains, which are as yet not clear, of introducing a third trimester routine ultrasound against unwanted side effects and costs.

A breast cancer gene signature for indolent disease.

PURPOSE: Early-stage hormone-receptor positive breast cancer is treated with endocrine therapy and the recommended duration of these treatments has increased over time. While endocrine therapy is considered less of a burden to patients compared to chemotherapy, long-term adherence may be low due to potential adverse side effects as well as compliance fatigue. It is of high clinical utility to identify subgroups of breast cancer patients who may have excellent long-term survival without or with limited duration of endocrine therapy to aid in personalizing endocrine treatment. METHODS: We describe a new ultralow risk threshold for the 70-gene signature (MammaPrint) that identifies a group of breast cancer patients with excellent 20 year, long-term survival prognosis. Tumors of these patients are referred to as "indolent breast cancer." We used patient series on which we previously established and assessed the 70-gene signature high-low risk threshold. RESULTS: In an independent validation cohort, we show that patients with indolent breast cancer had 100% breast cancer-specific survival at 15 years of follow-up. CONCLUSIONS: Our data indicate that patients with indolent disease may be candidates for limited treatment with adjuvant endocrine therapy based on their very low risk of distant recurrences or death of breast cancer.

Pregnancy-specific anxiety and its association with background characteristics and health-related behaviors in a low-risk population.

BACKGROUND: Pregnancy-specific anxiety is an important risk factor for adverse pregnancy outcomes. It is therefore needed to gain insight in which women are at risk for elevated levels (> 85th percentile) of pregnancy-specific anxiety. Additionally, given that unhealthy behaviour has been suggested as a possible pathway linking pregnancy-specific anxiety to adverse pregnancy outcomes, it is important to examine whether higher levels of pregnancy-specific anxiety are associated with negative health-related behaviours (smoking, alcohol use and too much weight gain). METHODS: Using a study sample of 4541 low-risk pregnant women who filled in the Pregnancy Related Anxiety Questionnaire-Revised (PRAQ-R), we first examined which socio-demographic, pregnancy-related and psychological background characteristics were significantly associated with a PRAQ-R score above the 85th percentile. Secondly, we examined the association between pregnancy-specific anxiety and self-reported health-related behaviours (smoking, alcohol use and too much weight gain) while controlling for significant background characteristics. For both research questions, backward regression analysis was applied. RESULTS: Results showed that nulliparity (OR=2.33, 95% confidence interval (CI)=1.97-2.77), anxious or depressed mood (OR=3.29, 95% CI=2.74-3.94) and non-Dutch ethnicity, especially Turkish (OR=3.47, 95% CI=2.16-5.59) or Moroccan (OR=2.97, 95% CI=1.84-4.81), were most strongly associated with elevated pregnancy-specific anxiety levels. Women with higher pregnancy-specific anxiety levels were more likely to gain too much weight during pregnancy (odds ratio (OR) linear term=1.49, 95% CI=1.21-1.83), while both very low and high levels of pregnancy-specific anxiety were associated with smoking (OR linear term=0.13, 95% CI=0.04-0.45, OR quadratic term=1.81, 95% CI=1.32-2.47). No association with alcohol use was found. CONCLUSIONS: In conclusion, our results show nulliparity, anxious or depressed mood and non-Dutch ethnicity as three major vulnerability factors for elevated levels of pregnancy-specific anxiety. Furthermore, our results show an association between pregnancy-specific anxiety and negative health-related behaviours, which is worth examining in future studies.

The Association Between Disaster Vulnerability and Post-disaster Psychosocial Service Delivery Across Europe.

This study confirms that the developmental stage of post-disaster psychosocial support planning and delivery systems in Europe is associated with countries' level of disaster vulnerability. Lower vulnerability is accompanied by more evolved planning and delivery systems. Countries in north, west and central regions have more developed planning and delivery systems and lower vulnerability levels than those in the south, southeast and east. The highest proportion of variance in vulnerability is located at the regional level, most of the variance in planning and delivery systems is at the individual level. Possible implications and chances for the optimization of psychosocial services are discussed.

Equivalence of MammaPrint array types in clinical trials and diagnostics.

MammaPrint is an FDA-cleared microarray-based test that uses expression levels of the 70 MammaPrint genes to assess distant recurrence risk in early-stage breast cancer. The prospective RASTER study proved that MammaPrint Low Risk patients can safely forgo chemotherapy, which is further subject of the prospective randomized MINDACT trial. While MammaPrint diagnostic results are obtained from mini-arrays, clinical trials may be performed on whole-genome arrays. Here we demonstrate the equivalence and reproducibility of the MammaPrint test. MammaPrint indices were collected for breast cancer samples: (i) on both customized certified array types (n = 1,897 sample pairs), (ii) with matched fresh and FFPE tissues (n = 552 sample pairs), iii) for control samples replicated over a period of 10 years (n = 11,333), and iv) repeated measurements (n = 280). The array type indicated a near perfect Pearson correlation of 0.99 (95 % CI: 0.989-0.991). Paired fresh and FFPE samples showed an excellent Pearson correlation of 0.93 (95 % CI 0.92-0.94), in spite of the variability introduced by intratumoral tissue heterogeneity. Control samples showed high consistency over 10 year's time (overall reproducibility of 97.4 %). Precision and repeatability are overall 98.2 and 98.3 %, respectively. Results confirm that the combination of the near perfect correlation between array types, excellent equivalence between tissue types, and a very high stability, precision, and repeatability demonstrate that results from clinical trials (such as MINDACT and I-SPY 2) are equivalent to current MammaPrint FFPE and fresh diagnostics, and can be used interchangeably.

Breathing biofeedback as an adjunct to exposure in cognitive behavioral therapy hastens the reduction of PTSD symptoms: a pilot study.

Although trauma-focused cognitive behavioral therapy (TF-CBT) with exposure is an effective treatment for posttraumatic stress disorder (PTSD), not all patients recover. Addition of breathing biofeedback to exposure in TF-CBT is suggested as a promising complementary technique to improve recovery of PTSD symptoms. Patients (n = 8) with chronic PTSD were randomized to regular TF-CBT or TF-CBT with complementary breathing biofeedback to exposure. PTSD symptoms were measured before, during and after TF-CBT with the Impact of Event Scale-Revised. The results show that breathing biofeedback is feasible and can easily be complemented to TF-CBT. Although PTSD symptoms significantly decreased from pre to post treatment in both conditions, there was a clear trend towards a significantly faster (p = .051) symptom reduction in biofeedback compared to regular TF-CBT. The most important limitation was the small sample size. The hastened clinical improvement in the biofeedback condition supports the idea that breathing biofeedback may be an effective complementary component to exposure in PTSD patients. The mechanism of action of breathing biofeedback may relate to competing working memory resources decreasing vividness and emotionality, similar to eye movement desensitization and reprocessing. Future research is needed to examine this.

Executive function in posttraumatic stress disorder (PTSD) and the influence of comorbid depression.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with neurocognitive deficits, such as impaired verbal memory and executive functioning. Less is known about executive function and the role of comorbid depression in PTSD. Recently, studies have shown that verbal memory impairments may be associated with comorbid depressive symptoms, but their role in executive function impairments is still unclear. OBJECTIVE: To examine several domains of executive functioning in PTSD and the potentially mediating role of comorbid depressive symptoms in the relationship between executive function and PTSD. METHOD: Executive functioning was assessed in 28 PTSD patients and 28 matched trauma-exposed controls. The Cambridge Neuropsychological Test Automated Battery (CANTAB) with subtests measuring response inhibition (SST), flexibility/set shifting (IED), planning/working memory (OTS) and spatial working memory (SWM) was administered in PTSD patients and trauma-exposed controls. Regression analyses were used to assess the predictive factor of PTSD symptoms (CAPS) and depressive symptoms (HADS-D) in relation to executive function when taking into account the type of trauma. Pearson's correlations were used to examine the association between PTSD symptom clusters (CAPS) and executive function. The mediating effects of depression and PTSD were assessed using regression coefficients and the Sobel's test for mediation. RESULTS: Our findings indicate that PTSD patients performed significantly worse on executive function than trauma-exposed controls in all domains assessed. PTSD symptoms contributed to executive functioning impairments (SST median correct, IED total errors, OTS latency to correct, SWM total errors and SWM strategy). Adding depressive symptoms to the model attenuated these effects. PTSD symptom clusters 'numbing' and to a lesser extent 'avoidance' were more frequently associated with worse executive function (i.e., IED total errors, OTS latency to correct and SWM total errors) than 'reexperiencing' and 'hyperarousal'. Depressive symptoms mediated the relation between PTSD and executive function on some executive function measures (IED total errors and OTS latency to correct), whereas PTSD did not mediate the relation between depression and executive function. CONCLUSIONS: PTSD patients perform worse on executive function. The impairments seem to be mostly associated with the less specific PTSD symptom cluster of 'numbing'. Depressive symptoms seem to mediate the relationship between PTSD and executive function. These findings may have clinical implications with regard to treatment indication and prognosis.