Pharmakologische Magnetresonanztomographie des Gehirns der Ratte bei hoher magnetischer Feldstärke

Die neuronalen Grundlagen individueller Unterschiede im Angstverhalten sowie die biologischen Ursachen pathologischer Angst sind bisher weitgehend unerforscht. Ein geeignetes Forschungsmodell stellen die Rattenlinien HAB (high anxiety-related behavior) und ihr Gegenstück LAB (low anxiety-related behavior) dar, die durch selektive Züchtung nach dem Kriterium ihres Verhaltens in einem Angsttest für Nager aus einer Normalpopulation hervorgegangen sind. Das Benzodiazepin Diazepam wirkt bei HAB-Ratten wesentlich stärker anxiolytisch als bei LAB-Ratten. Man kann daraus folgern, daß Diazepam differentiell auf Hirnregionen wirken muß, die Angstverhalten steuern. In umgekehrter Logik sollte eine Region, für die gezeigt werden kann, daß sie von Diazepam unterschiedlich angesprochen wird, eine Rolle in der extrem unterschiedlichen Regulation des Angstverhaltens bei den beiden Linien spielen. Zur Identifizierung dieser Kandidatenregionen wurde eine neue Methode zur Kartierung von Hirnaktivierungänderungen, die pharmakologische funktionelle Magnetresonanztomographie (phMRI), erstmals in einem Tomographen der Feldstärke 7 Tesla etabliert. Methodische Besonderheiten der hohen Feldstärke wurden untersucht. Durch den Vergleich der Hirnaktivierungsänderungen nach Diazepam-Gabe zwischen HAB- und LAB-Ratten gelang es, als wichtigste Kandidatenregion für die unterschiedliche Regulation des Angstverhalten den medialen präfrontalen Kortex und das vordere Zingulum (mPFC/ACC) zu identifizieren, eine Region, die von anderen Autoren als Angst-modulierende Region vorgeschlagen wurde. Basierend auf diesen Daten wurde die Hypothese einer Hypoaktivität des mPFC/ACC in hyperängstlichen Individuen entwickelt. Diese Hypothese kann im Tier- sowie Humanmodell getestet werden. Insbesondere ist die Untersuchung der Funktion des mPFC/ACC in Angstpatienten von Interesse, da die Charakterisierung der biologischen Substrate übersteigerten Angstverhaltens grundlegend für das Verständnis der affektiven Erkrankungen und die Entwicklung neuer Therapieansätze ist

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

Animal models and human functional imaging data implicate the dopamine system in mediating enhanced encoding of novel stimuli into human memory. A separate line of investigation suggests an association between a functional polymorphism in the promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to novelty. We demonstrate, in two independent samples, that the -521Cmayor queT DRD4 promoter polymorphism determines the magnitude of human memory enhancement for contextually novel, perceptual oddball stimuli in an allele dose-dependent manner. The genotype-dependent memory enhancement conferred by the C allele is associated with increased neuronal responses during successful encoding of perceptual oddballs in the ventral striatum, an effect which is again allele dose-dependent. Furthermore, with repeated presentations of oddball stimuli, this memory advantage decreases, an effect mirrored by adaptation of activation in the hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus, a dynamic modulation of human memory enhancement for perceptually salient stimuli is associated with activation of a dopaminergic-hippocampal system, which is critically dependent on a functional polymorphism in the DRD4 promoter region

The NMDA agonist D-cycloserine facilitates fear memory consolidation in humans

Animal research suggests that the consolidation of fear and extinction memories depends on N-methyl D-aspartate (NMDA)- type glutamate receptors. Using a fear conditioning and extinction paradigm in healthy normal volunteers, we show that postlearning administration of the NMDA partial agonist D-cycloserine (DCS) facilitates fear memory consolidation, evidenced behaviorally by enhanced skin conductance responses, relative to placebo, for presentations of a conditioned stimulus (CS) at a memory test performed 72 h later. DCS also enhanced CS-evoked neural responses in a posterior hippocampus/collateral sulcus region and in the medial prefrontal cortex at test. Our data suggest a role for NMDA receptors in regulating fear memory consolidation in humans

What helps the helpers? Resilience and risk factors for general and profession-specific mental health problems in psychotherapists during the COVID-19 pandemic

Introduction: Although the COVID-19 pandemic has severely affected wellbeing of at-risk groups, most research on resilience employed convenience samples. We investigated psychosocial resilience and risk factors (RFs) for the wellbeing of psychotherapists and other mental health practitioners, an under-researched population that provides essential support for other at-risk groups and was uniquely burdened by the pandemic. Method: We examined 18 psychosocial factors for their association with resilience, of which four were chosen due to their likely relevance specifically for therapists, in a cross-sectional multi-national sample (N=569) surveyed between June and September 2020. Resilience was operationalized dimensionally and outcome-based as lower stressor reactivity (SR), meaning fewer mental health problems than predicted given a participant’s levels of stressor exposure. General SR (SRG) scores expressed reactivity in terms of general internalizing problems, while profession-specific SR (SRS) scores expressed reactivity in terms of burnout and secondary trauma, typical problems of mental health practitioners. Results: Factors previously identified as RFs in other populations, including perceived social support, optimism and self-compassion, were almost all significant in the study population (SRG: 18/18 RFs, absolute βs=.16-.40; SRS: 15/18 RFs, absolute βs=.19-.39 all Ps <.001). Compassion satisfaction emerged as uniquely relevant for mental health practitioners in regularized regression. Discussion: Our work identifies psychosocial RFs for mental health practitioners’ wellbeing during crisis. Most identified factors are general, in that they are associated with resilience to a wider range of mental health problems, and global, in that they have also been observed in other populations and stressor constellations

What helps the helpers? Resilience and risk factors for general and profession-specific mental health problems in psychotherapists during the COVID-19 pandemic

IntroductionAlthough the COVID-19 pandemic has severely affected wellbeing of at-risk groups, most research on resilience employed convenience samples. We investigated psychosocial resilience and risk factors (RFs) for the wellbeing of psychotherapists and other mental health practitioners, an under-researched population that provides essential support for other at-risk groups and was uniquely burdened by the pandemic.MethodWe examined 18 psychosocial factors for their association with resilience, of which four were chosen due to their likely relevance specifically for therapists, in a cross-sectional multi-national sample (N = 569) surveyed between June and September 2020. Resilience was operationalized dimensionally and outcome-based as lower stressor reactivity (SR), meaning fewer mental health problems than predicted given a participant’s levels of stressor exposure. General SR (SRG) scores expressed reactivity in terms of general internalizing problems, while profession-specific SR (SRS) scores expressed reactivity in terms of burnout and secondary trauma, typical problems of mental health practitioners.ResultsFactors previously identified as RFs in other populations, including perceived social support, optimism and self-compassion, were almost all significant in the study population (SRG: 18/18 RFs, absolute βs = 0.16–0.40; SRS: 15/18 RFs, absolute βs = 0.19–0.39 all Ps &lt; 0.001). Compassion satisfaction emerged as uniquely relevant for mental health practitioners in regularized regression.DiscussionOur work identifies psychosocial RFs for mental health practitioners’ wellbeing during crisis. Most identified factors are general, in that they are associated with resilience to a wider range of mental health problems, and global, in that they have also been observed in other populations and stressor constellations

Population-based validation of a German version of the Brief Resilience Scale

Smith and colleagues developed the Brief Resilience Scale (BRS) to assess the individual ability to recover from stress despite significant adversity. This study aimed to validate the German version of the BRS. We used data from a population-based (sample 1: n = 1.481) and a representative (sample 2: n = 1.128) sample of participants from the German general population (age ≥ 18) to assess reliability and validity. Confirmatory factor analyses (CFA) were conducted to compare one- and two-factorial models from previous studies with a method-factor model which especially accounts for the wording of the items. Reliability was analyzed. Convergent validity was measured by correlating BRS scores with mental health measures, coping, social support, and optimism. Reliability was good (α = .85, ω = .85 for both samples). The method-factor model showed excellent model fit (sample 1: χ2/df = 7.544; RMSEA = .07; CFI = .99; SRMR = .02; sample 2: χ2/df = 1.166; RMSEA = .01; CFI = 1.00; SRMR = .01) which was significantly better than the one-factor model (Δχ2(4) = 172.71, p < .001) or the two-factor model (Δχ2(3) = 31.16, p < .001). The BRS was positively correlated with well-being, social support, optimism, and the coping strategies active coping, positive reframing, acceptance, and humor. It was negatively correlated with somatic symptoms, anxiety and insomnia, social dysfunction, depression, and the coping strategies religion, denial, venting, substance use, and self-blame. To conclude, our results provide evidence for the reliability and validity of the German adaptation of the BRS as well as the unidimensional structure of the scale once method effects are accounted for

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

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