The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

Culturally sensitive stepped care for adolescent refugees: efficacy and cost-utility of a multicentric randomized controlled trial.

Adolescent refugees and asylum seekers (ARAS) are highly vulnerable to mental health problems. Stepped care models (SCM) and culturally sensitive therapies offer promising treatment approaches to effectively provide necessary medical and psychological support. To our knowledge, we were the first to investigate whether a culturally sensitive SCM will reduce symptoms of depression and PTSD in ARAS more effectively and efficiently than treatment as usual (TAU). We conducted a multicentric, randomized, controlled and rater-blinded trial across Germany with ARAS between the ages of 14 to 21 years. Participants (N = 158) were stratified by their level of depressive symptom severity and then equally randomized to either SCM or TAU. Depending on their severity level, SCM participants were allocated to tailored interventions. Symptom changes were assessed for depression (PHQ) and PTSD (CATS) at four time points, with the primary end point at post-intervention after 12 weeks. Based on an intention-to-treat sample, we used a linear mixed model approach for the main statistical analyses. Further evaluations included cost-utility analyses, sensitivity analyses, follow-up-analyses, response and remission rates and subgroup analysis. We found a significant reduction of PHQ (d = 0.52) and CATS (d = 0.27) scores in both groups. However, there was no significant difference between SCM and TAU. Cost-utility analyses indicated that SCM generated greater cost-utility when measured as quality-adjusted life years compared to TAU. Subgroup analysis revealed different effects for the SCM interventions depending on the outcome measure. Although culturally sensitive, SCMs did not prove to be more effective in symptom change and represent a more cost-effective treatment alternative for mentally burdened ARAS. Our research contributes to the optimization of clinical productivity and the improvement of therapeutic care for ARAS. Disorder-specific interventions should be further investigated.

Environmental stress, minority status, and local poverty: risk factors for mental health in Berlin's inner city.

This study examines whether climate change-associated environmental stressors, including air and noise pollution, local heat levels, as well as a lack of surrounding greenspace, mediate the effects of local poverty on mental health, using the 28-item General Health Questionnaire. We recruited 478 adults who were representative of eleven of Berlin's inner-city neighborhoods. The relationship of individual-level variables, neighborhood-level sociodemographic and environmental data from the Berlin Senate (Department for Urban Development, Building and Housing) to mental health was assessed in a multilevel model using SPSS. We found that neither local exposure to environmental stressors, nor available greenspace as a protective factor, mediated the effects of local poverty on variance in mental health (all p values > 0.2). However, surrounding greenspace (r = -0.24, p < 0.001), nitrogen dioxide levels (r = 0.10, p < 0.05), noise pollution (rho = 0.15, p < 0.01), and particle pollution (r = 0.12, p < 0.001) were associated with local poverty, which, more strongly than individual factors, accounted for variance in mental health (ß = 0.47, p < 0.001). Our analysis indicates that the effects of local poverty on mental health are not mediated by environmental factors. Instead, local poverty was associated with both an increased mental health burden and the exposure to climate-related environmental stressors.

Mapping Research Domain Criteria using a transdiagnostic mini-RDoC assessment in mental disorders: a confirmatory factor analysis.

This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix.

Lithium Therapy in Old Age: Recommendations from a Delphi Survey.

INTRODUCTION: While lithium (Li) has been well established for the treatment of bipolar disorder, geriatric patients require special attention when it comes to issues of drug safety. Declining renal function, amongst other medical conditions, and polypharmacy may pose increased risks. Only a few previous studies have addressed the management of Li in geriatric patients. METHODS: Twenty-four German medical experts on geriatric medicine and Li treatment participated in a Delphi survey, consisting of two rounds of questionnaires and a final formulation of treatment recommendations. Three major issues of Li therapy were outlined: initiation of treatment, monitoring of ongoing therapy, and withdrawal due to medical reasons. Final recommendations were consented to at a threshold of at least 80% expert agreement. RESULTS: Final consensus was achieved on 21 clinical recommendations. The approved recommendations covered aspects of necessary laboratory checks, concomitant medication, and target Li serum concentration in geriatric patients. Concerning the termination of Li therapy, an agreement was reached on the appropriate time span for tapering and on potential alternatives to Li. No consensus was achieved on whether concomitant dementia or frailty should be considered contraindications for Li treatment and the appropriate threshold of the estimated glomerular function rate for withdrawing Li. CONCLUSION: According to the view of German experts, Li may be used in geriatric patients, but it should be monitored carefully. However, the lack of consent in several specific treatment situations underlines the need for research on specific issues of Li therapy.

Susceptibility to interference between Pavlovian and instrumental control predisposes risky alcohol use developmental trajectory from ages 18 to 24.

Pavlovian cues can influence ongoing instrumental behaviour via Pavlovian-to-instrumental transfer (PIT) processes. While appetitive Pavlovian cues tend to promote instrumental approach, they are detrimental when avoidance behaviour is required, and vice versa for aversive cues. We recently reported that susceptibility to interference between Pavlovian and instrumental control assessed via a PIT task was associated with risky alcohol use at age 18. We now investigated whether such susceptibility also predicts drinking trajectories until age 24, based on AUDIT (Alcohol Use Disorders Identification Test) consumption and binge drinking (gramme alcohol/drinking occasion) scores. The interference PIT effect, assessed at ages 18 and 21 during fMRI, was characterized by increased error rates (ER) and enhanced neural responses in the ventral striatum (VS), the lateral and dorsomedial prefrontal cortices (dmPFC) during conflict, that is, when an instrumental approach was required in the presence of an aversive Pavlovian cue or vice versa. We found that a stronger VS response during conflict at age 18 was associated with a higher starting point of both drinking trajectories but predicted a decrease in binge drinking. At age 21, high ER and enhanced neural responses in the dmPFC were associated with increasing AUDIT-C scores over the next 3 years until age 24. Overall, susceptibility to interference between Pavlovian and instrumental control might be viewed as a predisposing mechanism towards hazardous alcohol use during young adulthood, and the identified high-risk group may profit from targeted interventions.

The relationship between pre-surgery self-rated health and changes in functional and mental health in older adults: insights from a prospective observational study.

BACKGROUND: Elective surgeries are among the most common health stressors in later life and put a significant risk at functional and mental health, making them an important target of research into healthy aging and physical resilience. Large-scale longitudinal research mostly conducted in non-clinical samples provided support of the predictive value of self-rated health (SRH) for both functional and mental health. Thus, SRH may have the potential to predict favorable adaptation processes after significant health stressors, that is, physical resilience. So far, a study examining the interplay between SRH, functional and mental health and their relative importance for health changes in the context of health stressors was missing. The present study aimed at addressing this gap. METHODS: We used prospective data of 1,580 inpatients (794 complete cases) aged 70 years or older of the PAWEL study, collected between October 2017 and May 2019 in Germany. Our analyses were based on SRH, functional health (Barthel Index) and self-reported mental health problems (PHQ-4) before and 12 months after major elective surgery. To examine changes and interrelationships in these health indicators, bivariate latent change score (BLCS) models were applied. RESULTS: Our analyses provided evidence for improvements of SRH, functional and mental health from pre-to-post surgery. BLCS models based on complete cases and the total sample pointed to a complex interplay of SRH, functional health and mental health with bidirectional coupling effects. Better pre-surgery SRH was associated with improvements in functional and mental health, and better pre-surgery functional health and mental health were associated with improvements in SRH from pre-to-post surgery. Effects of pre-surgery SRH on changes in functional health were smaller than those of functional health on changes in SRH. CONCLUSIONS: Meaningful changes of SRH, functional and mental health and their interplay could be depicted for the first time in a clinical setting. Our findings provide preliminary support for SRH as a physical resilience factor being associated with improvements in other health indicators after health stressors. Longitudinal studies with more timepoints are needed to fully understand the predictive value of SRH for multidimensional health. TRIAL REGISTRATION: PAWEL study, German Clinical Trials Register, number DRKS00013311. Registered 10 November 2017 - Retrospectively registered, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013311 .

Frailty index and its association with the onset of postoperative delirium in older adults undergoing elective surgery.

BACKGROUND: The association of frailty based on the accumulation of deficits with postoperative delirium (POD) has been poorly examined. We aimed to analyze this association in older patients undergoing elective surgery. METHODS: Preoperative data was used to build a 30-item frailty index (FI) for participants of the PAWEL-study. Delirium was defined by a combination of I-CAM and chart review. Using logistic regressions models we analysed the association between frailty and POD adjusting for age, sex, smoking, alcohol consumption, education and type of surgery. RESULTS: Among 701 participants (mean age 77.1, 52.4% male) median FI was 0.27 (Q1 0.20| Q3 0.34), with 528 (75.3%) frail participants (FI ≥ 0.2). Higher median FI were seen in orthopedic than cardiac surgery patients (0.28 versus 0.23), and in women (0.28 versus 0.25 in men). Frail participants showed a higher POD incidence proportion (25.4% versus 17.9% in non-frail). An increased odds for POD was observed in frail versus non-frail participants (OR 2.14 [95% CI 1.33, 3.44], c-statistic 0.71). A 0.1 increment of FI was associated with OR 1.57 [95% CI 1.30, 1.90] (c-statistic 0.72) for POD. No interaction with sex or type of surgery was detected. Adding timed-up-and-go-test and handgrip strength to the FI did not improve discrimination. CONCLUSION: Our data showed a significant association between frailty defined through a 30-item FI and POD among older adults undergoing elective surgery. Adding functional measures to the FI did not improve discrimination. Hence, our preoperative 30-item FI can help to identify patients with increased odds for POD. TRIAL REGISTRATION: PAWEL and PAWEL-R (sub-) study were registered on the German Clinical Trials Register (number DRKS00013311 and DRKS00012797).

Effect of acute and long-term exercise on leptin levels in depressed outpatients.

BACKGROUND: Depression is a leading cause of disability worldwide and a significant contributor to the global burden of disease. Altered leptin levels are known to be associated with depressive symptoms, however discrepancies in the results of increased or decreased levels exist. Due to various limitations associated with commonly used antidepressant drugs, alternatives such as exercise therapy are gaining more importance. Therefore, the current study investigates whether depressed patients have higher leptin levels compared to healthy controls and if exercise is efficient to reduce these levels. METHODS: Leptin levels of 105 participants with major depressive disorder (MDD; 45.7% female, age mean ± SEM: 39.1 ± 1.0) and 34 healthy controls (HC; 61.8% female, age mean ± SEM: 36.0 ± 2.0) were measured before and after a bicycle ergometer test. Additionally, the MDD group was separated into three groups: two endurance exercise intervention groups (EX) differing in their intensities, and a waiting list control group (WL). Leptin levels were measured pre and post a 12-week exercise intervention or the waiting period. RESULTS: Baseline data showed no significant differences in leptin levels between the MDD and HC groups. As expected, correlation analyses displayed significant relations between leptin levels and body weight (HC: r = 0.474, p = 0.005; MDD: r = 0.198, p = 0.043) and even more with body fat content (HC: r = 0.755, p < 0.001; MDD: r = 0.675, p < 0.001). The acute effect of the bicycle ergometer test and the 12-week training intervention showed no significant changes in circulating leptin levels. CONCLUSION: Leptin levels were not altered in patients with major depression compared to healthy controls and exercise, both the acute response and after 12 weeks of endurance training, had no effect on the change in leptin levels. TRIAL REGISTRATION: The study was registered at the German register for clinical studies (DRKS) and the International Clinical Trials Registry Platform of the World Health Organization https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00008869 on 28/07/2015.

Predictors and prevalence of hazardous alcohol use in middle-late to late adulthood in Europe.

Objectives: Even low to moderate levels of alcohol consumption can have detrimental health consequences, especially in older adults (OA). Although many studies report an increase in the proportion of drinkers among OA, there are regional variations. Therefore, we examined alcohol consumption and the prevalence of hazardous alcohol use (HAU) among men and women aged 50+ years in four European regions and investigated predictors of HAU.Methods: We analyzed data of N = 35,042 participants of the European SHARE study. We investigated differences in alcohol consumption (units last week) according to gender, age and EU-region using ANOVAs. Furthermore, logistic regression models were used to examine the effect of income, education, marital status, history of a low-quality parent-child relationship and smoking on HAU, also stratified for gender and EU-region. HAU was operationalized as binge drinking or risky drinking (<12.5 units of 10 ml alcohol/week).Results: Overall, past week alcohol consumption was 5.0 units (±7.8), prevalence of HAU was 25.4% within our sample of European adults aged 50+ years. Male gender, younger age and living in Western Europe were linked to both higher alcohol consumption and higher risks of HAU. Income, education, smoking, a low-quality parent-child relationship, living in Northern and especially Eastern Europe were positively associated with HAU. Stratified analyses revealed differences by region and gender.Conclusions: HAU was highly prevalent within this European sample of OA. Alcohol consumption and determinants of HAU differed between EU-regions, hinting to a necessity of risk-stratified population-level strategies to prevent HAU and subsequent alcohol use disorders.

[Development of an Index of Social Structures to Determine the Sociostructural Need for Physicians in Outpatient Care in Brandenburg]. / Entwicklung eines Sozialstrukturindex zur Ermittlung des soziostrukturellen Versorgungsbedarfs in der ambulanten medizinischen Versorgung in Brandenburg.

INTRODUCTION: Despite the growing numbers of physicians in outpatient care, continuing discussion about the planning of physician requirements suggests remaining problems in this field, which could be due to focussing on the ratio of physician to population rather than on morbidity-based evaluations. Against this background, this paper tries to depict the latent need in outpatient care, illustrates supply and demand and further tests the hypothesis that there is a relative inequality in distribution due to physicians preferring to locate in socially privileged areas in the German state of Brandenburg. METHODS: We aggregated all data available on a small scale with potential impact on demand and examined it via principal component analysis. The generated factor was mapped together with the locations of general practitioners and specialists in general care. Using linear regressions, the number of practitioners was compared to the local index value to determine regional inequalities. RESULTS: The PCA suggested a one factor solution; that factor was designated Social Structure Index due to its values. The mapping showed a tendency of higher index values towards the central areas of Brandenburg surrounding Berlin. Regressions of the number of practitioners against the index values revealed no significant differences between communities with high and low index values. CONCLUSION: The extension of factors concluding the evaluation of physician demand in outpatient care confirms the problems of physician supply in rural areas, where sparse populations meet social disadvantages and poor accessibility. An underlying inequality in distribution in terms of physicians preferring socially privileged areas could not be detected.

[Access to cardiological care infrastructure in the federal state of Brandenburg considering the local care needs]. / Erreichbarkeit der kardiologischen Versorgungsinfrastruktur im Bundesland Brandenburg in Abhängigkeit des lokalen Versorgungsbedarfs.

AIM OF THE STUDY: In a nationwide comparison, the state of Brandenburg has one of the highest morbidity and mortality rates of ischemic heart disease. Access to medical care infrastructure is considered to be one possible explanation for regional health inequalities. Accordingly, the study aims to calculate the distances to different types of cardiology care at the community level and to consider these in the context of local care needs. METHODOLOGY: Preventive sports facilities, general practitioners, outpatient specialist care, hospitals with cardiac catheterization laboratory and outpatient rehabilitation were chosen and mapped as essential facilities for cardiological care. Thereafter, the distances across the road network from the center of each Brandenburg community to the nearest location of each care facility was calculated and divided into quintiles. Medians and interquartile ranges of the German Index of Socioeconomic Deprivation and the proportion of the population over 65 were used as measures of the need for care. They were then related to the distance quintiles per type of care facility. RESULTS: For 60% of Brandenburg's municipalities, general practitioners were found to be within 2.5 km, preventive sports facilities within 19.6 km, cardiology practices within 18.3 km, hospitals with cardiac catheterization laboratories within 22.7 km, and outpatient rehabilitation facilities within 14.7 km. The median of the German Index of Socioeconomic Deprivation rose with increasing distance for all types of care facilities. The median of the proportion of over 65-year-olds showed no significant variation between distance quintiles. CONCLUSIONS: The results show that a high proportion of the population lives far away from cardiology care services, while a high proportion seems to be able to reach a general practitioner. In Brandenburg, a regional and locally oriented cross-sectoral care seems to be necessary.

Measuring self-regulation in everyday life: Reliability and validity of smartphone-based experiments in alcohol use disorder.

Self-regulation, the ability to guide behavior according to one's goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test-retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures' construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks.

Recreational exercise is associated with lower prevalence of depression and anxiety and better quality of life in German people living with HIV.

Sedentarism is a risk factor for depression and anxiety. People living with the human immunodeficiency virus (PLWH) have a higher prevalence of anxiety and depression compared to HIV-negative individuals. This cross-sectional study (n = 450, median age 44 (19-75), 7.3% females) evaluates the prevalence rates and prevalence ratio (PR) of anxiety and/or depression in PLWH associated with recreational exercise. A decreased likelihood of having anxiety (PR=0.57; 0.36-0.91; p = 0.01), depression (PR=0.41; 0.36-0.94; p=0.01), and comorbid anxiety and depression (PR = 0,43; 0.24-0.75; p=0.002) was found in exercising compared to non-exercising PLWH. Recreational exercise is associated with a lower risk for anxiety and/or depression. Further prospective studies are needed to provide insights on the direction of this association.

Mobile Data Collection of Cognitive-Behavioral Tasks in Substance Use Disorders: Where Are We Now?

INTRODUCTION: Over the last decades, our understanding of the cognitive, motivational, and neural processes involved in addictive behavior has increased enormously. A plethora of laboratory-based and cross-sectional studies has linked cognitive-behavioral measures to between-subject differences in drinking behavior. However, such laboratory-based studies inevitably suffer from small sample sizes and the inability to link temporal fluctuations in task measures to fluctuations in real-life substance use. To overcome these problems, several existing behavioral tasks have been transferred to smartphones to allow studying cognition in the field. METHOD: In this narrative review, we first summarize studies that used existing behavioral tasks in the laboratory and self-reports of substance use with ecological momentary assessment (EMA) in the field. Next, we review studies on psychometric properties of smartphone-based behavioral tasks. Finally, we review studies that used both smartphone-based tasks and self-reports with EMA in the field. RESULTS: Overall, studies were scarce and heterogenous both in tasks and in study outcomes. Nevertheless, existing findings are promising and point toward several methodological recommendations: concerning psychometrics, studies show that - although more systematic studies are necessary - task validity and reliability can be improved, for example, by analyzing several measurement sessions at once rather than analyzing sessions separately. Studies that use tasks in the field, moreover, show that power can be improved by choosing sampling schemes that combine time-based with event-based sampling, rather than relying on time-based sampling alone. Increasing sampling frequency can further increase power. However, as this also increases the burden to participants, more research is necessary to determine the ideal sampling frequency for each task. CONCLUSION: Although more research is necessary to systematically study both the psychometrics of smartphone-based tasks and the frequency at which task measures fluctuate, existing studies are promising and reveal important methodological recommendations useful for researchers interested in implementing behavioral tasks in EMA studies.

Pavlovian-to-Instrumental Transfer across Mental Disorders: A Review.

A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects. Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity. In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects. We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability. Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting. To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions.

A theory of change of an innovation for therapeutic care and meaningful living in a German nursing home.

BACKGROUND: Demographic changes are leading to growing care needs of older people and creating a challenge for healthcare systems worldwide. Nursing homes (NHs) need to provide care for growing numbers of residents while ensuring a high-quality care. We aimed to examine an innovative NH in Germany and apply a theory of change (ToC) approach to develop a best practice model (BPM) for therapeutic care in NHs. METHODS: A multimethod qualitative study conducted from February to July 2021 in Germany involved interviews with 14 staff members of an innovative NH and 10 directors and care managers of other NHs. The interview guidelines included questions on nursing practices, infrastructure, resources, interprofessional collaboration, and working culture. Additional material on the participating NH (website, promotion videos, newsletters, care documentation) were collected. Contextual literature on NH culture and therapeutic care in Germany, ToC methodology, and NH culture change were reviewed. Following a question-focused analysis of all material, we generated a ToC model towards a BPM of therapeutic care and meaningful living in NHs. Results were verified in interdisciplinary team meetings, with study participants and other stakeholders to establish consensus. RESULTS: The participating NH's care concept aims to improve residents' functional abilities and wellbeing as well as staff members' job satisfaction. Central components of their approach include therapeutic elements such as music and movement in all nursing activities, multidisciplinary collaboration, a broad therapy and social activity offer, the continuation of therapy in everyday activities, a focus on individual life history, values, needs, and skills, social integration into the regional community, and the creation of a meaningful living environment for residents and staff. CONCLUSION: The BPM we developed shows how a meaningful living environment can be created through therapeutic care and integrative activities. The ToC sheds light onto the contextual factors and cultural values which should be considered in the development of NH interventions. Research on not only biomedical aspects, but also psychosocial dynamics and narrative co-constructions in nursing practice should inform NH innovations. The ToC also highlights the importance of developing adequate political frameworks and infrastructures for implementing such innovative practices on a larger scale.

Psychosocial burden in nurses working in nursing homes during the Covid-19 pandemic: a cross-sectional study with quantitative and qualitative data.

BACKGROUND: The Covid-19 pandemic led to increased work-related strain and psychosocial burden in nurses worldwide, resulting in high prevalences of mental health problems. Nurses in long-term care facilities seem to be especially affected by the pandemic. Nevertheless, there are few findings indicating possible positive changes for health care workers. Therefore, we investigated which psychosocial burdens and potential positive aspects nurses working in long-term care facilities experience during the Covid-19 pandemic. METHODS: We conducted a mixed-methods study among nurses and nursing assistants working in nursing homes in Germany. The survey contained the third German version of the Copenhagen Psychosocial Questionnaire (COPSOQ III). Using Welch's t-tests, we compared the COPSOQ results of our sample against a pre-pandemic reference group of geriatric nurses from Germany. Additionally, we conducted semi-structured interviews with geriatric nurses with a special focus on psychosocial stress, to reach a deeper understanding of their experiences on work-related changes and burdens during the pandemic. Data were analysed using thematic coding (Braun and Clarke). RESULTS: Our survey sample (n = 177) differed significantly from the pre-pandemic reference group in 14 out of 31 COPSOQ scales. Almost all of these differences indicated negative changes. Our sample scored significantly worse regarding the scales 'quantitative demands', 'hiding emotions', 'work-privacy conflicts', 'role conflicts', 'quality of leadership', 'support at work', 'recognition', 'physical demands', 'intention to leave profession', 'burnout', 'presenteeism' and 'inability to relax'. The interviews (n = 15) revealed six main themes related to nurses' psychosocial stress: 'overall working conditions', 'concern for residents', 'management of relatives', 'inability to provide terminal care', 'tensions between being infected and infecting others' and 'technicisation of care'. 'Enhanced community cohesion' (interviews), 'meaning of work' and 'quantity of social relations' (COPSOQ III) were identified as positive effects of the pandemic. CONCLUSIONS: Results clearly illustrate an aggravation of geriatric nurses' situation and psychosocial burden and only few positive changes due to the Covid-19 pandemic. Pre-existing hardships seem to have further deteriorated and new stressors added to nurses' strain. The perceived erosion of care, due to an overemphasis of the technical in relation to the social and emotional dimensions of care, seems to be especially burdensome to geriatric nurses.

Block of Voltage-Gated Sodium Channels by Aripiprazole in a State-Dependent Manner.

Aripiprazole is an atypical antipsychotic drug, which is prescribed for many psychiatric diseases such as schizophrenia and mania in bipolar disorder. It primarily acts as an agonist of dopaminergic and other G-protein coupled receptors. So far, an interaction with ligand- or voltage-gated ion channels has been classified as weak. Meanwhile, we identified aripiprazole in a preliminary test as a potent blocker of voltage-gated sodium channels. Here, we present a detailed analysis about the interaction of aripiprazole with the dominant voltage-gated sodium channel of heart muscle (hNav1.5). Electrophysiological experiments were performed by means of the patch clamp technique at human heart muscle sodium channels (hNav1.5), heterologously expressed in human TsA cells. Aripiprazole inhibits the hNav1.5 channel in a state- but not use-dependent manner. The affinity for the resting state is weak with an extrapolated Kr of about 55 µM. By contrast, the interaction with the inactivated state is strong. The affinities for the fast and slow inactivated state are in the low micromolar range (0.5-1 µM). Kinetic studies indicate that block development for the inactivated state must be described with a fast (ms) and a slow (s) time constant. Even though the time constants differ by a factor of about 50, the resulting affinity constants were nearly identical (in the range of 0.5 µM). Besides this, aripirazole also interacts with the open state of the channel. Using an inactivation deficit mutant, an affinity of about 1 µM was estimated. In summary, aripiprazole inhibits voltage-gated sodium channels at low micromolar concentrations. This property might add to its possible anticancer and neuroprotective properties.

Dopamine D2/3 receptor availability in alcohol use disorder and individuals at high risk: Towards a dimensional approach.

Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying 18 F-fallypride positron emission tomography (18 F-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future.