Aktivitätsaufbau ist eine therapeutische Intervention, bei der ein Betroffener lernt, häufiger als bisher aktiv zu handeln. Dabei werden vornehmlich Aktivitäten aufgebaut, die positiv verstärken oder Aversivität von Ereignissen reduzieren bzw. im Einklang mit eigenen Werten stehen. Aktivitätsaufbau ist Element vieler Behandlungsprogramme, einschließlich Digitaler Gesundheitsanwendungen (DiGAs), bildet aber auch den Kern von „Behavioral Activation“ bzw. „Werteorientierter Verhaltensaktivierung“. Aktivitätsaufbau kommt bei unterschiedlichen Störungsbildern zum Einsatz, z. B. bei depressiven Störungen. Es empfiehlt sich, Aktivitätsaufbau in vier Phasen durchzuführen: (1) Instruktion und Messung des Aktivitätsniveaus, (2) Erhöhung des allgemeinen Aktivitätsniveaus, (3) Aufbau spezifischer Aktivitäten, (4) Aufrechterhaltung des Aktivitätsniveaus und spezifischer Aktivitäten.

The medial preoptic nucleus (MPN) plays an essential role in the control of male sexual behavior. In rats, the central part of the MPN (MPNc) contains a sexually dimorphic nucleus exhibiting male-biased morphological sex differences. Although it has been suggested that the MPNc of male rats functions to induce sexual arousal, the mechanisms by which male rats are sexually aroused to successfully achieve copulation are poorly understood. We recently showed that increased neuronal activity in the MPNc of male rats during copulation is higher at their first copulation compared with later copulations, indicating that a plastic change in excitatory synaptic transmission occurs with copulatory experience. In this study, we tested the hypothesis that changes to dendritic spines at structural and molecular levels occur following copulatory experience. First, we examined the effects of at least two copulations on the morphology of dendrites and spines in the MPNc and in the lateral and medial parts of the MPN (MPNlm) of male rats. In the MPNc, the total number of dendrites and their branches, and the surface area of dendrites were not significantly affected by copulation. However, the copulatory experience, specifically experience of ejaculation, significantly reduced the density of mushroom spines but not of filopodia, thin or stubby spines in the MPNc. In the MPNlm, the copulatory experience, specifically experience of ejaculation, significantly increased the surface area of dendrites, although there was no significant effect of copulation on spine density. Next, we measured the mRNA levels of genes encoding actin-binding proteins related to spinogenesis after male rats had copulated for their first and second times. Copulatory stimuli, especially stimuli from ejaculation, significantly reduced the mRNA levels of drebrin A and spinophilin in the MPNc but not in the MPNlm. These results indicate that copulatory experiences, especially experience of ejaculation, reduce spine density in the MPNc of male rats, which may result, in part, from downregulation of genes encoding actin-binding proteins.

Changing working conditions demand adaptation, resulting in higher stress levels in employees. In consequence, decreased productivity, increasing rates of sick leave, and cases of early retirement result in higher direct, indirect, and intangible costs. The aim of the study was to test the usefulness of a novel translational tool, Neuropattern, for early detection, prevention, and personalized treatment of stress-related disorders. The trial was designed as a pilot study with a wait list control group. In this study, 70 employees of the Forestry Department Rhineland-Palatinate, Germany were block-randomized and either underwent Neuropattern immediately, or after a waiting period of three months. After the diagnostic assessment, they received an explanatory disease model and individualized online counseling while their physicians were provided with diagnostic results and treatment recommendations. In order to assess possible beneficial effects of Neuropattern, questionnaires regarding health (SF-12), stress perception (PSS), emotional exhaustion (MBI), work stress (ERI) and work ability (WAI) as well as questions on health behavior were included at several time points. The application of Neuropattern resulted in significantly higher increase in measures of mental health and sporting activity and a significantly stronger decrease in perceived stress, emotional exhaustion and overcommitment, as compared to the control group. No such differences were found with regard to subjects’ physical health, current work ability, reward, effort-reward ratio and practice of relaxation methods. In addition, we unexpectedly found that subjects of the experimental group became significantly more pessimistic regarding their future work ability and showed higher rates of sick leave than control subjects did. These changes remained consistent during 3 and 6 months of follow-up. The present study encouraged the application of Neuropattern to early intervention in non-clinical populations. However, further research is required to determine the best operating conditions.

Psychobiological research has generated a tremendous amount of findings on the psychological, neuroendocrine, molecular and environmental processes that are directly relevant for mental and physical health, but have overwhelmed our capacity to meaningfully absorb, integrate, and utilize this knowledge base. Here, we reflect about suitable strategies to improve the translational success of psychoneuroendocrinological research in the era of precision medicine. Following a strategy advocated by the National Research Council and the tradition of endophenotype based research, we advance here a new approach, termed "conceptual endophenotypes". We define the contextual and formal criteria of conceptual endophenotypes, outline criteria for filtering and selecting information, and describe how conceptual endophenotypes can be validated and implemented at the bedside. As proof-of-concept, we describe some of our findings from research that has adopted this approach in the context of stress-related disorders. We argue that conceptual endophenotypes engineer a bridge between the bench and the bedside. This approach readily lends itself to being continuously developed and implemented. Recent methodological advances, including digital phenotyping, machine learning, grassroots collaboration, and a learning healthcare system, may accelerate the development and implementation of this conceptual endophenotype approach.

Stress is considered to impair health and to be a burden for the individual and the health system. Here, we compared the influence of psychosocial stress and perceived exhaustion as predictors for the development of stress related disorders. Outpatients took part in a clinical trial with Neuropattern, a diagnostic tool to detect stress pathology (Hellhammer, D. H., Hero, T., Gerhards, F., & Hellhammer, J., 2012). The patients answered questions about perceived exhaustion, mental health, psychosocial stress, and demographic variables at their first visit. Further, they answered questions about their health status at five different time points (baseline and 3, 6, 9, and 12 months later). Associations between psychosocial stress, perceived exhaustion, and health status were analyzed at these five time points with mixed models. Furthermore, we explored the potential role of perceived exhaustion as a mediator for the association between psychosocial stress and health status. Both perceived exhaustion and psychosocial stress predicted the development of a poorer health status. Statistical analyses showed the association between psychosocial stress and health status to be mediated by perceived exhaustion. Our findings highlight the importance of perceived exhaustion as a relevant and easy measure to predict the development of impaired health in stress-related disorders.

Impulsivity often develops from disturbed inhibitory control, a function mainly regulated by γ-Aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) and the fronto-striatal system. In this study, we combined MRS GABA measurements and fMRI to investigate neurochemical and neurofunctional correlates of interference inhibition, further emphasizing the direct relationship between those two systems, as well as their relations to impulsivity in patients with BPD. In addition to BOLD activation, task-dependent functional connectivity was assessed by a generalized psychophysiological interactions approach. Full factorial analyses were performed via SPM to examine the main effect (within-group associations) as well as the interaction term (group differences in the association slope). The UPPS scales were used to evaluate impulsivity traits. Compared to healthy controls (HCs), BPD patients exhibited significantly less ACC-caudate functional connectivity during interference inhibition. ACC GABA levels in BPD patients but not in HCs were positively related to the magnitude of activation in several fronto-striatal regions (e.g. ACC, frontal regions, putamen, caudate,) and the strength of ACC-caudate functional connectivity during interference inhibition. The strength of the correlations of GABA with connectivity significantly differs between the two groups. Moreover, among all the UPPS impulsivity subscales, UPPS sensation seeking in the BPD group was related to GABA and was also negatively related to the task-dependent BOLD activation and functional connectivity in the fronto-striatal network. Finally, mediation analyses revealed that the magnitude of activation in the caudate and the strength of ACC-caudate functional connectivity mediated the relationship between ACC GABA levels and UPPS sensation seeking in patients with BPD. Our findings suggest a disconnectivity of the fronto-striatal network in BPD patients during interference inhibition, particularly for patients with higher impulsivity. The ACC GABAergic system seems to play a crucial role in regulating regional BOLD activations and functional connectivity in this network, which are further associated with impulsive sensation seeking in BPD.

We present the case of a patient with symptomatic ventilation-perfusion mismatch due to mixed pulmonary arterial and venous obstruction after partial right lung resection for non-small cell lung cancer. Non-invasive imaging suggested complete occlusion of the right lower lobe pulmonary artery, but we were able to successfully percutaneously recanalize the vessel and improve his symptoms and quality of life.

The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N = 100) conducted in Basel, Switzerland (2007-10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1-3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P = 0.032), EPDS score (P = 0.007) and cortisol AUCgs at T2 (CAR: P = 0.020; DAY: P = 0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment.

BACKGROUND:Poststress symptoms occur as a consequence of stress, most commonly during leisure periods such as weekends and vacations. However, the prevalence and the pathological mechanisms of poststress symptoms are poorly understood.METHODS:Here, we compared the frequency of poststress symptoms in healthy controls (n = 984), outpatients (n = 420), and inpatients (n = 101). In outpatients, demographic factors, psychosocial stress, and perceived exhaustion were tested as predictors of poststress symptoms with multivariate regression analysis. Poststress symptoms and perceived exhaustion were assessed using 2 Neuropattern Questionnaires (the NPQ - Patient Questionnaire and the NPQ - Symptom List), and psychosocial stress was evaluated using the Patient Health Questionnaire (PHQ).RESULTS:Poststress symptoms appeared in 2.9% of healthy controls, 20.0% of outpatients, and 34.7% of inpatients. Predictors were educational level, psychosocial stress, and perceived exhaustion. Poststress symptoms differed primarily between exhausted (75.0%) and nonexhausted patients (25.0%).CONCLUSION:Poststress symptoms are rather common in clinical populations, and they are primarily associated with the degree of perceived exhaustion. Preliminary evidence suggests that poststress symptoms are possibly related to depletion of norepinephrine stores, which may facilitate a stratified preventive and therapeutic treatment of these subjects.

Hintergrund: Verschiedene Studien deuten zunehmend darauf hin, dass Entzündungen ursächlich für psychische Krankheitssymptome bei therapieresistenten depressiven Patienten sein können. Das Risiko für eine entzündungsbedingte Depression scheint durch belastende Lebensereignisse während der frühen Entwicklungsphase des zentralen Nervensystems (ZNS) zu steigen. Da die meisten depressiven Patienten zunächst den Hausarzt aufsuchen, ist eine Früherkennung dieser Zusammenhänge hilfreich. Patienten und Methode: Explorative Analyse an 558 Patienten mit stressbezogenen Erkrankungen. Es wurde untersucht, ob sich depressive von nicht depressiven Patienten hinsichtlich der Häufigkeit entzündlicher Erkrankungen unterscheiden. Des Weiteren wurde die Bedeutsamkeit früher und aktueller Stressbelastung untersucht, und es wurde geprüft, ob depressive Patienten mit rezidivierenden Entzündungen charakteristische Merkmale aufweisen, die für eine Früherkennung nützlich sein können. Ergebnisse: Depressive Patienten zeigten anamnestisch häufiger rezidivierende Entzündungen und Infekte, sie berichteten häufiger über ein «Krankheitsgefühl» sowie über frühkindliche und aktuelle, chronische Stressbelastung. Patienten mit rezidivierenden Entzündungen schilderten ebenfalls häufiger eine frühe und chronische Stressbelastung. Depressive Patienten mit rezidivierenden Entzündungen unterschieden sich von depressiven Patienten ohne Entzündungen durch ein stärkeres Krankheitsgefühl, häufigere stressbezogene Infektionen und schlechtere Wundheilung. Schlussfolgerungen: Unsere Ergebnisse zeigen einen Zusammenhang zwischen einem erhöhten Entzündungsgeschehen, Depressionen und Stressbelastung. Wenn bei Patienten mit therapieresistenter Depression derartige Zusammenhänge erkennbar sind, kann diesem Verdacht nachgegangen und womöglich eine adäquate anti-entzündliche Therapie eingeleitet werden.

Although anuran communication primarily takes place acoustically, chemical cues are also often used for intra- and intersexual communication in frogs. In the present study we analyzed the behavior of the poison frog Ranitomeya variabilis when presented chemical cues of same-sex or opposite-sex conspecifics. Chemical cues were obtained by keeping a single frog on a moist paper towel for about 47 h. Afterwards two paper towels were offered to a test animal, one containing the chemical cues, the other containing rainwater only. We ran trials presenting female cues to males, males cues to males as well as male cues to females. The results of the trials were not significant in terms of intersexual communication. The overall response revealed a clear avoidance strategy which leads us to the assumption that disturbance cues unintentionally occurred during the experiment. The rather small size of the containers used to obtain chemical cues prior to the trials probably lead to confinement stress which consequently caused increased urination containing stress hormones that were detected by the test animals. This is the first proof of disturbance cues and their effects in adult anurans. The results of this study do not allow conclusions about inter- or intrasexual chemical communication of R. variabilis, but they allow implications and revisions for future experiments on this topic.

Pre-, peri-, and postnatal stress have frequently been reported to be associated with negative health outcomes during adult life. However, it is unclear, if these factors independently predict mental health in adulthood. We estimated potential associations between reports of pre-, peri-, and postnatal stress and depression severity in outpatients (N = 473) diagnosed with depression, anxiety or somatoform disorders by their family physician. We retrospectively assessed pre-, peri-, and postnatal stress and measured depression severity as well as recent life stress using questionnaires. First, we estimated if depression severity was predicted by pre-, peri-and/or postnatal stress using multiple regression models. Second, we compared pre- and postnatal stress levels between patient subgroups of different degrees of depression severity, performing multilevel linear modeling. Third, we analyzed if an association between postnatal stress and current depression severity was mediated by recent life stress.We found no associations of pre-, or perinatal stress with depression severity (all p > 0.05). Higher postnatal stress was associated with higher depression severity (p < 0.001). Patients with moderately severe and severe depression reported higher levels of postnatal stress as compared to patients with none to minimal, or mild depression (all p < 0.05). Mediation analysis revealed a significant indirect effect via recent life stress of the association between postnatal stress and depression severity (p < 0.001).In patients diagnosed for depression, anxiety, and/or somatoform disorders, postnatal but neither prenor perinatal stress predicted depression severity in adult life. This association was mediated by recent life stress. (C) 2016 Elsevier Ltd. All rights reserved.

Terrestrial environmental systems are characterised by numerous feedback links between their different compartments. However, scientific research is organized into disciplines that focus on processes within the respective compartments rather than on interdisciplinary links. Major feedback mechanisms between compartments might therefore have been systematically overlooked so far. Without identifying these gaps, initiatives on future comprehensive environmental monitoring schemes and experimental platforms might fail. We performed a comprehensive overview of feedbacks between compartments currently represented in environmental sciences and explores to what degree missing links have already been acknowledged in the literature. We focused on process models as they can be regarded as repositories of scientific knowledge that compile findings of numerous single studies. In total, 118 simulation models from 23 model types were analysed. Missing processes linking different environmental compartments were identified based on a meta-review of 346 published reviews, model intercomparison studies, and model descriptions. Eight disciplines of environmental sciences were considered and 396 linking processes were identified and ascribed to the physical, chemical or biological domain. There were significant differences between model types and scientific disciplines regarding implemented interdisciplinary links. The most wide-spread interdisciplinary links were between physical processes in meteorology, hydrology and soil science that drive or set the boundary conditions for other processes (e.g., ecological processes). In contrast, most chemical and biological processes were restricted to links within the same compartment. Integration of multiple environmental compartments and interdisciplinary knowledge was scarce in most model types. There was a strong bias of suggested future research foci and model extensions towards reinforcing existing interdisciplinary knowledge rather than to open up new interdisciplinary pathways. No clear pattern across disciplines exists with respect to suggested future research efforts. There is no evidence that environmental research would clearly converge towards more integrated approaches or towards an overarching environmental systems theory.

Erschöpfung kennzeichnet zahlreiche psychische Störungen. Wir haben geprüft, ob die subjektive Erschöpfungsqualität ein verlässlicher Indikator für stressbezogene Gesundheitsstörungen und den daraus resultierenden direkten, indirekten und intangiblen Gesundheitskosten ist. Zur Anwendung kam eine Erschöpfungsskala (Neuropattern-Questionnaire, NPQ-S), deren Cut-off-Werte und Reliabilität anhand einer bevölkerungsrepräsentativen Stichprobe (N = 998) ermittelt wurden. Die Validität wurde bei ambulanten Patienten (N = 455) über Angaben zu psychischen Erkrankungen, gesundheitsbezogenen Kosten und strukturierten Anamnesen sowie einer berufshomogene Stichprobe mit stressbezogenen Beschwerden (N = 69) über Angaben zu Burnout und Gratifikationskrisen untersucht. Die Reliabilität und Validität der Erschöpfungsqualität konnten als gut bis sehr gut eingestuft werden. Die Ergebnisse zeigten, dass ein erhöhtes Ausmaß an Erschöpfung mit erhöhter Stressbelastung, einer erhöhten Chance für verschiedene psychische Erkrankungen sowie erhöhten Kosten (reduziertes Wohlbefinden, häufigere Therapeuten- und Arztbesuche, erhöhter Medikamentenkonsum, mehr Arbeitsunfähigkeitstage) einhergeht. Die Erschöpfungsqualität zeigt sich als störungsübergreifender Indikator und kann als ökonomisches Indikations- und Evaluationsmaß für gesundheitsförderliche Maßnahmen dienen.

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30-45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. The present report summarizes the results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research.

Ambient air pollution is associated with systemic increases in oxidative stress, to which sperm are particularly sensitive. Although decrements in semen quality represent a key mechanism for impaired fecundability, prior research has not established a clear association between air pollution and semen quality. To address this, we evaluated the association between ambient air pollution and semen quality among men with moderate air pollution exposure.Of 501 couples in the LIFE study, 467 male partners provided one or more semen samples. Average residential exposure to criteria air pollutants and fine particle constituents in the 72 days before ejaculation was estimated using modified Community Multiscale Air Quality models. Generalized estimating equation models estimated the association between air pollutants and semen quality parameters (volume, count, percent hypo-osmotic swollen, motility, sperm head, morphology and sperm chromatin parameters). Models adjusted for age, body mass index, smoking and season.Most associations between air pollutants and semen parameters were small. However, associations were observed for an interquartile increase in fine particulates ≤2.5 µm and decreased sperm head size, including −0.22 (95% CI −0.34, −0.11) µm2 for area, −0.06 (95% CI −0.09, −0.03) µm for length and −0.09 (95% CI −0.19, −0.06) µm for perimeter. Fine particulates were also associated with 1.03 (95% CI 0.40, 1.66) greater percent sperm head with acrosome.Air pollution exposure was not associated with semen quality, except for sperm head parameters. Moderate levels of ambient air pollution may not be a major contributor to semen quality.