The interplay of personality pathology and treatment outcome in psychosomatic psychotherapy: A longitudinal analysis using latent change score modelling.

INTRODUCTION: While ample data demonstrate the effectiveness of inpatient psychosomatic treatment, clinical observation and empirical evidence demonstrate that not all patients benefit equally from established therapeutic methods. Especially patients with a comorbid personality disorder often show reduced therapeutic success compared to other patient groups. Due to the heterogeneous and categorical personality assessment, previous studies indicated no uniform direction of this influence. This complicates the derivation of therapeutic recommendations for mental disorders with comorbid personality pathology. METHODS: Analyzing n = 2094 patients from German university hospitals enrolled in the prospective "MEPP" study, we tested the dynamic interaction between dimensionally assessed personality functioning and psychopathology of anxiety and depression. RESULTS: Longitudinal structural equation modelling replicated the finding that the severity of symptoms at admission predicts symptom improvement within the same symptom domain. In addition, we here report a significant coupling parameter between the baseline level of personality function and the change in general psychopathology - and vice versa. DISCUSSION AND CONCLUSION: These results imply that personality pathology at admission hinders the therapeutic improvement in anxiety and depression, and that improvement of personality pathology is hindered by general psychopathology. Furthermore, the covariance between both domains supports the assumption that personality functioning and general psychopathology cannot be clearly distinguished and adversely influence each other. A dimensional assessment of the personality pathology is therefore recommendable for psychotherapy research and targeted therapeutic treatment.

Unveiling social relationships: exploring the importance of relationships as a moderator of the link between effort-reward imbalance and leader-member exchange among healthcare professionals.

OBJECTIVE: Healthcare professionals are at increased risk of experiencing occupational stress and its detrimental stress-sequalae. Relevant theories that contribute to the subjective experience of occupational stress have been identified, such as the model of effort-reward imbalance (ERI) and the concept of leader-member exchange (LMX). The aim of this study was to examine how the perceived importance of social relationships at work moderates the relationship between LMX and imbalance ERI. METHODS: A survey was conducted among N = 1,137 healthcare professionals from diverse occupational categories in a tertiary hospital in Germany. ERI was gauged using the German version of the Effort-Reward Imbalance Questionnaire (ERI-S 10). The quality of leader-employee dyadic relationships was assessed using the German version of the Leader-Member Exchange (LMX-7). The importance of social relationships was assessed on the basis of a previously validated polarity profile. RESULTS: More than 75% of healthcare professionals reported high levels of ERI, with those involved in direct patient care particularly affected. On average, leaders rated relationship quality higher than their respective followers. Subjectively higher LMX was associated with lower ERI. This association was moderated by the perceived importance of social relationships at work. Higher subjective ratings of their importance led to a stronger association. CONCLUSION: The study highlights the particular challenges faced in the healthcare sector. The results emphasize that the perceived importance of social relationships at work can play a key role in healthcare professionals' job stress and underline the need for stress prevention programs that engage both leaders and followers.

Leaders' mental health and leader-member exchange: Exploring relations on different levels of analysis.

INTRODUCTION: Research on leader-member exchange (LMX) has shown that the relation between leaders and followers may be considered from different angles. Leaders may form individual relationships with followers (LMX quality), may agree with their followers on these relationships (LMX agreement), and may form different relationships within their work group (LMX variability). We posit that leaders' mental health may function as an antecedent for these different forms of LMX. We use conservation-of-resources theory as a theoretical model to describe how leaders' mental health may interact with relationship quality with followers on different levels. METHODS: We operationalized leaders' mental health using depressive symptoms, anxiety, and stress reactivity. Our sample consisted of 322 followers of 75 leaders. Followers rated the LMX quality with their respective leader. Leaders rated depressive symptoms, anxiety, levels of stress reactivity, and LMX quality with their followers. RESULTS: Results of multilevel modeling showed that stress reactivity was negatively related to LMX quality and anxiety was positively linked to LMX agreement. Depressive symptoms were not related to aspects of LMX. CONCLUSION: By using multisource data on different analysis levels, we are able to include different perspectives on antecedents of LMX relationship quality. Implications for LMX at different levels of analysis as well as future research are discussed.

[Rationale, models, and impact of workplace-based psychotherapeutic services]. / Rationale, Modelle und Wirkung arbeitsplatznaher psychotherapeutischer Angebote.

Mental illnesses and behavioral disorders are very common among the working population, affecting up to a third of employees each year, and are associated with great suffering, the risk of chronicity, and the loss of employment. Economically, mental illnesses cause high costs. In order to mitigate these consequences and increase the chances of recovery, rapid diagnosis, early and appropriate treatment where necessary, and-over and above the usual psychotherapy approach-attention to the work-related causes are of crucial importance.Psychotherapeutic Consultation at the Workplace (PT-A) attempts to meet these requirements. It offers psychotherapeutic help at short notice and close to the workplace for employees suffering from mental stress; provides (depending on the problem) counseling, diagnostics, prevention, and short-term or bridging therapy; and supports reintegration after a longer period of mental illness. It is helpful to cooperate closely with the company medical service, which consults the PT­A, refers employees to it, provides information on the company situation, and can support reintegration if necessary. Funding is often provided by the company but can also be provided by health insurance companies in integrated care models.This article begins by describing the history and principles of PT­A and the role of work stress in the development of psychological and psychosomatic disorders. The implementation of PT­A is then outlined using two examples. Finally, the current study "Early Intervention at the Workplace" ("Frühe Intervention am Arbeitsplatz" [friaa]), to which several articles in this special issue refer, is briefly presented.

Utilization of Mental Health Provision, Epistemic Stance and Comorbid Psychopathology of Individuals with Complex Post-Traumatic Stress Disorders (CPTSD)-Results from a Representative German Observational Study.

Background: Complex post-traumatic stress disorder (CPTSD) is a severely debilitating recently added symptom cluster in the International Classification of Diseases (ICD-11). So far, only limited information on mental health treatment-uptake and -satisfaction of individuals with CPTSD is available. The aim of this study is to investigate these aspects in a representative sample of the German general population. Methods: Participants completed the International Trauma Questionnaire (ITQ) to identify participants with CPTSD, as well as questionnaires on mental health treatment uptake and satisfaction, adverse childhood experiences, anxiety, depression, working ability, personality functioning, and epistemic trust. Results: Of the included n = 1918 participants, n = 29 (1.5%) fulfilled the criteria for CPTSD. Participants with CPTSD had received mental health treatment significantly more often than participants with PTSD or depression (65.5% vs. 58.8% vs. 31.6%; p = 0.031) but reported significantly less symptom improvement (52.9% vs. 78.0% vs. 80.0%; p = 0.008). Lower levels of epistemic trust were associated with higher CPTSD symptoms (p < 0.001). Conclusions: Our study shows that while the vast majority of individuals with CPTSD had received mental health treatment, subjective symptom improvement rates are not satisfactory. CPTSD was associated with a broad number of comorbidities and impairments in functioning. Lower levels of epistemic trust may partially explain worse treatment outcomes.

Unconscious Activation of Negative Emotional Memories Increases Pain Unpleasantness.

OBJECTIVE: The influence of unconscious emotional processes on pain remains poorly understood. The present study tested whether cues to forgotten unpleasant images might amplify pain (i.e., in the absence of conscious recall). METHODS: Seventy-two healthy female adults (19 to 34 years) performed an adapted Think/No-think paradigm (T/NT) using 72 combinations of neutral face images (cues) paired with 36 neutral and 36 unpleasant images. After completion of the T/NT task, cues associated with forgotten neutral or unpleasant images were identified. Cues to either neutral or unpleasant images from the NT condition were then presented in randomized order while participants received intermediate-level thermal pain stimulation on the left hand. Ratings of both pain intensity and unpleasantness were acquired after each trial. RESULTS: Mean pain unpleasantness ratings were greater during presentation of cues to forgotten negative versus neutral images (5.52 [SD = 2.06] versus 5.23 [SD = 2.10]; p = .02). This pattern was also present when comparing cues to remembered negative versus neutral images (5.62 [SD = 1.94] versus 5.04 [SD = 1.90]; p < .001). Mean pain intensity ratings were higher for cues to negative versus neutral images when remembered (5.48 [SD = 1.79] versus 5.00 [SD = 1.69]; p < .001), but not when forgotten (5.27 [SD = 1.96] versus 5.16 [SD = 1.93]; p = .30). CONCLUSIONS: Using an adapted T/NT-Pain paradigm, this study demonstrated that cues to nonrecallable (but potentially unconsciously activated) negative emotional memories amplify pain unpleasantness, similar to known effects of conscious negative emotions.

Addressing psychosocial needs in patients with Long-COVID (PsyLoCo-Study): study protocol of a pilot-study of a specialized modular intervention.

Introduction: After an acute infection with the corona virus 10-20% of those affected suffer from ongoing or new symptoms. A causal therapy for the phenomenon known as Long/Post-COVID is still lacking and specific therapies addressing psychosocial needs of these patients are imperatively needed. The aim of the PsyLoCo-study is developing and piloting a psychotherapeutic manual, which addresses Long/Post-COVID-related psychosocial needs and supports in coping with persistent bodily symptoms as well as depressive or anxiety symptoms. Methods and analysis: This pilot trial implements a multi-centre, 2-arm (N=120; allocation ratio: 1:1), parallel group, randomised controlled design. The pilot trial is designed to test the feasibility and estimate the effect of 1) a 12-session psychotherapeutic intervention compared to 2) a wait-list control condition on psychosocial needs as well as bodily and affective symptoms in patients suffering from Long/Post-COVID. The intervention uses an integrative, manualized, psychotherapeutic approach. The primary study outcome is health-related quality of life. Outcome variables will be assessed at three timepoints, pre-intervention (t1), post-intervention (t2) and three months after completed intervention (t3). To determine the primary outcome, changes from t1 to t2 are examined. The analysis will be used for the planning of the RCT to test the efficacy of the developed intervention. Discussion: The pilot study will evaluate a 12-session treatment manual for Long/Post-COVID sufferers and the therapy components it contains. The analysis will provide insights into the extent to which psychotherapeutic treatment approaches improve the symptoms of Long/Post-COVID sufferers. The treatment manual is designed to be carried out by psychotherapists as well as people with basic training in psychotherapeutic techniques. This approach was chosen to enable a larger number of practitioners to provide therapeutic support for Long/Post-COVID patients. After completion of the pilot study, it is planned to follow up with a randomized controlled study and to develop a treatment guideline for general practitioners and interested specialists. Trial registration: The pilot trial has been registered with the German Clinical Trials Register (Deutsches Register Klinischer Studien; Trial-ID: DRKS00030866; URL: https://drks.de/search/de/trial/DRKS00030866) on March 7, 2023.

Improving Well-Being and Fostering Health-Oriented Leadership among Leaders in Small and Medium-Sized Enterprises (SMEs): A Systematic Review.

Leaders of small and medium-sized enterprises (SMEs) are often confronted with specific burdens, which frequently result in increased levels of stress. Leadership behaviour, in turn, has a significant impact on employees' health and performance. Using the Population, Intervention, Comparison, Outcome (PICO) method, we conducted a systematic literature search covering publications from 2002 to 2023 using PubMed, PsycInfo and Business Source Premier on stress-reducing and well-being-improving interventions for SME leaders. The Effective Public Health Practice Project (EPHPP) Quality Assessment Tool was used to assess the methodological quality and risk of bias of the included studies regarding selection bias, study design, confounders, blinding, data collection, withdrawal and drop-out. Of the 3150 identified publications, 6 were included after screening. The studies varied in content (cognitive behavioural therapy [CBT]-based, psychoeducation, and mixed interventions) and approach (individual- and organisation-centred). Not all of the examined interventions provided significant outcomes. However, CBT-based and individualised approaches showed a positive trend in reducing SME leaders' psychosocial stress and improving their well-being. Despite the limited data, it can be concluded that such interventions are beneficial for leaders and their specific needs. Future research should focus on tailored approaches, derived from well-founded theories and integrative interventions addressing SME leaders.

What helps hospital staff in times of crisis: qualitative results of a survey on psychosocial resources and stressors in German hospitals during the COVID-19 pandemic.

Background: Even before the COVID-19 pandemic, hospital workers faced a tremendous workload. The pandemic led to different and additional strain that negatively affected the well-being of employees. This study aims to explore psychosocial resources and strategies that were used by hospital staff. Methods: In the context of an intervention study, employees of three German hospitals were questioned in writing in summer and fall 2020. Five open-ended questions about the pandemic were asked to capture corresponding effects on daily work routine. Answers of 303 participants were evaluated using structuring qualitative content analysis. Results: Significant stressors and resources were identified in the areas of work content and task, social relations at work, organization of work, work environment and individual aspects. Stressors included, for example, emotional demands, conflicts, an increased workload, time and performance pressure. Important resources mentioned were, among others, the exchange with colleagues and mutual support. Sound information exchange, clear processes and guidelines and a positive work atmosphere were also important. In addition, the private environment and a positive mindset were perceived as helpful. Conclusion: This study contributes to a differentiated understanding of existing psychosocial resources of hospital staff in times of crisis. Identifying and strengthening these resources could reduce stress and improve well-being, making hospital staff better prepared for both normal operations and further crisis situations.

Effect of the addition of a mental health specialist for evaluation of undiagnosed patients in centres for rare diseases (ZSE-DUO): a prospective, controlled trial with a two-phase cohort design.

Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome. Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design. From October 1, 2018 to September 30, 2019, participants were allocated to standard care (SC, N = 684), and from October 1, 2019 to January 31, 2021 to innovative care (IC, N = 695). The cohorts consisted mainly of adult participants with only a minority of children included (N = 67). IC included the involvement of a mental health specialist in all aspects of care (e.g., assessing medical records, clinic visits, telehealth care, and case conferences). Clinicaltrials.gov identifier: NCT03563677. Findings: The proportion of patients with diagnoses established within 12 months after the first visit to the CRD explaining the entire symptomatology (primary outcome) was 19% (N = 131 of 672) in the SC and 42% (N = 286 of 686) in the IC cohort (OR adjusted for centre effects 3.45 [95% CrI: 1.99-5.65]). The difference was mainly due to a higher prevalence of mental disorders and non-rare somatic diseases in the IC cohort. The median time to explaining diagnoses was one month shorter with IC (95% CrI: 1-2), and significantly more patients could be referred to local regular care in the IC (27.5%; N = 181 of 659) compared to the SC (12.3%; N = 81 of 658) cohort (OR adjusted for centre effects 2.70 [95% CrI: 2.02-3.60]). At 12-month follow-up, patient satisfaction with care was significantly higher in the IC compared to the SC cohort, while quality of life was not different between cohorts. Interpretation: Our findings suggested that including a mental health specialist in the entire evaluation process of CRDs for undiagnosed adolescents and adults should become an integral part of the assessment of individuals with a suspected rare disease. Funding: The study was funded by the Global Innovation Fund from the Joint Federal Committee in Germany (Innovationsfonds des Gemeinsamen Bundesausschusses), grant number 01NVF17031.

[Working in a team and mental health]. / Arbeit im Team und psychische Gesundheit.

Humans have always naturally lived in groups, which has a significant impact on the well-being and mental stability of the individual. Various physiological processes are coregulated via the closeness of other persons. About one third of our adulthood is spent at work where social relationships often play an important role, because we are typically working with other individuals in groups or a team. In these situations, mutual support and successful cooperation can develop, which promotes the mental and physical health of the employees of a company ("social capital"). From various perspectives it becomes obvious that the quality of relationships at the workplace is a key factor for the satisfaction and health of individual employees as well as for the cohesion, resilience and performance of the entire team. This is confirmed by empirical findings that still need to be expanded, especially with respect to the neurobiological associations of the cooperation in teams and individual health.

Smartphone and Instagram use, body dissatisfaction, and eating disorders: investigating the associations using self-report and tracked data.

BACKGROUND: Previous research has linked smartphone and Instagram use to higher body dissatisfaction (BD) as well as eating disorder (ED) symptomatology. However, these studies have typically been limited to using self-report measures for technology use which, as shown by scientific literature, might not be reliable. In the present work, we combine self-reported assessments as well as tracked smartphone and Instagram use. METHODS: The effective sample comprised N = 119 women (34 with ED diagnosis history) who were queried about BD and ED symptomatology, and who provided the data about their smartphone and Instagram use duration for each day of the previous week. RESULTS: The study results show that women with an ED diagnosis history scored higher on both BD as well as ED scales. Although women with an ED diagnosis history had higher smartphone screen time, there were no statistically significant differences in Instagram screen time. Tracked smartphone use duration was positively correlated with both BD and ED symptomatology, but the role of Instagram use needs to be further elucidated. CONCLUSIONS: The results of this study show that while BD and ED symptomatology are correlated with smartphone use, it may be that Instagram use is not the main contributor to that relationship.

The multicenter effectiveness study of inpatient and day hospital treatment in departments of psychosomatic medicine and psychotherapy in Germany.

Background: Reliable outcome data of psychosomatic inpatient and day hospital treatment with a focus on psychotherapy are important to strengthen ecological validity by assessing the reality of mental health care in the field. This study aims to evaluate the effectiveness of inpatient and day hospital treatment in German university departments of Psychosomatic Medicine and Psychotherapy in a prospective, naturalistic, multicenter design including structured assessments. Methods: Structured interviews were used to diagnose mental disorders according to ICD-10 and DSM-IV at baseline. Depression, anxiety, somatization, eating disorder and posttraumatic stress disorder (PTSD) symptoms, as well as personality functioning were assessed by means of questionnaires on admission and at discharge. Results: 2,094 patients recruited by 19 participating university hospitals consented to participation in the study. Effect sizes for each of the outcome criteria were calculated for 4-5 sub-groups per outcome domain with differing severity at baseline. Pre-post effect sizes for patients with moderate and high symptom severity at baseline ranged from d = 0.78 to d = 3.61 with symptoms of PTSD, depression, and anxiety showing the largest and somatization as well as personality functioning showing somewhat smaller effects. Conclusions: Inpatient and day hospital treatment in German university departments of Psychosomatic Medicine and Psychotherapy is effective under field conditions. Clinical trial registration: https://drks.de/search/de/trial/DRKS00016412, identifier: DRKS00016412.

The prevalence of effort-reward imbalance and its associations with working conditions, psychosocial resources and burden among health care workers during the COVID-19 pandemic: Results of the egePan-Voice study.

OBJECTIVE: The association between a measure of effort-reward imbalance (ERI) and profession as well as gender in a sample of health care workers (HCW) during the first wave of the COVID-19 pandemic in Germany using the egePan-Voice study. In addition, we examined, which factors are associated with an effort-reward imbalance ratio (ERI ratio) >1. METHODS: In a large sample of HCW (N = 6174) we assessed occupational stress with the short version of the effort-reward imbalance (ERI) questionnaire, working conditions, COVID-19-related problems and psychosocial resources (ENRICHD Social Support Inventory, ESSI; Sense of Coherence Scale, SOC-3 and optimism, SOP2). RESULTS: The prevalence of a ERI ratio >1 among HCW was 50.9%. The prevalence's of an ERI ratio >1 were statistically significant different between gender as well as the occupational profession. The proportion of women (51.8%) with ERI ratio >1 was significantly higher than among men (47.8%). The highest ERI imbalance was found among nurses (62.8%), followed by medical technical assistants (MTA) (58.8%), while psychologists/psychotherapists revealed the lowest value (37.8%), followed by physicians (41.8%). In the total sample, most essential factors reported at this time for increased ERI ratio were: insufficient staff for the current work load, insufficient recovery, feeling insufficiently protected by measures taken by the hospital/the employer, high occupancy rate of the wards, insufficient trust in colleagues and being a nurse as compared with being a physician. CONCLUSION: The findings indicate a high proportion of HCW with effort-reward imbalance and substantial profession-related differences. Preventive interventions should be offered to vulnerable groups among the HCW to decrease the imbalance measured by work stress.

The transformation of masculinity orientations and work-related attitudes in men treated for depression (TRANSMODE): study protocol for a mixed-methods observational study.

BACKGROUND: Masculinity norms play a crucial role in men's help-seeking behaviors, service-use, and coping strategies for depression. While previous studies provided evidence for the association between gender role orientations, work related attitudes, stigmatization of men with depression and depressive symptoms, it remains unclear to what extent gender role orientations change over time and whether psychiatric and psychotherapeutic treatment have an impact on these transformations. Additionally, the role of partners in supporting depressed men and the impact of dyadic coping on these processes have not been explored. The aim of this study is to investigate how masculinity orientations and work-related attitudes change over time in men treated for depression, and to examine the role of their partners and dyadic coping in these transformation processes. METHODS: TRANSMODE is a prospective longitudinal mixed-methods study investigating the transformation of masculinity orientations and work-related attitudes in men treated for depression between the ages of 18 and 65 from different settings in Germany. The study will recruit 350 men from various settings for quantitative analysis. By applying a latent transition analysis, the primary outcome are changes in masculine orientations and work-related attitudes over time, measured at four times (t0, t1, t2, t3) with intervals of 6 months. Qualitative interview with a subsample of depressed men selected using latent profile analysis, will be conducted between t0 and t1 (a1) with a follow-up of 12 months (a2). In addition, qualitative interviews with the partners of depressed men will be conducted between t2 and t3 (p1). Qualitative data will be analysed using qualitative structured content analysis. DISCUSSION: A comprehensive understanding of the transformation processes of masculinity orientations over time including the impact of psychiatric/psychotherapeutic treatment and the role of partners can lead to the development of gender-sensitive depression treatment tailored to the unique needs of men with depression. Thus, the study can promote more effective and successful treatment outcomes and further contribute to reducing the stigma surrounding mental health issues among men and encourage them for mental health service use. TRIAL REGISTRATION: This study is registered in the German Clinical Trail Register (DRKS) and the WHO International Clinical Trials Registry Platform (ICTRP) under registration number DRKS00031065 (Date of registration 06 February 2023).

COVID-19 vaccination exacerbates ex vivo IL-6 release from isolated PBMCs.

Ex vivo culturing of isolated PBMCs from individuals vaccinated with the coronavirus disease 2019 (COVID-19) vaccine BNT162b1 revealed a pronounced T cell response in the presence of the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The latter was 10-fold more pronounced than the ex vivo response of PBMCs from the same individuals to other common pathogen T cell epitope pools, suggesting COVID-19 vaccination to induce RBD-specific T cell responses and not to facilitate T cell (re)activity in general. In the current study we investigated whether COVID-19 vaccination long-lastingly affects plasma interleukin (IL)-6 concentrations, complete blood counts, ex vivo IL-6 and IL-10 secretion of PBMCs cultured under basal conditions or in the presence of concanavalin (Con) A and lipopolysaccharide (LPS), salivary cortisol and α-amylase, mean arterial pressure (MAP), heart rate (HR) as well as mental and physical health status. The study was initially designed to investigate whether the presence vs. absence of own pets during urban upbringing has protective effects against psychosocial stress-induced immune activation during adulthood. However, as COVID-19 vaccines were approved while the study was ongoing and as, therefore, both vaccinated and non-vaccinated individuals have been recruited, we were able to stratify our data set with respect to the COVID-19 vaccination status and to assess the long-lasting effects of COVID-19 vaccination on physiological immunological, cardiovascular and psychosomatic health parameters. This data is presented in the current study. We show that isolated PBMCs from individuals vaccinated against COVID-19 show a ~ 600-fold increase in basal and a ~ 6000-fold increase in ConA-induced proinflammatory IL-6 secretion, and a ~ 2-fold increase in basal and ConA-induced antiinflammatory IL-10 secretion, both in comparison with non-vaccinated individuals. In contrast, LPS-induced ex vivo IL-6 and IL-10 secretions were not affected by vaccination status, as were plasma IL-6 concentrations, complete blood counts, salivary cortisol and α-amylase, cardiovascular measures and psychosomatic health. In summary, our findings are of relevance for many clinical studies ran before/during the pandemic, clearly indicating that consideration of participants' vaccination status is critical, at least when assessing ex vivo PBMC functionality.

Neutrophil-derived catecholamines mediate negative stress effects on bone.

Mental traumatization is associated with long-bone growth retardation, osteoporosis and increased fracture risk. We revealed earlier that mental trauma disturbs cartilage-to-bone transition during bone growth and repair in mice. Trauma increased tyrosine hydroxylase-expressing neutrophils in bone marrow and fracture callus. Here we show that tyrosine hydroxylase expression in the fracture hematoma of patients correlates positively with acknowledged stress, depression, and pain scores as well as individual ratings of healing-impairment and pain-perception post-fracture. Moreover, mice lacking tyrosine hydroxylase in myeloid cells are protected from chronic psychosocial stress-induced disturbance of bone growth and healing. Chondrocyte-specific ß2-adrenoceptor-deficient mice are also protected from stress-induced bone growth retardation. In summary, our preclinical data identify locally secreted catecholamines in concert with ß2-adrenoceptor signalling in chondrocytes as mediators of negative stress effects on bone growth and repair. Given our clinical data, these mechanistic insights seem to be of strong translational relevance.

The PMN-MDSC - A key player in glucocorticoid resistance following combined physical and psychosocial trauma.

Stress-associated somatic and psychiatric disorders are often linked to non-resolving low-grade inflammation, which is promoted at least in part by glucocorticoid (GC) resistance of distinct immune cell subpopulations. While the monocyte/macrophage compartment was in the focus of many clinical and preclinical studies, the role of myeloid-derived suppressor cells (MDSCs) in stress-associated pathologies and GC resistance is less understood. As GC resistance is a clear risk factor for posttraumatic complications in patients on intensive care, the exact interplay of physical and psychosocial traumatization in the development of GC resistance needs to be further clarified. In the current study we employ the chronic subordinate colony housing (CSC) paradigm, a well-characterized mouse model of chronic psychosocial stress, to study the role of myeloid cells, in particular of MDSCs, in innate immune activation and GC resistance following combined psychosocial and physical (e.g., bite wounds) trauma. Our findings support the hypothesis that stress-induced neutrophils, polymorphonuclear (PMN)-MDSCs and monocytes/monocyte-like (MO)-MDSCs get primed and activated locally in the bone marrow as determined by toll-like receptor (TLR)2 upregulation and increased basal and lipopolysaccharide (LPS)-induced in vitro cell viability. These primed and activated myeloid cells emigrate into the peripheral circulation and subsequently, if CSC is accompanied by significant bite wounding, accumulate in the spleen. Here, PMN-MDSCs and monocytes/MO-MDSCs upregulate TLR4 expression, which exclusively in PMN-MDSCs promotes NF-κB hyperactivation upon LPS-stimulation, thereby exceeding the anti-inflammatory capacities of GCs and resulting in GC resistance.