Panic attacks are characterized by intense feelings of uncontrollable threat and induce experiences of intense stress. As one of the major physiological stress systems of the body, the hypothalamic-pituitary-adrenocortical axis (HPA) may be a key to our understanding of a biological basis of this anxiety disorder. While recent studies have found evidence for short-term HPA changes in panic disorder with flattened cortisol responses to stimulation, no data have been available on tonic, i.e., long-term HPA activity in these patients. The current study therefore investigated the cumulative cortisol incorporation in hair over the period of three months in patients with panic disorder (n = 45) and healthy individuals (n = 45). Results showed higher hair cortisol concentration in patients with panic disorder compared to healthy controls. The duration and the severity of the disorder was unrelated to hair cortisol concentrations. In subsample analyses, patients with panic disorder and comorbid depression showed no significant differences in hair cortisol concentration compared to patients with pure panic disorder. The present findings do not support to the notion that a hypoactive HPA axis may be an important biological feature of patients suffering from panic disorder. Future studies will have to show in a large sample whether a changed HPA axis reactivity is present and causally related to the development and course of the disorder.

Abstract Background Sexual dysfunctions in individuals with social anxiety disorder (SAD) have been previously reported. However, most of these results refer to physical and behavioral measures. Psychological aspects have not been previously researched. Method In the present study, we utilized an online version of the “Multidimensional Sexuality Questionnaire” (MSQ) in a sample of individuals with SAD (n = 242, 40.70 ± 13.40 years, 58.7% female). We hypothesized greater difficulties for SAD individuals compared to controls without SAD through the influence of fear and avoidance symptoms. Results Based on multivariate analyses (MANCOVA), SAD individuals showcased significant deficiencies in almost all subscales of the MSQ compared to the control group (partial η2 = 0.016 − 0.217, all p < .001). Moreover, men with SAD were significantly more preoccupied and motivated for sexual behaviour and relationships than women with SAD (partial η2 = 0.104 − 0.159, all p < .001). Conclusion These results give first insights for psychological reasons possibly underlying sexual difficulties in SAD patients. SAD individuals spend less time thinking about and are less motivated for sexuality. Assertiveness and the belief of one’s control and autonomy of sexuality are less pronounced in SAD individuals. Those signs can be approached via different techniques and therapeutic interventions if difficulties with sexuality and sexual satisfaction are relevant for those affected by SAD. Clinical trial number Not applicable.

Abstract Interleukin-17A (IL-17A) has been implicated in stress- and pain-related inflammation, yet evidence for acute IL-17A stress response in humans remains scarce. This study examined whether the Maastricht Acute Stress Test (MAST) induces changes in circulating IL-17A and how IL-17A dynamics relate to cortisol and subjective stress/pain. Forty-six healthy adults (mean age: 30.50 ± 12.86 years; 54% female) completed the standardized MAST. Serum IL- 17A and cortisol were assessed repeatedly across baseline and recovery. Stress- and pain- related ratings (VAS) and trait questionnaires (e.g., chronic stress, psychological distress, resilience) were completed. There was a significant increase over time in IL-17A and cortisol following the MAST, with an 36 % increase of IL-17A level measured at 105 min post- stressor and cortisol peaking at 10 min post-stressor. IL-17A indices (baseline and AUCi) showed no meaningful associations with cortisol, subjective stress/pain, or psychological traits, whereas cortisol response (AUCi) correlated positively with perceived acute stress and pain. Overall, the MAST produced clear IL-17A and cortisol responses that appeared dissociable in healthy individuals. Future studies should include broader inflammatory panels and clinical or high-stress samples to clarify conditions under which IL-17A covaries with HPA-axis activity and subjective experience.

Social anxiety disorder (SAD) is a common anxiety disorder (ANX) with moderate heritability that often co-occurs with other mental disorders. Until now, sample sizes in genetic analyses of SAD have been limited, so that the genetic basis of SAD and its subphenotypes is still largely unknown. In a large cohort comprising n = 1,194 SAD patients derived from five German cohorts and n = 3,409 controls from the Heinz Nixdorf Recall Study, we computed polygenic risk scores (PRS) at six p-thresholds using PRSice-2 based on large-scale genome-wide association studies for depression, major depressive disorder (MDD), ANX, schizophrenia (SCZ), bipolar disorder (BD), attention-deficit/hyperactivity disorder (ADHD), anorexia nervosa (AN), autism spectrum disorder (ASD), and alcohol dependence (AD). We used general linear models to examine the association between the PRS and SAD status. In SAD subsamples, we investigated whether the PRS are associated with SAD subphenotypes (i.e., SAD severity, current depressive symptoms, comorbid MDD) using correlation analyses and a general linear model. Results were corrected for multiple testing. The SAD status was significantly associated with PRS for depression, MDD, ANX, SCZ, BD, AN, and ASD (pBH-adjusted<0.05), but not with PRS for ADHD and AD. In SAD subsamples, the subphenotype analyses revealed no significant associations after correction for multiple testing (pBH-adjusted>0.05). Our results support that SAD seems to be genetically highly overlapping with other mental disorders, which might underline a common psychopathological factor. No significant association was found with SAD severity, current depressive symptoms or comorbid MDD. A better understanding of the genetic architecture of SAD may help to develop new diagnostic and treatment approaches.

Skeletal muscle radiodensity (SMD) is an emerging imaging-derived marker of muscle quality. Its prognostic relevance in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy has not yet been systematically evaluated. This study aims to investigate the prognostic value of SMD derived from routine pretherapeutic PET/CT imaging in a large real-world mCRPC cohort treated with [¹⁷⁷Lu]Lu-PSMA-617. In this single-center study, the largest to date cohort comprising 410 mCRPC patients was analyzed. SMD was quantified automatically from the L3-level CT component of pretherapeutic [⁶⁸Ga]Ga-PSMA-PET/CT using an AI-based segmentation tool. An optimal SMD cut-off (19.26 HU) was determined for survival stratification. Associations with overall survival (OS) were assessed using multivariable Cox regression (univariable and multivariable, adjusted for baseline PSA) and Kaplan-Meier analysis. Lower SMD was associated with reduced OS (HR 1.87, P<.001). Median OS were significantly shorter in the SMD-low group compared to the SMD-high group (7.6 months vs. 12.2 months; P<.001). This prognostic stratification was seen in both, patients with or without PSA50 or PSA90 response, respectively. SMD correlated with age, albumin, and PSA, but not with BMI. SMD assessed from routine pretherapeutic PET/CT is a non-invasive prognostic biomarker in patients undergoing PSMA-targeted radioligand therapy. Integration of host-derived imaging biomarkers such as SMD with tumor-specific parameters may improve risk stratification, prehabilitation and support future individualized treatment strategies in advanced prostate cancer.

The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder and phobias) are highly prevalent, often onset early and cause substantial global disability. Although distinct in their clinical presentations, they probably represent differential expressions of a dysregulated threat-response system. Here, we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 out of the 58 associations replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism implicated in ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.

Demoralization represents a clinical syndrome conceptualized as maladaptive coping to a stressor associated with discouragement, feelings of hopelessness, helplessness, and a loss of meaning in life. It is a prevalent comorbidity in individuals with severe physical illnesses and affects a substantial proportion of the general population when facing global stressors like the COVID-19 pandemic. The main aim of the study was to test whether demoralization and features of depression and anxiety might reflect distinct entities within the general population, specifically in older adults, and to explore symptom interconnections, using a network psychometrics approach. The revised demoralization scale (DS-II) and the patient health questionnaire 4 (PHQ-4) were applied to a representative sample (N = 2434) from the German general population. Network structures were analyzed using exploratory graph analysis (EGA) to identify the most distinct symptom groupings and their relationships. Stability of networks and symptom groupings was tested using bootstrap procedures. EGA revealed unidimensionality within younger adulthood and a four-factor solution within older adults, reliably distinguishing PHQ-4 and DS-II items. The most central features of the network were worthlessness, pointlessness, helplessness, feeling trapped and low mood. Suicidal ideation was more closely related to DS-II worthlessness than to PHQ-4 items. The cross-sectional design and using PHQ-4 instead of more comprehensive measures of depression and anxiety were limitations. In conclusion, in general population, demoralization symptoms can be distinguished from lack of interest or pleasure and low mood. It might represent a valid psychological construct beyond clinical populations. Further investigation of diagnostic implications is encouraged.

Uterine fibroids often lead to symptoms that negatively impact health-related quality of life (HRQOL). High-intensity focused ultrasound (HIFU) has emerged as a promising noninvasive treatment for reducing fibroid size and symptoms. The Mirabilis system for ultrasound (US)-guided HIFU introduces a novel technique known as ‘shell ablation’. This study evaluates the feasibility and efficacy of Mirabilis in a clinical setting, focusing on clinical outcomes. Sixteen patients with 23 uterine fibroids were treated with the Mirabilis system. Follow-up assessments included US and MRI at baseline, 6 weeks, 3, 6 and 9 months, and 1 year after HIFU. Changes in symptoms and QOL were evaluated using the Uterine Fibroid Symptom and HRQOL Questionnaire. A significant reduction in fibroid volume was observed after HIFU (baseline 182.1 ± 49.3 ml; 1 year: 76.0 ± 37.9 ml, p < 0.001). The symptom severity score significantly declined (baseline 57.2 ± 3.8; 1 year: 30.2 ± 4.9, p < 0.001), correlating with a significant improvement in HRQOL (baseline 47.0 ± 3.9, 1 year: 71.8 ± 5.3, p < 0.001). HIFU with the portable Mirabilis system is a feasible and safe noninvasive treatment for symptomatic uterine fibroids in an outpatient setting. This approach allows efficient and rapid ablation even for large fibroids, significantly reducing fibroid volume and symptoms.

OBJECTIVES:This study aimed to examine the stability of trait resilience and identify factors influencing its change during inpatient psychosomatic psychodynamic psychotherapy. METHODS:A total of 225 patients undergoing inpatient treatment at the University Hospital Münster completed the Resilience Scale-13 (RS-13) at admission and discharge. Additional questionnaires assessed childhood trauma (CTQ), sense of coherence (SOC-13), and health-related quality of life (EQ-5D-3L). A linear mixed model evaluated changes in resilience and influencing factors. RESULTS:Resilience scores significantly increased from admission to discharge (Estimate = 12.10, SE = 3.96, t(224) = 3.06, p = 0.002). Lower health-related quality of life at admission was associated with greater resilience improvements during therapy (Estimate = -2.05, SE = 0.48, t(224) = -4.27, p < 0.001). Higher sense of coherence at admission was strongly linked to higher trait resilience overall (Estimate = 0.59, SE = 0.05, t(224) = 11.80, p < 0.001). Childhood trauma exhibited a significant interaction with therapy time point (Estimate = 0.19, SE = 0.05, t(224) = 4.01, p < 0.001), suggesting individuals with more childhood trauma experiences showed greater resilience improvements. Gender and age were not significant predictors. Hospitalization duration had a small negative association with resilience change (Estimate = -0.05, SE = 0.02, t(224) = -1.98, p = 0.048). CONCLUSIONS:Inpatient psychosomatic psychotherapy effectively enhances trait resilience. Higher sense of coherence, poorer initial health-related quality of life, and more severe childhood trauma experiences significantly predicted greater resilience improvements. These findings highlight the importance of promoting resilience as a central therapeutic goal.

Demoralization refers to a mental state of poor coping characterized by a loss of purpose and meaning, feelings of hopelessness and worthlessness, and suicidal ideation. The revised demoralization scale (DS-II) is among the most frequently used self-report measures. Recently, the psychometric properties and normative values of the DS-II-Ms (Münster version of the DS-II) were published, alongside a validation study linking it to depression and anxiety in the general population. This study investigates the relationship between DS-II-Ms scores and resilience, as well as well-validated trait resilience factors, specifically locus of control and general self-efficacy, using a network psychometrics approach. DS-II-Ms, Patient Health Questionnaire 2 (PHQ-2), Generalized Anxiety Disorder Scale 2 (GAD-2), Internal-External Locus of Control Short Scale-4 (IE4), General Self-Efficacy Short Scale-3 (GSE-3) and Brief Resilience Scale (BRS) were applied to a representative sample (N = 2401) of the German general population. A gaussian graphical model was estimated using a non-regularized algorithm to depict the unique connections between the measures. DS-II-Ms was moderately associated with lower internal (and higher external) locus of control while being conditionally independent from BRS and GSE-3. Conversely, depression symptoms lack of interest/low mood were connected to resilience and general self-efficacy but conditionally independent from locus of control. Although the cross-sectional study design limits directional interpretation, our findings indicate that trait resilience measures have unique associations with demoralization and depression/anxiety symptoms, supporting the discriminant validity of the demoralization construct. Depressed and demoralized individuals might benefit from different therapeutical approaches, targeting specific resilience factors.

The present study investigates the concentrations of the endocannabinoids under standardized psychosocial stress induction (TSST) and a resting condition in healthy males. Hereby, all endocannabinoids were analyzed under a standardized laboratory procedure (arachidonic acid (AA), arachidonoylethanolamide (AEA), isomeres 2-AG arachidonoylglycerol (2-AG) and palitoylethanolamide (PEA)). A total of n = 32 healthy controls (HC) were included in the study. The participants were exposed to the Trier Social Stress Test (TSST) for reliable laboratory stress induction and under rest. Blood samples were taken during the TSST by an intravenous catheter to examine the endocannabinoid (eCB) stress response. There were no significant differences in baseline levels of the parameters between the TSST and the resting condition (p´s > 0.28). ANOVA results indicated a significant effect of time over the six measurements points in all parameters. In the parameter 2-AG and AA a strongly, and in AEA a slightly, significant effect of condition*time could be unveiled. In conclusion, the present study showed that acute psychosocial stress increases plasma endocannabinoids. Further research is required to evaluate the endocannabinoid system in different anxiety disorders to elucidate which patients might benefit from eCB-based therapy.

There is limited clarity in the research regarding sex-specific differences in Social Anxiety Disorder (SAD). To address this gap, the current study focuses on examining sex-specific differences in sociodemographic factors and clinical impairment, as well as parenting behavior. The sample consisted of 425 women (39.0 ± 14.3 years) and 283 men (43.0 ± 14.0 years), all SCID-diagnosed with SAD. Both groups were compared regarding SAD symptom severity (Social Phobia Inventory; SPIN), comorbidities, current partnerhip, level of education and clinical impairment (suicidal thoughts, psychotherapeutic/psychiatric treatment, psychopharmacology). Women with SAD reported significantly higher SAD symptom severity. The two groups also differed regarding comorbidities: Women reported significantly more comorbid depressive disorders whereas men reported significantly more comorbid alcohol abuse or dependence and substance-related disorders. No sex-specific differences were found in partnership status, educational attainment or clinical impairment. Regarding the prediction of SAD symptom severity by parenting styles, high paternal affectionless control was a significant predictor in women. In men, high paternal affectionless control as well as high paternal affectionate constraint emerged as significant predictors. The findings of our study highlight the importance of the paternal affectionless control style as a consistent predictor of SAD symptom severity across both women and men. These results have clinical implications for the therapeutic treatment of SAD and societal implications in challenging outdated, traditional gender roles.

Background Bodily distress is highly prevalent in the adult population and those affected exhibit a decreased quality of life (QoL). What contributes to this decreased QoL is incompletely understood. As bodily distress has been associated both with comorbidities and alterations in emotion regulation, in particular anger suppression, the relation between suppressed anger, psychopathology and QoL was studied. Methods In a cross-sectional study of adult psychosomatic outpatients presenting with bodily distress classified as somatoform disorders, anger suppression (Anger-In scale from the State-Trait Anger Expression Inventory), psychopathology (Symptom Checklist 90-R) and QoL (short version of the World Health Organization's Quality of Life Questionnaire) were assessed. Firstly, the association between anger suppression and different domains of QoL was examined. Secondly, mediation analyses were employed to test whether the relationship between anger suppression and QoL was mediated by the level of psychopathological symptoms. Results Data from 539 patients (63.1 % female, mean age 41.3 (SD: 15) years) were analysed. Higher Anger-In was associated with decreased QoL in all four domains (p < 0.001). Mediation analysis showed a direct effect of anger suppression on decreased psychological and social QoL. For the physical and environmental domains of QoL, however, this relationship was fully mediated by psychopathology (depression, somatisation). Conclusion Anger suppression was strongly associated with decreased QoL in patients with bodily distress. While this was partly explained through basic psychopathology, there were some direct effects of anger suppression, in particular on social and psychological QoL. Anger management might hence be integrated in the treatment of bodily distress.

CONTEXT:Palliative care aims to improve the quality of life in patients with progressive diseases such as cancer. Effective cancer pain management is a major challenge of palliative treatment. Empirical data on the prevalence of cancer pain, the efficiency of pain treatment and influencing factors are scarce. OBJECTIVES:Here, we investigated pain in cancer patients treated on inpatient palliative care wards in Germany. METHODS:N = 4779 data sets provided by the German Palliative Care Registry from yearly evaluation periods between 2015 and 2020 were included. Pain ratings were assessed by professionals through a checklist of symptoms and problems (HOPE-SP-CL). RESULTS:More than half of the included patients suffered from moderate/severe pain at the beginning of inpatient palliative care and in 71% of these patients, pain relief was achieved at the end of inpatient treatment. Pain intensity, depression and ECOG performance status at admission were weak predictors of later pain relief. The highest pain intensity at the beginning and least pain relief were found in patients with bone and cartilage cancer. The highest percentage of adequate pain control (81%) was seen in 2020. CONCLUSION:Data from the German Palliative Care Registry confirmed that although increasingly better addressed over the years, insufficiently controlled cancer pain remains a challenge for palliative care units. Patient-specific (e.g. psychological comorbidity) and cancer-related (e.g. bone or cartilage cancer) risk factors for poor pain treatment underline the need for individualized multimodal pain management including psychological support.

Seltene Erkrankungen werden oft erst spät erkannt. Ihre Diagnose ist aufgrund der Diversität, Komplexität und Heterogenität klinischer Symptome besonders anspruchsvoll. Computergestützte diagnostische Hilfen, oft als „diagnostic decision support systems“ (DDSS) bezeichnet, sind vielversprechende Tools, um die Zeit bis zur Diagnose zu verkürzen. DDSS sind trotz erster positiver Evaluationen noch nicht sehr weit verbreitet, was unter anderem auf die mangelnde Integration in existierende klinische oder Praxisinformationssysteme zurückgeführt werden kann. Dieser Beitrag bietet einen Einblick in aktuell existierende DDSS, die ohne Zugriff auf elektronische Patientenakten funktionieren und nur einfach zu beschaffende Informationen benötigen. Im Rahmen einer systematischen Literaturrecherche wurden 8 Beiträge identifiziert, in denen DDSS untersucht werden, die bei der Diagnose seltener Erkrankungen unterstützen können und dabei keinen Zugriff auf elektronische Patientenakten oder andere Informationssysteme in Praxen und Kliniken verlangen. Die wichtigsten Vor- und Nachteile der identifizierten Systeme zur Unterstützung bei der Diagnostik seltener Erkrankungen wurden extrahiert und zusammenfassend dargestellt. Symptom-Checker sowie DDSS auf Basis von Porträtfotos und Schmerzzeichnungen existieren bereits. Der Reifegrad dieser Anwendungen ist unterschiedlich. DDSS stehen aktuell noch vor einigen Herausforderungen – so gibt es Bedenken zu Datenschutz und Genauigkeit, zudem sind die Akzeptanz und Bekanntheit noch eher gering. Dem gegenüber steht ein großes Potenzial für eine schnellere Diagnosestellung, insbesondere bei seltenen Erkrankungen, die aufgrund ihrer großen Anzahl und geringen Bekanntheit leicht übersehen werden. Der Einsatz von DDSS sollte daher von Ärztinnen und Ärzten im Einzelfall gut abgewogen werden.