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Aim: Most prediction models for coronary artery disease (CAD) compile biomedical and behavioural risk factors, using linear multivariate models. This study explored the potential of integrating positive psychosocial factors (PPFs), including happiness, satisfaction with life, and social support, into conventional and machine learning-based CAD prediction models., Methods: We included UK Biobank participants without CAD at baseline. First, we estimated associations of individual PPFs with subsequent acute myocardial infarction (AMI) and chronic ischaemic heart disease (CIHD) using logistic regression. Then, we compared the performances of logistic regression and eXtreme Gradient Boosting (XGBoost) prediction models when adding PPFs as predictors to the Framingham Risk Score (FRS)., Results: Based on a sample size between 160,226 and 441,419 of UK Biobank participants, happiness, satisfaction with health and life, and participation in social activities were linked to lower AMI and CIHD risk (all p-for-trend ≤ 0.04), while social support was not. In a validation sample, adding PPFs to the FRS using logistic regression and XGBoost prediction models improved neither AMI (AUC change: 0.02% and 0.90%, respectively) nor CIHD (AUC change: -1.10% and -0.88%, respectively) prediction., Conclusions: PPFs were individually linked to CAD risk, in line with previous studies, and as reflected by the new European Society of Cardiology guidelines on cardiovascular disease prevention. However, including available PPFs in CAD-prediction models did not improve prediction compared to the FRS alone. Future studies should explore whether PPFs may act as CAD-risk modifiers, especially if the individual's risk is close to a decision threshold., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Study Aims: During the COVID-19 pandemic, there was increasing pressure to be vaccinated to prevent further spread of the virus and improve outcomes. At the same time, part of the population expressed reluctance to vaccination, for various reasons. Only a few studies have compared the perceptions of vaccinated and non-vaccinated patients being treated in hospitals for COVID-19. Our aim was to investigate the association between vaccination status and perceived healthcare-associated discrimination in patients with COVID-19 receiving hospital treatment., Methods: Adult patients presenting to the emergency department or hospitalised for inpatient care due to or with COVID-19 from 1 June to 31 December 2021 in two Swiss hospitals were eligible. The primary endpoint was patients' perceived healthcare-associated discrimination, measured with the Discrimination in Medical Settings (DMS) scale. Secondary endpoints included different aspects of perceived quality of care and symptoms of psychological distress measured with the Hospital Anxiety and Depression Scale., Results: Non-vaccinated patients (n = 113) had significantly higher DMS scores compared to vaccinated patients (n = 80) (mean: 9.54 points [SD: 4.84] vs 7.79 points [SD: 1.85]; adjusted difference: 1.18 [95% CI: 0.04-2.33 points]) and 21 of 80 vaccinated patients felt discriminated against vs 54 of 113 non-vaccinated patients (adjusted OR: 2.09 [95% CI: 1.10-3.99 ]). Non-vaccinated patients reported lower scores regarding respectful treatment by the nursing team (mean: 8.39 points [SD: 2.39] vs 9.30 points [SD: 1.09]; adjusted difference: -0.6 [95% CI: -1.18 - -0.02 points])., Conclusion: We found an association between vaccination status and perceived healthcare-associated discrimination. Healthcare workers should act in a professional manner regardless of a patient's vaccination status; in doing so, they might prevent the creation of negative perceptions in patients.

Objective: To explore workload-related stress levels experienced by consultation liaison psychiatry (CLP) staff in England and Ireland, and factors relevant to such a burden, during the COVID-19 pandemic., Methods: Data were obtained for England and Ireland from a European survey among CLP services in general hospitals spread via CLP networks (11th June - 3rd October 2021). The heads of respective CLP services in general hospitals responded on behalf of each service, on 100 CLP hospital staff in total., Dependent Variable: workload-related stress levels in CLP services due to COVID-19 (0-10 point scale)., Independent Variables: hospital size, CLP service size, degree of hospital involvement in COVID-19-related care, and the number of support options available to hospital staff. Spearman's rho correlation analyses were performed., Results: There was a significant association between the hospital's involvement in COVID-19-related care and workload-related stress levels as reported by CLP staff: r(22) = 0.41, p = 0.045, R 2  = 0.17. There were no significant associations between workload-related stress levels and other variables including staff support (p = 0.74)., Conclusion: Our findings suggest that perceived workload-related stress levels of CLP staff during the COVID-19 pandemic can be an indicator of COVID-19 involvement of the hospitals. Staff support seemed not to alleviate work stress in the context of the pandemic. Healthcare policies should improve working conditions for CLP hospital staff that play an essential role from a population health perspective. Rigorous measures may be needed to ensure mental healthcare provision remains tenable and sustainable in the long term., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Over the last 3 years, CFC received funding for The European Platform to Promote Wellbeing and Health in the workplace (EMPOWER), a European project to reduce the impact of mental health problems at the workplace, from European Union's Horizon 2020 research and innovation program under grant agreement No 848180. She received grants from The Netherlands Organization for Health Research and Development, grant number 537001002 and 5370010021, from NIHR, grant number 132852 and COV-LT2–0043, and from the BMA, for unrelated projects. She received royalties from several publishers for books on the topic of psychiatry. She received an honorarium from Janssen for speaking at a symposium and support for giving a lecture at the Lloyds Foundation annual conference 2019. JS received funding for EMPOWER from European Union's Horizon 2020 research and innovation program under grant agreement No 848180. GM received funding from the Stanley Thomas Johnson Stiftung & Gottfried und Julia Bangerter-Rhyner-Stiftung under project no. PC 05/18, from Gesundheitsförderung Schweiz under project no. 18.191/K50001, from the Swiss Heart Foundation under project no. FF21101, from the Research Foundation of the International Psychoanalytic University (IPU) Berlin under project no. 5217, from the German Federal Ministry of Education and Research under budget item 68606, from the Hasler Foundation under project No. 23004, in the context of a Horizon Europe project from the Swiss State Secretariat for Education, Research and lnnovation (SERI) under contract number 22.00094, and from Wings Health in the context of a proof-of-concept study. He received royalties from Springer, and an honorarium from Lundbeck for speaking at a symposium. He is a co-founder, member of the board and shareholder of Therayou AG, active in digital and blended mental healthcare. He is compensated for providing psychotherapy to patients, acting as a supervisor, serving as a self-experience facilitator (‘Selbsterfahrungsleiter’), and for postgraduate training of psychotherapists, psychosomatic specialist, and supervisors. FV received funding from German Cancer Aid, Deutsche Kinderkrebsstiftung/ Deutsche Leukämie-Forschungs-Hilfe and Innovationsfonds for studies including coaching, communication and communication trainings. He received royalties for book chapters regarding communication. He is a member of EAPM and has founded the special interest group (sig) transplantation medicine of the EAPM. He is one of the spokesmen of this sig. He is spokesman of the Dt. Kollegium für Psychosomatische Medizin (DKPM) and the Dt. Gesellschaft für Psychosomatische Medizin und Ärztliche Psychotherapie (DGPM) for Consultation and Liaison Psychosomatics; of the Dt. Kollegium für Psychosomatische Medizin (DKPM) and the Dt. Gesellschaft für Psychosomatische Medizin und Ärztliche Psychotherapie (DGPM) for transplantation medicine, and of the working group for communication of the psychooncology work group (PSO) of German Cancer Society (DKG). He is compensated for acting as a trainer for postgraduate training of communication trainings. CF received funding from the Austrian Science Fund for project KLI 1100. He is current president of the Austrian Society of Psychosomatics and Psychotherapeutic Medicine (ÖGPPM). He is compensated for acting as a trainer for communication in healthcare and for postgraduate training of psychosomatic medicine and as a supervisor. RS received funding from the Stanley Thomas Johnson Stiftung & Gottfried und Julia Bangerter-Rhyner-Stiftung under project no. PC 05/18, from Gesundheitsförderung Schweiz under project no. 18.191/K50001, from the Swiss Heart Foundation under project no. FF21101, in the context of a Horizon Europe project from the Swiss State Secretariat for Education, Research and lnnovation (SERI) under contract number 22.00094, and from Wings Health in the context of a proof-of-concept study. He received royalties from the publishing houses Kohlhammer and Springer. He received an honorarium from Novartis for speaking at a symposium. He is member of the scientific advisory Board of the Swiss Academy of Psychosomatic and Psychosocial Medicine. He is spokesman of the Dt. Kollegium für Psychosomatische Medizin (DKPM) and the Dt. Gesellschaft für Psychosomatische Medizin und Ärztliche Psychotherapie (DGPM) for Consultation and Liaison Psychosomatics. He is founder and managing director of the “Psychosomatic and Psychosocial Services GmbH”, active in psychosomatic and psychosocial training and further education and member of the Board of Trustees of the Foundation for Psychosomatics and Social Medicine (Ascona Foundation). He is compensated for acting as a trainer for postgraduate training of psychosomatic medicine and as a supervisor. The other authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

The study aimed to determine whether specific integrative group psychotherapy (IGPT), based on CBT, combined with techniques of psychodynamic therapy and mindful body and emotional awareness is more effective than non-specific supportive group psychotherapy (SGPT) and treatment as usual (TAU) alone. A total of 120 SSD patients were randomly assigned to IGPT, SGPT or TAU groups. Both IGPT and SGPT showed significantly lower SSD-12 scores at the 4, 8, and 12-week follow-ups compared to TAU. No significant differences were observed between IGPT and SGPT at any follow-up point. These findings highlight the potential benefits of group psychotherapy in SSD treatment., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Communicating bad news such as a new cancer diagnosis to patients may have a major impact on their well-being. We investigated differences in patients' psychological distress due to the disclosure of bad news by telephone compared to in person in a systematic review and meta-analysis., Methods: We included all studies that investigated anxiety, depressive or post-traumatic stress disorder (PTSD) symptoms in adult patients in whom bad news by telephone compared to in person were disclosed. We systematically searched PubMed, Embase, PsycINFO and CINAHL from the inception of each database to October 18, 2022. We included randomized and non-randomized trials., Results: We screened 5944 studies and included 11 studies in the qualitative analysis and 9 in the meta-analyses, including four randomized controlled trials. Overall, the quality of studies was moderate to good. There was no difference regarding psychological distress when bad news was disclosed by telephone compared to in person with similar symptom levels of anxiety (3 studies, 285 participants; standardized mean difference [SMD] 0.10 [95% CI -0.15 to 0.35]), depression (3 studies, 284 participants; SMD 0.10 [95% CI -0.30 to 0.49]), and PTSD (2 studies, 171 participants; SMD -0.01 [95% CI -0.48 to 0.36]). Results were similar for satisfaction with care., Discussion: This meta-analysis found no difference regarding psychological distress regardless if bad news were disclosed by telephone or in person, but there were overall only few and heterogeneous studies with a small number of eligible patients. The findings suggest that the modality of disclosure might play a secondary role and the way in which the bad news are communicated might be more important., (© 2023. The Author(s).)

Background: Cancer is related to not only physical but also mental suffering. Notably, body image disturbances are highly relevant to cancer-related changes often persisting beyond recovery from cancer. Scalable and low-barrier interventions that can be blended with face-to-face psychotherapy for cancer survivors are highly warranted., Objective: The aim of the study is to investigate whether smartphone-based bodily interventions are more effective to improve the mood of patients with cancer than smartphone-based fairy tale interventions (control intervention)., Methods: We recruited patients with cancer in 2 Swiss hospitals and conducted daily, fully automated smartphone-based interventions 6 times a week for 5 consecutive weeks, blended with weekly face-to-face group body psychotherapy. We applied 2 types of smartphone-based interventions using a within-subject design, randomly assigning patients daily to either bodily interventions or fairy tales. Each intervention type was presented 3 times a week. For this secondary analysis, 3-level mixed models were estimated with mood assessed by the 3 Multidimensional Mood Questionnaire subscales for good-bad mood, wakefulness, and calmness as key indicators. In addition, the effects on experience of presence, vitality, and burden assessed with visual analog scales were investigated., Results: Based on the data from s=732 interventions performed by 36 participants, good-bad mood improved (β=.27; 95% CI 0.062-0.483), and participants became calmer (β=.98; 95% CI 0.740-1.211) following smartphone-based interventions. Wakefulness did not significantly change from pre- to postsmartphone-based intervention (β=.17; 95% CI -0.081 to 0.412). This was true for both intervention types. There was no interaction effect of intervention type with change in good-bad mood (β=-.01; 95% CI -0.439 to 0.417), calmness (β=.22; 95% CI -0.228 to 0.728), or wakefulness (β=.14; 95% CI -0.354 to 0.644). Experience of presence (β=.34; 95% CI 0.271-0.417) and vitality (β=.35; 95% CI 0.268-0.426) increased from pre- to postsmartphone-based intervention, while experience of burden decreased (β=-0.40; 95% CI -0.481 to 0.311). Again, these effects were present for both intervention types. There were no significant interaction effects of intervention type with pre- to postintervention changes in experience of presence (β=.14; 95% CI -0.104 to 0.384), experience of vitality (β=.06; 95% CI -0.152 to 0.265), and experience of burden (β=-.16; 95% CI -0.358 to 0.017)., Conclusions: Our results suggest that both smartphone-based audio-guided bodily interventions and fairy tales have the potential to improve the mood of cancer survivors., Trial Registration: ClinicalTrials.gov NCT03707548; https://clinicaltrials.gov/study/NCT03707548., International Registered Report Identifier (irrid): RR2-10.1186/s40359-019-0357-1., (©Gunther Meinlschmidt, Astrid Grossert, Cornelia Meffert, Noa Roemmel, Viviane Hess, Christoph Rochlitz, Miklos Pless, Sabina Hunziker, Brigitta Wössmer, Ulfried Geuter, Rainer Schaefert. Originally published in JMIR Cancer (https://cancer.jmir.org), 28.08.2023.)

Background: Stepped and Collaborative Care Models (SCCMs) have shown potential for improving mental health care. Most SCCMs have been used in primary care settings. At the core of such models are initial psychosocial distress assessments commonly in form of patient screening. We aimed to assess the feasibility of such assessments in a general hospital setting in Switzerland., Methods: We conducted and analyzed eighteen semi-structured interviews with nurses and physicians involved in a recent introduction of a SCCM model in a hospital setting, as part of the SomPsyNet project in Basel-Stadt. Following an implementation research approach, we used the Tailored Implementation for Chronic Diseases (TICD) framework for analysis. The TICD distinguishes seven domains: guideline factors, individual healthcare professional factors, patient factors, professional interactions, incentives and resources, capacity for organizational change, and social, political, and legal factors. Domains were split into themes and subthemes, which were used for line-by-line coding., Results: Nurses and physicians reported factors belonging to all seven TICD domains. An appropriate integration of the psychosocial distress assessment into preexisting hospital processes and information technology systems was the most important facilitator. Subjectivity of the assessment, lack of awareness about the assessment, and time constraints, particularly among physicians, were factors undermining and limiting the implementation of the psychosocial distress assessment., Conclusions: Awareness raising through regular training of new employees, feedback on performance and patient benefits, and working with champions and opinion leaders can likely support a successful implementation of routine psychosocial distress assessments. Additionally, aligning psychosocial distress assessments with workflows is essential to assure the sustainability of the procedure in a working context with commonly limited time., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Aebi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The COVID-19 pandemic posed new challenges for integrated health care worldwide. Our study aimed to describe newly implemented structures and procedures of psychosocial consultation and liaison (CL) services in Europe and beyond, and to highlight emerging needs for co-operation., Methods: Cross-sectional online survey from June to October 2021, using a self-developed 25-item questionnaire in four language versions (English, French, Italian, German). Dissemination was via national professional societies, working groups, and heads of CL services., Results: Of the participating 259 CL services from Europe, Iran, and parts of Canada, 222 reported COVID-19 related psychosocial care (COVID-psyCare) in their hospital. Among these, 86.5% indicated that specific COVID-psyCare co-operation structures had been established. 50.8% provided specific COVID-psyCare for patients, 38.2% for relatives, and 77.0% for staff. Over half of the time resources were invested for patients. About a quarter of the time was used for staff, and these interventions, typically associated with the liaison function of CL services, were reported as most useful. Concerning emerging needs, 58.1% of the CL services providing COVID-psyCare expressed wishes for mutual information exchange and support, and 64.0% suggested specific changes or improvements that they considered essential for the future., Conclusion: Over 80% of participating CL services established specific structures to provide COVID-psyCare for patients, their relatives, or staff. Mostly, resources were committed to patient care and specific interventions were largely implemented for staff support. Future development of COVID-psyCare warrants intensified intra- and inter-institutional exchange and co-operation., Competing Interests: Declaration of Competing Interest All other authors declare that they have no competing financial interests related to this study., (Copyright © 2023. Published by Elsevier Inc.)

Background: Patients may prefer different levels of involvement in decision-making regarding their medical care which may influence their medical knowledge., Objective: We investigated associations of patients' decisional control preference (DCP) with their medical knowledge, ward round performance measures (e.g., duration, occurrence of sensitive topics), and perceived quality of care measures (e.g., trust in the healthcare team, satisfaction with hospital stay)., Design: This is a secondary analysis of a randomized controlled multicenter trial conducted between 2017 and 2019 at 3 Swiss teaching hospitals., Participants: Adult patients that were hospitalized for inpatient care., Main Measures: The primary outcome was patients' subjective average knowledge of their medical care (rated on a visual analog scale from 0 to 100). We classified patients as active, collaborative, and passive according to the Control Preference Scale. Data collection was performed before, during, and after the ward round., Key Results: Among the 761 included patients, those with a passive DCP had a similar subjective average (mean ± SD) knowledge (81.3 ± 19.4 points) compared to patients with a collaborative DCP (78.7 ± 20.3 points) and active DCP (81.3 ± 21.5 points), p = 0.25. Regarding patients' trust in physicians and nurses, we found that patients with an active vs. passive DCP reported significantly less trust in physicians (adjusted difference, - 5.08 [95% CI, - 8.69 to - 1.48 points], p = 0.006) and in nurses (adjusted difference, - 3.41 [95% CI, - 6.51 to - 0.31 points], p = 0.031). Also, patients with an active vs. passive DCP were significantly less satisfied with their hospital stay (adjusted difference, - 7.17 [95% CI, - 11.01 to - 3.34 points], p < 0.001)., Conclusion: Patients with active DCP have lower trust in the healthcare team and lower overall satisfaction despite similar perceived medical knowledge. The knowledge of a patient's DCP may help to individualize patient-centered care. A personalized approach may improve the patient-physician relationship and increase patients' satisfaction with medical care., Trial Registration: ClinicalTrials.gov (NCT03210987)., (© 2022. The Author(s).)

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT 3 receptor family. 5-HT 3 Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT 3 R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D., (© 2022. The Author(s).)

Introduction: Intensive care unit patients are at risk for post-intensive care syndrome (PICS), which includes psychological, physical and/or cognitive sequelae after their hospital stay. Our aim was to investigate PICS in adult patients with out-of-hospital cardiac arrest (OHCA)., Methods: In this prospective observational cohort study, we assessed risks for PICS at 3 and 12-month follow-up within the following domains: a) physical impairment (EuroQol [EQ-5D-3L]), b) cognitive functioning (Cerebral Performance Category [CPC] score >1, modified Rankin Scale [mRS] >2) and c) psychological burden (Hospital Anxiety and Depression Scale [HADS], Impact of Event Scale-Revised [IES-R])., Results: At 3 months, 69/139 patients (50%) met the definition of PICS including 37% in the physical domain, 25% in the cognitive domain and 13% in the psychological domain. Intubation (OR 2.3, 95%CI 1.1 to 5,0 p = 0.03), sedatives (OR 3.4, 95%CI 1 to 11, p = 0.045), mRS at discharge (OR 4.3, 95%CI 1.70 to 11.01, p = 0.002), CPC at discharge (OR 3.3, 95%CI 1.4 to 7.6, p = 0.005) and post-discharge work loss (OR 13.4, 95%CI 1.7 to 107.5, p = 0.014) were significantly associated with PICS. At 12 months, 52/110 (47%) patients had PICS, which was associated with prolonged duration of rehabilitation, higher APACHE scores, and higher mRS and CPC scores at hospital discharge., Conclusions: Nearly half of long-term OHCA survivors show PICS after 3 and 12 months. These high numbers call for more emphasis on appropriate screening and treatment in this patient population. Future studies should evaluate whether early identification of these patients enables preventive strategies and treatment options., Competing Interests: The authors have declared that no competing interests exist.

Background: The coronavirus disease 2019 (COVID-19) pandemic was accompanied by new challenges for psychosocial health care to enable the support of affected patients, their families, and staff in general hospitals. In this study, we aimed to describe the structures and procedures put in place by psychosomatic, psychiatric, and psychological consultation and liaison (CL) services in German, Austrian, and Swiss general hospitals, and to elucidate the emerging needs for cooperation, networking, and improvement., Methods: We conducted a cross-sectional online survey between December 2020 and May 2021, using a 25-item questionnaire derived from relevant literature, professional experience, and consultation with the participating professional societies. The survey was disseminated via national professional societies, relevant working and interest groups, and heads of the above-mentioned CL services., Results: We included responses from 98 CL services in the analyses, with a total response rate of 55% of surveyed hospital CL services; 52 responses originated from Germany, 20 from Austria, and 26 from Switzerland. A total of 77 (79%) of the 98 responding CL services reported that "COVID-19-related psychosocial care" (COVID-psyCare) was provided in their hospital. Among these, 47 CL services (61%) indicated that specific cooperation structures for COVID-psyCare had been established within the hospital. A total of 26 CL services (34%) reported providing specific COVID-psyCare for patients, 19 (25%) for relatives, and 46 (60%) for staff, with 61, 12, and 27% of time resources invested for these target groups, respectively. Regarding emerging needs, 37 (48%) CL services expressed wishes for mutual exchange and support regarding COVID-psyCare, and 39 (51%) suggested future changes or improvements that they considered essential., Conclusion: More than three-quarters of the participating CL services provided COVID-psyCare for patients, their relatives, or staff. The high prevalence of COVID-psyCare services targeting hospital staff emphasizes the liaison function of CL services and indicates the increased psychosocial strain on health care personnel during the COVID-19 pandemic. Future development of COVID-psyCare warrants intensified intra- and interinstitutional exchange and support., Trial Registration: ClinicalTrials.gov NCT04753242, version 11 February 2021., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schaefert, Stein, Meinlschmidt, Roemmel, Huber, Hepp, Saillant, Fazekas and Vitinius.)

Background: Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit ( HTR3 ) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS)., Aim: To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS., Methods: In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays., Results: Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model ( F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score ( F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT 3 AC variant receptors., Conclusion: We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS., Competing Interests: Conflict-of-interest statement: APC Microbiome Ireland has conducted studies in collaboration with several companies, including GSK, Pfizer, Cremo, Suntory, Wyeth, Mead Johnson, Nutricia, 4D Pharma, and DuPont. Dinan TG has been an invited speaker at meetings organized by Servier, Lundbeck, Janssen, and AstraZeneca and has received research funding from Mead Johnson, Cremo, Suntory Wellness, Nutricia, and 4D Pharma. Clarke G has been an invited speaker at meetings organized by Janssen and is receipt of research funding from Pharmavite. The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)