Dose-dependent changes in real-life affective well-being in healthy community-based individuals with mild to moderate childhood trauma exposure

Background Childhood trauma exposures (CTEs) are frequent, well-established risk factor for the development of psychopathology. However, knowledge of the effects of CTEs in healthy individuals in a real life context, which is crucial for early detection and prevention of mental disorders, is incomplete. Here, we use ecological momentary assessment (EMA) to investigate CTE load-dependent changes in daily-life affective well-being and psychosocial risk profile in n = 351 healthy, clinically asymptomatic, adults from the community with mild to moderate CTE. Findings EMA revealed significant CTE dose-dependent decreases in real-life affective valence (p = 0.007), energetic arousal (p = 0.032) and calmness (p = 0.044). Psychosocial questionnaires revealed a broad CTE-related psychosocial risk profile with dose-dependent increases in mental health risk-associated features (e.g., trait anxiety, maladaptive coping, loneliness, daily hassles; p values < 0.003) and a corresponding decrease in factors protective for mental health (e.g., life satisfaction, adaptive coping, optimism, social support; p values < 0.021). These results were not influenced by age, sex, socioeconomic status or education. Conclusions Healthy community-based adults with mild to moderate CTE exhibit dose-dependent changes in well-being manifesting in decreases in affective valence, calmness and energy in real life settings, as well as a range of established psychosocial risk features associated with mental health risk. This indicates an approach to early detection, early intervention, and prevention of CTE-associated psychiatric disorders in this at-risk population, using ecological momentary interventions (EMI) in real life, which enhance established protective factors for mental health, such as green space exposure, or social support

Elevated high sensitive C-reactive protein in fibromyalgia

IntroductionFibromyalgia syndrome (FMS) is a complex chronic pain condition characterized by widespread pain and tenderness, fatigue, and sleep disturbances. Currently, factors contributing to FMS are considered to be multifactorial, and the involvement of inflammatory processes is a question of debate.ObjectiveThe aims of this study were (1) to assess whether serum concentrations of high-sensitivity C-reactive protein (hsCRP) differ between individuals diagnosed with FMS and pain-free controls, (2) to determine whether these differences are associated with clinical symptoms, and (3) to explore whether the observed differences can be explained by specific covariates such as age, weight, and smoking status.MethodsAn ANOVA was applied to identify differences of hsCRP levels between FMS and pain-free controls and an analysis of covariance (ANCOVA) was performed to investigate the dependencies of hsCRP with respect to covariates. To assess the reliability of our findings, we also utilized a Bayesian robust estimation model to determine the level of confidence associated with our results.ResultsThe results showed that individuals with FMS had higher hsCRP levels compared to healthy controls [F(1,106) = 8.802, p &lt; 0.001] and that higher hsCRP levels were significant correlated with a higher symptom burden (r = 0. 287, p = 0.008) and more tender points (r = 0.307, p = 0.005). Further, hsCRP levels were significantly associated with weight (η2 = 0.154, p &lt; 0.001), but independent of age (η2 = 0.005, p = 0.42), smoking status (η2 = 0.002, p = 0.623), or gender (η2 = 0.0045, p = 0.437), which resulted in an insignificant group effect between FMS and controls (η2 = 0.029, p = 0.052), even after controlling for covariates.ConclusionIn conclusion, this study provides evidence that sub-inflammatory processes correlate with clinical symptoms, which can be partly attributed to differences in weight, but cannot be fully explained by them. Further research is needed to elucidate the mechanisms underlying the association between hsCRP and FMS and to explore the potential therapeutic implications of targeting hsCRP in the management of FMS

How symptoms of simple acute infections affect the SSS-8 and SSD-12 as screening instruments for somatic symptom disorder in the primary care setting

ObjectiveSomatic symptom disorder (SSD) is one of the most common reasons for consultations in primary care, in addition to simple acute infections. Questionnaire-based screening instruments to identify patients at high risk of SSD are thus of great clinical relevance. Although screening instruments are frequently used, it is currently unclear to what extent they are influenced by the concurrent presence of simple acute infections. Therefore, this study aimed to investigate how symptoms of simple acute infections affect the two established questionnaires as screening instruments for somatic symptom disorder in the primary care setting.MethodsIn our cross-sectional, multicenter design, a total of 1,000 patients in primary care practices were screened using the two most established SSD screening questionnaires, the 8-item Somatic Symptom Scale (SSS-8) and the 12-item Somatic Symptom Disorder—B Criteria Scale (SSD-12), followed by clinical assessment by the primary care physician.ResultsA total of 140 patients with a simple acute infection (acute infection group, AIG) and 219 patients with chronic somatic symptoms (somatic symptom group, SSG) were included. The patients in the SSG showed higher total SSS-8 and SSD-12 scores than the patients in the AIG; however, the SSS-8 was more susceptible to changes triggered by symptoms of a simple acute infection than the SSD-12.ConclusionThese results suggest that the SSD-12 is less susceptible to symptoms of a simple acute infection. Its total score and corresponding cutoff value provide a more specific and thus less susceptible screening tool for identifying SSD in primary care

Group eye movement desensitization and reprocessing (EMDR) in chronic pain patients

The prevalence of chronic pain is increasing, and conventional pain therapies often have limited efficacy in individuals with high levels of psychological distress and a history of trauma. In this context, the use of Eye Movement Desensitization and Reprocessing (EMDR), an evidence-based psychotherapy approach for the treatment of posttraumatic stress disorder, is becoming increasingly important. EMDR shows promising results, particularly for patients with pain and high levels of emotional distress. Although group therapy is becoming increasingly popular in pain management, EMDR has mainly been studied as an individual treatment. However, a systematic review suggests that group therapy can be an effective tool for improving mental health outcomes, especially when trauma is addressed together. Based on these findings, an outpatient EMDR group program was developed for patients with chronic pain. The program consists of a total of four treatment days with 5–5.5 h therapy sessions each day and provides patients with a supportive environment in which they can learn effective pain management strategies and interact with other patients with similar experiences. Initial pilot evaluations indicate high efficacy and adequate safety for patients with chronic pain

The serotonin receptor 3E variant is a risk factor for female IBS-D

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R 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

The serotonin receptor 3E variant is a risk factor for female IBS-D

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT receptor family. 5-HT Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT 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. [Abstract copyright: © 2022. The Author(s).

Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Funder: Kennedy Trust Rheumatology Research Prize StudentshipFunder: DFG Cluster of Excellence “Precision Medicine in Chronic In-flammation” (PMI; ID: EXC2167)Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNLFunder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421Abstract: Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS

Editorial: Pain in Early and late Life - A Call for Action

Chronic pain remains a leading cause of long-term disability (GBD 2016 Disease Injury Incidence Prevalence Collaborators, 2017), affects 20% of the world's population, imposes higher costs on the society than heart disease, cancer, and diabetes combined (GBD 2016 Disease Injury Incidence Prevalence Collaborators, 2017; Buchbinder et al., 2018), and is associated with increased mortality (Tesarz et al., 2019). Despite this global relevance, therapeutic options remain unsatisfactory to date (Williams et al., 2020). Consequently, in recent years, enormous efforts have been made to expand the knowledge about the development and maintenance of chronic pain disorders and to improve treatment options. The dramatic nature of the situation and the increasing global health burden due to chronic pain even culminated recently in a "global call for action" (Buchbinder et al., 2018)