Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study

BACKGROUND: Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit ( AIM: To assess the association of 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 - RESULTS: Depressive and anxiety symptoms significantly worsened with increasing numbers of minor CONCLUSION: We have provided the first evidence tha

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome

5-HT; IBS; Transportador de serotonina5-HT; IBS; Transportador de serotonina5-HT; IBS; Serotonin transporterIrritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis

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

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).

A vignette study of option refusal and decision deferral as two forms of decision avoidance: Situational and personal predictors.

The avoidance of a decision is a phenomenon that has been studied in various forms and psychological disciplines. Nevertheless, previous studies often lacked the integration of situational as well as personal factors in predicting decision avoidance. Additionally, studies about conditions that affect different forms of decision avoidance are still lacking. Therefore, this study investigated how situational and personal factors influenced two different forms of decision avoidance: 1) the option of deferring choice to a later point in time (decision deferral) and 2) the option to refuse both alternatives (option refusal). Furthermore, this study aimed to analyze how the participants experienced their avoidance behavior. This served the purpose of capturing functional and dysfunctional avoidance out of a subjective perspective instead of providing predefined best options. A vignette study based on realistic decision-making scenarios within a student's daily life was conducted. In an online survey, N = 312 participants chose to decide, to defer choice, or to refuse options in the context of eight vignettes. Situational factors (time pressure, lack of information, and attractiveness of alternatives) were systematically varied. Additionally, the following personal factors were captured by questionnaires: indecisiveness, decision-making styles, and the need for cognitive closure. Further factors were captured, but not systematically varied: selection difficulty, importance of a decision, and similarity of alternatives. The individual satisfaction with decision-making behavior was evaluated as an indicator of subjective decision quality. The results showed that decision deferral was affected by situational factors (primarily due to time pressure), selection difficulty, and individual indecisiveness. The refusal of current alternatives was exclusively influenced by situational factors, mainly the manipulated attractiveness of the choice-set. The results emphasize the functionality of refusing unattractive options and help to distinguish adaptive and maladaptive coping forms in decision-making

Pain and psyche in a patient with irritable bowel syndrome: chicken or egg? A time series case report

Background!#!Irritable bowel syndrome (IBS) appears to have a bidirectional interaction with both depressive and anxiety-related complaints. However, it remains unclear how exactly the psychological complaints, at the individual level, are related to somatic symptoms on a daily basis. This single case study investigates how somatic and psychological variables are temporally related in a patient with irritable bowel syndrome.!##!Case report!#!The patient was a woman in her mid-twenties with an IBS diagnosis. She reported frequent soft bowel movements (5-6 times per day), as well as flatulence and abdominal pain. She resembled a typical IBS patient; however, a marked feature of the patient was her high motivation for psychosomatic treatment as well as her willingness to try new strategies regarding the management of her symptoms. As an innovative approach this single case study used a longitudinal, observational, time series design. The patient answered questions regarding somatic and psychological variables daily over a period of twelve weeks with an online diary. The diary data was analysed using an autoregressive (VAR) modeling approach. Time series analyses showed that in most variables, strong same-day correlations between somatic (abdominal pain, daily impairment) and psychological time series (including coping strategies) were present. The day-lagged relationships indicated that higher values in abdominal pain on one day were predictive of higher values in the psychological variables on the following day (e.g. nervousness, tension, catastrophizing, hopelessness). The use of positive thinking as a coping strategy was helpful in reducing the pain on the following days.!##!Conclusion!#!In the presented case we found a high correlation between variables, with somatic symptoms temporally preceding psychological variables. In addition, for this patient, the use of positive thoughts as a coping strategy was helpful in reducing pain

Different Dimensions of Affective Processing in Patients With Irritable Bowel Syndrome: A Multi-Center Cross-Sectional Study

Objective: Deficits in affective processing are associated with impairments in both mental and physical health. The role of affective processing in patients with functional somatic complaints such as irritable bowel syndrome (IBS) remains unclear. Most studies have focused on the capacity for emotional awareness and expression, but neglect other dimensions of affective processing. Therefore, this study aimed to systematically analyze differences in six different dimensions of affective processing between patients with IBS and healthy controls (HCs). Additionally, we exploratively investigated the impact of IBS symptom severity, psychological distress, and attachment styles on affective processing in IBS. Methods: A controlled cross-sectional multi-center study was conducted. Overall, 127 patients with IBS were compared with 127 matched HCs using multivariate analysis of variances. Affective processing was operationalized in line with the affect cascade model on six specific dimensions: emotional experience, emotional awareness, affect tolerance, affect differentiation, affect regulation, and emotional communication. They were measured using two subscales of the Mentalizing Questionnaire (MZQ) and four subscales of the Operationalized Psychodynamic Diagnosis-Structure Questionnaire (OPD-SQ). Linear regression analysis was used to investigate the influence of IBS symptom severity (IBS-Severity Scoring System, IBS-SSS), depression (Patient Health Questionnaire, PHQ-9), anxiety (General Anxiety Disorder, GAD-7), and anxious and avoidant attachment styles (Experiences in Close Relationships Scale, ECR-RD12) on the different dimensions of affective processing in IBS. Results: Patients with IBS compared to HCs showed deficits in all six dimensions of affective processing. Deficits were largest for affect tolerance (d = 0.849) and lowest for emotional experience (d = 0.222) and emotional awareness (d = 0.420). Moderate effect sizes were found for affect differentiation (d = 0.773), emotional communication (d = 0.665), and affect regulation (d = 0.552). Moreover, explorative analyses indicated that affective processing in patients with IBS was significantly influenced by levels of anxiety and insecure attachment. Conclusion: The results indicate a specific pattern of affective processing abilities in patients with IBS. The deficits in affective processing are more prominent in the area of understanding and tolerating difficult affective states than experiencing affective states. This opens interesting perspectives for the development of specific psychotherapeutic interventions

The Validity of Somatic Symptom Disorder in Patients With Gastrointestinal Complaints

Background and Goal: The current diagnostic concept of somatic symptom disorder (SSD) aims to capture psychological burden due to bodily complaints independent of the medical cause. The aim of this study was to compare patients with chronic gastrointestinal (GI) complaints with SSD (SSD+) and without SSD (SSD-) along sociodemographic, clinical, and psychological characteristics. Study: This cross-sectional study included 199 patients (n=92 SSD+ and n=107 SSD-) with distressing and chronic abdominal/lower GI complaints (>= 6 mo) recruited from several primary, secondary, and tertiary medical care units. SSD+ patients were separated from SSD- patients by psychobehavioral positive criteria. Psychological distress (somatization, depression, anxiety, and illness anxiety) and risk factors (adverse childhood experiences, insecure attachment, mentalizing capacity, and levels of personality functioning) were measured. Nonparametric group comparisons were performed to analyze the differences of sociodemographic, clinical, and psychological characteristics between SSD+ and SSD- patients. Results: About half of the SSD+ patients had a functional GI disorder and a third had an inflammatory bowel disease. SSD+ patients reported higher GI pain severity, higher health-related and work-related impairment, and higher psychological distress, especially illness anxiety, as well as higher mentalizing and personality functioning deficits. Conclusions: Overall, psychobehavioral positive criteria of SSD seem to be a valid identifier of patients exhibiting a high psychological burden, independent of the medical explanation of the GI complaints. There is a substantial overlap of SSD and general mental burden, but also evidence for a specific disease entity