We provide a general framework for understanding functional gastrointestinal disorders (FGIDs) from a biopsychosocial perspective. More specifically, we provide an overview of the recent research on ...how the complex interactions of environmental, psychological, and biological factors contribute to the development and maintenance of FGIDs. We emphasize that considering and addressing all these factors is a conditio sine qua non for appropriate treatment of these conditions. First, we provide an overview of what is currently known about how each of these factors—the environment, including the influence of those in an individual’s family, the individual’s own psychological states and traits, and the individual’s (neuro)physiological make-up—interact to ultimately result in the generation of FGID symptoms. Second, we provide an overview of commonly used assessment tools that can assist clinicians in obtaining a more comprehensive assessment of these factors in their patients. Finally, the broader perspective outlined earlier is applied to provide an overview of centrally acting treatment strategies, both psychological and pharmacological, which have been shown to be efficacious to treat FGIDs.
Although it has long been hypothesized that attachment figures provide individuals with a sense of safety and security, the neural mechanisms underlying attachment-induced safety have not been ...explored. Here, we investigated whether an attachment figure acts as a safety signal by exploring whether viewing an attachment figure during a threatening experience (physical pain) led to increased activity in a neural region associated with safety signaling, the ventromedial prefrontal cortex (VMPFC), and corresponding reductions in pain. Female participants in long-term romantic relationships were scanned as they received painful stimuli while viewing pictures of their partner and control images (stranger, object). Consistent with the idea that the attachment figure may signal safety, results revealed that viewing partner pictures while receiving painful stimulation led to reductions in self-reported pain ratings, reductions in pain-related neural activity (dorsal anterior cingulate cortex, anterior insula), and increased activity in the VMPFC. Moreover, greater VMPFC activity in response to partner pictures was associated with longer relationship lengths and greater perceived partner support, further highlighting a role for the VMPFC in responding to the safety value of the partner. Last, greater VMPFC activity while viewing partner pictures was associated with reduced pain ratings and reduced pain-related neural activity. An implication of these findings is that, in the same way that stimuli that historically have threatened survival (e.g., snakes, spiders) are considered to be prepared fear stimuli, attachment figures, who have historically benefited survival, may serve as prepared safety stimuli, reducing threat- or distress-related responding in their presence.
Background & Aims Although childhood and adult abuse are more prevalent among patients with irritable bowel syndrome (IBS) than healthy individuals (controls), other types of early adverse life ...events (EALs) have not been well characterized. We investigated whether different types of EALs, before age 18 years, are more prevalent among patients with IBS, and the effects of sex and nongastrointestinal symptoms on the relationship between EALs and IBS. Methods EALs were evaluated in 294 IBS patients (79% women) and 435 controls (77% women) using the Early Trauma Inventory Self-Report Form, which delineates subcategories of general trauma and physical, emotional, and sexual abuse. Validated questionnaires assessed gastrointestinal, psychological, and somatic symptoms. Results Compared with controls, IBS patients reported a higher prevalence of general trauma (78.5% vs 62.3%), physical punishment (60.6% vs 49.2%), emotional abuse (54.9% vs 27.0%), and sexual events (31.2% vs 17.9%) (all P < .001). These significant differences were observed mainly in women. Of the EAL domains, emotional abuse was the strongest predictor of IBS ( P < .001). Eight of the 27 EAL items were significant ( P < .001) and increased the odds of having IBS by 108% to 305%. Although EALs and psychological variables were related, EALs had an independent association with IBS ( P = .04). Conclusions Various types of EALs are associated with the development of IBS—particularly among women. Psychological distress and somatic symptoms might contribute to this relationship. When appropriate, EALs and nongastrointestinal symptoms should be assessed in IBS patients.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is thought to involve alterations in the gut microbiome, but robust microbial signatures have been challenging to identify. ...As prior studies have primarily focused on composition, we hypothesized that multi-omics assessment of microbial function incorporating both metatranscriptomics and metabolomics would further delineate microbial profiles of IBS and its subtypes.
Fecal samples were collected from a racially/ethnically diverse cohort of 495 subjects, including 318 IBS patients and 177 healthy controls, for analysis by 16S rRNA gene sequencing (n = 486), metatranscriptomics (n = 327), and untargeted metabolomics (n = 368). Differentially abundant microbes, predicted genes, transcripts, and metabolites in IBS were identified by multivariate models incorporating age, sex, race/ethnicity, BMI, diet, and HAD-Anxiety. Inter-omic functional relationships were assessed by transcript/gene ratios and microbial metabolic modeling. Differential features were used to construct random forests classifiers.
IBS was associated with global alterations in microbiome composition by 16S rRNA sequencing and metatranscriptomics, and in microbiome function by predicted metagenomics, metatranscriptomics, and metabolomics. After adjusting for age, sex, race/ethnicity, BMI, diet, and anxiety, IBS was associated with differential abundance of bacterial taxa such as Bacteroides dorei; metabolites including increased tyramine and decreased gentisate and hydrocinnamate; and transcripts related to fructooligosaccharide and polyol utilization. IBS further showed transcriptional upregulation of enzymes involved in fructose and glucan metabolism as well as the succinate pathway of carbohydrate fermentation. A multi-omics classifier for IBS had significantly higher accuracy (AUC 0.82) than classifiers using individual datasets. Diarrhea-predominant IBS (IBS-D) demonstrated shifts in the metatranscriptome and metabolome including increased bile acids, polyamines, succinate pathway intermediates (malate, fumarate), and transcripts involved in fructose, mannose, and polyol metabolism compared to constipation-predominant IBS (IBS-C). A classifier incorporating metabolites and gene-normalized transcripts differentiated IBS-D from IBS-C with high accuracy (AUC 0.86).
IBS is characterized by a multi-omics microbial signature indicating increased capacity to utilize fermentable carbohydrates-consistent with the clinical benefit of diets restricting this energy source-that also includes multiple previously unrecognized metabolites and metabolic pathways. These findings support the need for integrative assessment of microbial function to investigate the microbiome in IBS and identify novel microbiome-related therapeutic targets. Video Abstract.
Chronic overlapping pain conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This "centralized pain" phenotype has been described using a large and diverse set ...of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here, we used 3 cohorts, including patients with urologic chronic pelvic pain syndrome, a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain. Using exploratory and confirmatory factor analysis, we identified 2 general factors in all 3 cohorts, one characterized by a broad increased sensitivity to internal somatic sensations,environmental stimuli, and diffuse pain, termed Generalized Sensory Sensitivity, and one characterized by constitutional symptoms-Sleep, Pain, Affect, Cognition, Energy (SPACE). Longitudinal analyses in the urologic chronic pelvic pain syndrome cohort found the same 2-factor structure at month 6 and 1 year, suggesting that the 2-factor structure is reproducible over time. In secondary analyses, we found that Generalized Sensory Sensitivity particularly is associated with the presence of comorbid COPCs, whereas SPACE shows modest associations with measures of disability and urinary symptoms. These factors may represent an important and distinct continuum of symptoms that are indicative of the centralized pain phenotype at high levels. Future research of COPCs should accommodate the measurement of each factor.
The beneficial effects of mindful awareness and mindfulness meditation training on physical and psychological health are thought to be mediated in part through changes in underlying brain processes. ...Functional connectivity MRI (fcMRI) allows identification of functional networks in the brain. It has been used to examine state-dependent activity and is well suited for studying states such as meditation. We applied fcMRI to determine if Mindfulness-Based Stress Reduction (MBSR) training is effective in altering intrinsic connectivity networks (ICNs). Healthy women were randomly assigned to participate in an 8-week Mindfulness-Based Stress Reduction (MBSR) training course or an 8-week waiting period. After 8
weeks, fMRI data (1.5
T) was acquired while subjects rested with eyes closed, with the instruction to pay attention to the sounds of the scanner environment. Group independent component analysis was performed to investigate training-related changes in functional connectivity. Significant MBSR-related differences in functional connectivity were found mainly in auditory/salience and medial visual networks. Relative to findings in the control group, MBSR subjects showed (1) increased functional connectivity within auditory and visual networks, (2) increased functional connectivity between auditory cortex and areas associated with attentional and self-referential processes, (3) stronger anticorrelation between auditory and visual cortex, and (4) stronger anticorrelation between visual cortex and areas associated with attentional and self-referential processes. These findings suggest that 8
weeks of mindfulness meditation training alters intrinsic functional connectivity in ways that may reflect a more consistent attentional focus, enhanced sensory processing, and reflective awareness of sensory experience.
►MBSR training enhances functional connectivity within sensory networks. ►MBSR subjects show greater auditory/visual reciprocal modulation. ►MBSR training alters connectivity between attention and sensory networks.
Irritable bowel syndrome (IBS) is a chronic and debilitating medical condition with few efficacious pharmacological or psychosocial treatment options available. Evidence suggests that visceral ...anxiety may be implicated in IBS onset and severity. Thus, cognitive-behavioral treatment (CBT) that targets visceral anxiety may alleviate IBS symptoms.
The current study examined the efficacy of a CBT protocol for the treatment of IBS which directly targeted visceral sensations. Participants (N = 110) were randomized to receive 10 sessions of either: (a) CBT with interoceptive exposure (IE) to visceral sensations; (b) stress management (SM); or (c) an attention control (AC), and were assessed at baseline, mid-treatment, post-treatment, and follow-up sessions.
Consistent with hypotheses, the IE group outperformed AC on several indices of outcome, and outperformed SM in some domains. No differences were observed between SM and AC. The results suggest that IE may be a particularly efficacious treatment for IBS.
Implications for research and clinical practice are discussed.
► CBT with interoceptive exposure (IE) was investigated for the treatment of IBS. ► IE was compared to stress management (SM) and attention control (AC). ► IE outperformed AC on several indices of outcome. ► IE outperformed SM on some indices of outcome. ► Treatment for IBS targeting fear and avoidance of visceral sensation is efficacious.
Background
Irritable bowel syndrome (IBS) is a common and often debilitating chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Pharmacological treatments are ...often ineffective, leading to the development of a variety of behavioral interventions. Mindfulness‐based stress reduction (MBSR) is one such program that has shown efficacy in reducing gastrointestinal (GI) symptoms and improving quality of life (QOL). This single‐arm intervention study examines the association of clinical outcomes with changes in specific aspects of mindfulness.
Methods
Adults with IBS (53 women, 15 men) participated in an 8‐week MBSR class. Primary outcomes of GI symptom severity, quality of life, and GI‐specific anxiety, as well as specific aspects of mindfulness using the Five Factor Mindfulness Questionnaire (FFMQ), were assessed at baseline, post‐treatment, and 6‐month follow‐up.
Key Results
Gastrointestinal symptom responder rate was 71%, and there was a significant pre‐post treatment change for three of the five FFMQ scales. Regression analysis indicated that change in the Act with Awareness (P = .02) facet of mindfulness was the strongest predictor of GI symptom and QOL improvement.
Conclusions & Inferences
Mindfulness‐based stress reduction training was associated with robust improvements in GI symptoms and associated problems in participants with IBS. Although significant increases in 3 of the 5 measured facets of mindfulness were found, regression analyses suggest that increases in the ability to retain present moment focus and act with awareness may be particularly important for improving outcomes in individuals with IBS. These results may inform the refinement of mindfulness‐based protocols specifically for treatment of IBS.
MBSR led to a GI symptom responder rate of 71% and a significant pre‐post treatment change for three of five facets of mindfulness (FFMQ scales). Regression analysis indicated that change in the Act with Awareness (p = .02) facet of mindfulness was the strongest predictor of GI symptom and QOL improvement. Increases in the ability to retain present‐moment focus and act with awareness may be particularly important for improving outcomes in individuals with IBS
The Specialized Center of Research Excellence (SCORE) on sex differences at University of California, Los Angeles (UCLA) has a long track record studying bidirectional interactions between different ...organs and the brain in health and disease with a strong focus on sex as a biological variable (SABV). While the initial focus was on brain-gut interactions in irritable bowel syndrome (IBS), one of the most common disorders of gut-brain interaction, the scope of our Center's research has expanded to a range of different diseases, including inflammatory bowel disease, alcohol use disorder, obesity, urological chronic pelvic pain syndrome, and vulvodynia. This expansion of research focused on the role of brain-body and brain-gut microbiome interactions in these various disorders, aligning well with the increasing importance of multidisciplinary and interdisciplinary team science. The SCORE's Career Enhancement Core (CEC) has modeled team science as applied to SABV research, with educational and training opportunities, a mentoring program, seed grant funding, and other career development experiences that enable mentees to work across the disciplines involved in brain body research. The CEC goals are: (1) To provide seed grant funds for innovative research relevant to the overall SCORE mission and research program; (2) to recruit and foster the career development of students, trainees, and junior investigators who conduct research focused on sex differences or women's health in IBS and chronic constipation and other brain-gut disorders; (3) to facilitate and promote collaboration between the UCLA SCORE and other academic programs involved in women's health education and research; and (4) to promote the importance of SABV through community outreach using collaborative and innovative approaches. These goals focus on establishing the leading research center in sex differences in basic, translational, and clinical aspects of brain-body interactions and on providing women and underrepresented individuals with research opportunities needed to become independent investigators.
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