Psychophysiology of Irritable Bowel Syndrome

肠易激综合症的心理生理学

• 批准号: 7901982
• 负责人: WILLIAM E WHITEHEAD
• 金额: $ 9.13万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901982
• 关键词: Accounting; Address; Adult; Affect; Attention; Bacteria; Bacterial Gastroenteritis; Biological; Biopsy; Boxing; Childhood; Classification; Clinical; Cluster Analysis; Collaborations; Collection; Consensus; Constipation; Data; Databases; Development; Diagnosis; Diarrhea; Diet; Differential Diagnosis; Dimensions; Disease; Distress; Effectiveness; Environment; Environmental Exposure; Equation; Etiology; Failure; Feces; Fiber; Functional disorder; Future; Gastroenterologist; Gastrointestinal Motility; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Research; Genotype; Glean; Goals; Grant; Health; Health Care Costs; Heterogeneity; Impairment; Inflammation; Inflammatory; Interdisciplinary Study; Irritable Bowel Syndrome; Label; Learning; Life; Literature; Logistic Regressions; MAP2K1 gene; Measures; Methodology; Modeling; Outcome; Pain; Parents; Patients; Perception; Phenotype; Physiological; Pilot Projects; Population; Principal Component Analysis; Probiotics; Prospective Studies; Protocols documentation; Psychological reinforcement; Psychologist; Psychophysiology; Quality of life; Recording of previous events; Recruitment Activity; Regression Analysis; Reporting; Research; Research Personnel; Review Literature; Risk Factors; Rome; Serum; Sick Role; Single Nucleotide Polymorphism; Small Intestines; Specimen; Subgroup; Surveys; Symptoms; Temporomandibular Joint Disorders; Testing; Theoretical model; Woman; Work; base; case control; cell motility; chronic pain; cohort; drug development; effective therapy; experience; gene environment interaction; gene interaction; genetic association; genetic risk factor; improved; psychologic; psychological distress; psychosocial; public health relevance; social; stability testing; systematic review; three-dimensional modeling; translational study

DESCRIPTION (provided by applicant): Irritable bowel syndrome (IBS) affects 10% of US adults and is associated with significant impairment in quality of life. Despite decades of research, there is no consensus on its pathophysiology and no consistently effective treatment. Genetic studies have yielded inconsistent findings. Our hypothesis is that this has occurred because IBS is not a unitary disorder but a group of different disorders with distinct etiologies, which require different treatments. Our previous grant supported this heterogeneity hypothesis: we tested more than 50 physiological and psychological variables in 267 IBS patients and identified 4 independent clusters: constipation- predominant (IBS-C), diarrhea-predominant (IBS-D), pain-hypersensitive (IBS-Pn), and psychologically distressed (IBS-Psy). The aims of this proposal are to (1) identify genetic polymorphisms associated with these 4 IBS phenotypes; (2) develop, for each phenotype, an etiologic model that includes gene-environment and gene-gene interactions; and (3) test and refine these models using structural equation modeling. Associations between each IBS phenotype and genetic polymorphisms will be assessed using a Pain Panel consisting of 350 selected genes (3200 SNPs) gleaned from a systematic literature review. Associations will be considered significant only if confirmed in two independent cohorts of 225-300 IBS patients and 200-225 healthy controls. As an example of the types of models we will construct, we hypothesize for the IBS-Pn phenotype, genes regulating inflammation (e.g. MAP2K1) and genes regulating pain sensitivity more directly (e.g., GABRG2) interact to influence vulnerability to IBS-Pn, and we hypothesize that inflammatory genes may require the environmental trigger of bacterial gastroenteritis for expression while genes related to pain sensitivity may be modulated by childhood social learning through modeling and reinforcement of illness behavior. We will also test the stability of IBS phenotypes by (1) retesting 50 IBS patients with the full phenotyping protocol 6 months after initial testing and (2) surveying all subjects annually to discover changes in symptoms and diagnoses. Data acquired in this study will augment our database of IBS patients and healthy controls, which contains biological specimens (DNA, serum, some biopsies) as well as clinical and physiological data stored for future studies. This translational study entails multidisciplinary collaboration between experienced teams of pain geneticists, gastroenterologists, and psychologists. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE The irritable bowel syndrome (IBS) affects 10% of the population and results in $8 billion dollars in annual health care costs, but there is no consensus on its pathophysiology or treatment. The hypothesis of our research is that IBS is not one disorder but a group of disorders with different etiologies, for which different treatments will be appropriate. Identifying these different phenotypes of IBS and the genetic markers associated with them may help to identify new targets for drug development and may help us to individualize treatment and thereby make it more successful.