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Guadagnoli L, Abber S, Geeraerts A, Geysen H, Pauwels A, Tack J, Van Oudenhove L, Vanuytsel T. Physiological and Psychological Factors Contribute to Real-Time Esophageal Symptom Reporting in Patients With Refractory Reflux. Am J Gastroenterol 2025; 120:344-352. [PMID: 39162699 DOI: 10.14309/ajg.0000000000003033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 07/11/2024] [Indexed: 08/21/2024]
Abstract
INTRODUCTION Real-time symptom reporting during ambulatory reflux monitoring plays a key role in the evaluation of esophageal symptoms, although the underlying processes are poorly understood. We aim to identify the psychological and physiological factors associated with real-time reflux symptom reporting and symptom-reflux association parameters. METHODS Adult patients with refractory reflux symptoms completed psychosocial questionnaires and standard 24-hour pH-impedance monitoring. A hurdle-Poisson model evaluated the association between psychological and physiological (proton pump inhibitor [PPI] use, total number of reflux episodes) variables on real-time symptom frequency, assessed through a button press within 2 minutes of experiencing a symptom. Logistic regression assessed the variables associated with symptom association probability (SAP) and symptom index classification (positive/negative). Complementary machine learning analyses with 8-fold cross-validation further identified variables associated with symptom frequency and sought to optimize SAP classification performance. RESULTS Both psychological (pain-related anxiety, depressive symptoms, trait anxiety) and physiological (total number of reflux episodes, off PPI during testing) variables were associated with symptom frequency. The total number of reflux episodes and being studied off PPI were significantly associated with a higher likelihood of being classified as SAP or symptom index positive. The best-performing model in the machine learning analysis demonstrated a poor job of correctly classifying patients as SAP positive/negative (misclassification rate = 41.4%). DISCUSSION Real-time reflux symptom reporting is a multifactorial process, with both psychological and physiological processes contributing to different aspects of the reflux disease experience. Findings build on questionnaire-based research to underscore the importance of including psychological processes in our understanding of esophageal symptom reporting.
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Affiliation(s)
- Livia Guadagnoli
- Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Sophie Abber
- Department of Psychology, Florida State University, Tallahassee, Florida, USA
| | - Annelies Geeraerts
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Hannelore Geysen
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Ans Pauwels
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
- Gastroenterology Division, University Hospitals Leuven, Leuven, Belgium
| | - Lukas Van Oudenhove
- Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
- Consultation-Liaison Psychiatry, University Psychiatric Centre KU Leuven Campus Gasthuisberg, Leuven, Belgium
- Cognitive & Affective Neuroscience Lab, Department of Psychological & Brain Sciences, Dartmouth College, Hanover, New Hampshire, USA
- Leuven Brain Institute, KU Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
- Gastroenterology Division, University Hospitals Leuven, Leuven, Belgium
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Wang J, Meng N, Chen K, Huang X, Feng L, Yang C, Li Z, Sun X. The Relationship Between Depressive Symptoms and Functional Gastrointestinal Disorders (FGIDs): The Chain Mediating Effect of Sleep Disorders and Somatic Symptom. Depress Anxiety 2024; 2024:5586123. [PMID: 40226664 PMCID: PMC11918619 DOI: 10.1155/2024/5586123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 08/24/2024] [Accepted: 09/26/2024] [Indexed: 04/15/2025] Open
Abstract
Background: More than two-thirds of patients with functional gastrointestinal disorders (FGIDs) experience various degrees of mental health issues. Although studies indicate that FGIDs are related to depressive symptoms, sleep disorders, and somatic symptoms, the underlying mechanism between these variables remains unknown. Our objective was to establish a model that outlines the interactions between these psychological dimensions in FGIDs and, thus, provide valuable insights into how to enhance the well-being of affected individuals. Methods: This study used the convenient sampling method to enroll patients who visited the digestive internal medicine department. A total of 238 patients were investigated using the Rome IV criteria (irritable bowel syndrome used Rome Ⅲ criteria). A questionnaire including the Hospital Anxiety and Depressive Symptoms Scale, the Pittsburgh Sleep Quality Index, and the Patient Health Questionnaire-12 was used. The chain mediating roles of sleep disorders and somatic symptoms in the relationship between depressive symptoms and FGIDs were examined by the bootstrap method. Results: Correlation analysis revealed that depressive symptoms were positively related to sleep disorders, somatic symptoms, and FGIDs. Sleep disorders were positively related to somatic symptoms and FGIDs. Somatic symptoms were positively related to FGIDs. Chain mediating effect analysis showed that depressive symptoms can not only affect FGIDs but also through three indirect paths, as follows: the mediating role of sleep disorders and somatic symptoms, the chain mediating roles of sleep disorders and somatic symptoms, and the mediating effect size accounted for 7.2%, 7.7%, and 2.5% of the total effect, respectively. Conclusions: This study is conducive to understanding the internal mechanism underlying the relationship between depressive symptoms and FGIDs. It reminds us that when treating FGIDs patients, we should not only provide adequate psychological support to improve but also pay attention to improvements in their sleep quality and somatic symptoms.
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Affiliation(s)
- Jiana Wang
- School of Public Health, Health Science Center, Ningbo University, No. 818 Fenghua Road, Ningbo 315211, Zhejiang, China
- Department of Social Medicine, School of Health Management, China Medical University, No. 77 Puhe Road, Shenyang, North New Area, Shenyang, Liaoning 110122, China
| | - Nana Meng
- Department of Social Medicine, School of Health Management, China Medical University, No. 77 Puhe Road, Shenyang, North New Area, Shenyang, Liaoning 110122, China
| | - Kun Chen
- Department of Social Medicine, School of Health Management, China Medical University, No. 77 Puhe Road, Shenyang, North New Area, Shenyang, Liaoning 110122, China
| | - Xinyuan Huang
- Department of Social Medicine, School of Health Management, China Medical University, No. 77 Puhe Road, Shenyang, North New Area, Shenyang, Liaoning 110122, China
| | - Lin Feng
- Department of Social Medicine, School of Health Management, China Medical University, No. 77 Puhe Road, Shenyang, North New Area, Shenyang, Liaoning 110122, China
| | - Cong Yang
- Department of Social Medicine, School of Health Management, China Medical University, No. 77 Puhe Road, Shenyang, North New Area, Shenyang, Liaoning 110122, China
| | - Zhe Li
- Anesthesiology Department, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xun Sun
- Department of Immunology, Basic Medicine College, China Medical University, No. 77 Puhe Road, Shenyang, North New Area, Shenyang 110122, Liaoning, China
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Zahid SA, Tated R, Mathew M, Rajkumar D, Karnik SB, Pramod Roy A, Jacob FP, Baskara Salian R, Razzaq W, Shivakumar D, Khawaja UA. Diabetic Gastroparesis and its Emerging Therapeutic Options: A Narrative Review of the Literature. Cureus 2023; 15:e44870. [PMID: 37814758 PMCID: PMC10560130 DOI: 10.7759/cureus.44870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 09/06/2023] [Indexed: 10/11/2023] Open
Abstract
Diabetic gastroparesis (DG) is one of the many complications of diabetes mellitus (DM). Even though this condition surfaces years after uncontrolled disease, it affects the quality of life in several ways and causes significant morbidity. Common symptoms experienced by the patients include postprandial nausea, vomiting, abdominal fullness, and pain. Strict glycemic control is essential to evade the effects of DG. The purpose of this review article is to briefly study the pathophysiology, clinical features, diagnostic modalities, and the effects of DG on different aspects of life. Furthermore, it also focuses on the emerging treatment modalities for DG. Tradipitant and relamorelin are two such treatment options that are gaining noteworthy recognition and are discussed in detail in this review article. As observed through various clinical trials, these drugs help alleviate symptoms like nausea, vomiting, abdominal pain, and bloating in patients suffering from DG, thereby targeting the most common and bothersome symptoms of the disease. This leads to an improvement in the quality of life, making it a reliable treatment option for this disease. But while pharmacological intervention is vital, psychological support and lifestyle changes are equally important and are the reason why a multidisciplinary approach is required for the treatment of DG.
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Affiliation(s)
- Shiza A Zahid
- Department of Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
| | - Ritu Tated
- Department of Internal Medicine, Mahatma Gandhi Mission Institute of Medical Sciences, Navi Mumbai, IND
| | - Midhun Mathew
- Department of Internal Medicine, Pennsylvania Hospital, Philadelphia, USA
| | - Daniel Rajkumar
- Department of Internal Medicine, Hospital Alor Gajah, Alor Gajah, MYS
| | - Siddhant B Karnik
- Department of Internal Medicine, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, IND
| | | | - Fredy P Jacob
- Department of Internal Medicine, Jonelta Foundation School of Medicine, University of Perpetual Help System DALTA, Las Piñas, PHL
| | | | - Waleed Razzaq
- Department of Internal Medicine, Services Hospital Lahore, Lahore, PAK
| | - Divya Shivakumar
- Department of Internal Medicine, Kamineni Academy of Medical Sciences and Research Center, Hyderabad, IND
| | - Uzzam Ahmed Khawaja
- Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, PAK
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Oshima T. Functional Dyspepsia: Current Understanding and Future Perspective. Digestion 2023; 105:26-33. [PMID: 37598673 DOI: 10.1159/000532082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 07/18/2023] [Indexed: 08/22/2023]
Abstract
BACKGROUND Functional dyspepsia (FD) is a common disorder characterized by chronic or recurrent upper abdominal pain or discomfort without any structural abnormalities in the gastrointestinal tract. FD is categorized into two subgroups based on symptoms: postprandial distress syndrome (PDS) and epigastric pain syndrome. SUMMARY The pathophysiology of FD involves several mechanisms. Delayed gastric emptying is observed in approximately 30% of FD patients but does not correlate with symptom patterns or severity. Impaired gastric accommodation is important in the pathophysiology, particularly for PDS. Visceral hypersensitivity, characterized by heightened sensitivity to normal activities, contributes to the perception of discomfort or pain in FD. Alterations to the duodenal mucosa, including impaired mucosal barrier function and low-grade inflammation, are also implicated in the pathogenesis of FD. Microbial dysbiosis and psychological factors such as stress can further exacerbate symptoms. Treatment options include dietary modifications, establishing a physician-patient relationship, acid suppressants, prokinetics, neuromodulators, and behavioral therapies. Dietary recommendations include eating smaller, more frequent meals, and avoiding trigger foods. Acid suppressants are used as the first-line treatment. Prokinetics and neuromodulators aim to improve gastric motility and central pain processing, respectively. Behavioral therapies, including cognitive behavioral therapy and hypnotherapy, have shown benefits for refractory FD. Severe and refractory cases may require combination therapies or experimental treatments. KEY MESSAGES FD is a disorder of gut-brain interaction involving diverse pathophysiological mechanisms. Individualized treatment based on symptoms and responses to interventions is crucial. Further research is needed to improve the understanding of FD and advance the development of effective therapies.
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Affiliation(s)
- Tadayuki Oshima
- Department of Gastroenterology, Okazaki City Medical Association Public Health Center, Okazaki, Japan
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Zheng J, Han J, Wang Y, Tian Z. Role of brain NUCB2/nesfatin-1 in stress and stress-related gastrointestinal disorders. Peptides 2023:171043. [PMID: 37311488 DOI: 10.1016/j.peptides.2023.171043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 06/04/2023] [Accepted: 06/08/2023] [Indexed: 06/15/2023]
Abstract
Since the discovery of NUCB2/nesfatin-1 as a novel anorexigenic factor, the expanding function of this peptide has been elucidated in recent years. Increasing evidence suggests that NUCB2/nesfatin-1 is also involved in the regulation of stress and stress-related gastrointestinal disorders. Therefore, we investigated the relationship between NUCB2/nesfatin-1, stress and stress-related gastrointestinal disorders and summarized the results of these studies. Different stressors and duration of stress activate different NUCB2/nesfatin-1-associated brain regions and have different effects on serum corticosterone levels. Central and peripheral NUCB2/nesfatin-1 mediates stress-related gastrointestinal disorders but appears to be protective against inflammatory bowel disease. NUCB2/nesfatin-1 plays an important role in mediating the brain-gut crosstalk, but precise clarification is still needed to gain more insight into these complex relationships.
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Affiliation(s)
- Jiayuan Zheng
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture Research, Academy of Integrative Medicine, Shanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200433, China
| | - Jing Han
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture Research, Academy of Integrative Medicine, Shanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200433, China
| | - Yu Wang
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture Research, Academy of Integrative Medicine, Shanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200433, China
| | - Zhanzhuang Tian
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture Research, Academy of Integrative Medicine, Shanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200433, China.
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Algera JP, Colomier E, Melchior C, Hreinsson JP, Midenfjord I, Clevers E, Simrén M, Törnblom H. Associations between postprandial symptoms, hydrogen and methane production, and transit time in irritable bowel syndrome. Neurogastroenterol Motil 2023; 35:e14482. [PMID: 36221245 PMCID: PMC10078221 DOI: 10.1111/nmo.14482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 09/05/2022] [Accepted: 09/20/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients. METHODS We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires. KEY RESULTS After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p < 0.05), and more rapid OATT was associated with higher severity of abdominal discomfort, rumbling, nausea, and urgency (p < 0.05 for all) both pre- and post-prandially. Postprandial nausea, urgency, and abdominal pain changed differently over time depending on OATT (p < 0.05 for all). OATT, but not rectal sensitivity, was associated with hydrogen and methane concentrations (p = 0.002 for both). Trajectories over time of postprandial symptoms and exhaled hydrogen/methane concentrations were correlated with different correlations depending on OATT. CONCLUSION AND INFERENCES This study highlights the importance of oroanal transit and hydrogen and methane production in the pathophysiology of IBS and increases our understanding of pathophysiological factors involved in postprandial symptom generation. Treatments targeting oroanal transit and hydrogen and methane production may improve specific postprandial symptoms.
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Affiliation(s)
- Joost P Algera
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Esther Colomier
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Chronic Diseases, Metabolism and Aging (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Chloé Melchior
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Gastroenterology Department and INSERM CIC-CRB 1404, Rouen University Hospital, Rouen, France.,INSERM U1073, Rouen Normandy University, Rouen, France
| | - Jóhann P Hreinsson
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Irina Midenfjord
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Egbert Clevers
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Chronic Diseases, Metabolism and Aging (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Centre for Functional GI & Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Jones MP, Shah A, Walker MM, Koloski NA, Holtmann G, Talley NJ. Overlap of heartburn, functional dyspepsia, and irritable bowel syndrome in a population sample: Prevalence, temporal stability, and associated comorbidities. Neurogastroenterol Motil 2022; 34:e14349. [PMID: 35293084 DOI: 10.1111/nmo.14349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 02/02/2022] [Accepted: 02/22/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Co-occurring (overlapping) irritable bowel syndrome (IBS), functional dyspepsia (FD), and heartburn has been observed. However, whether it is a distinct entity has not been established, nor what clinical, demographic, lifestyle, and psychological traits are associated with it. This study sought to estimate the prevalence and temporal stability of this overlap and to identify features specific to it in order to gain some insights into the potential etiopathogenesis. METHODS Two waves of a survey to a population-representative sample were conducted 3 years apart, recruiting 1312 individuals for this study. The chance-expected probability of complete overlap (CO) was calculated and compared with the observed CO. A range of demographic, lifestyle factors, medical diagnoses, sleep quality, and psychological distress were tested to identify predictors of overlap using logistic regression. KEY RESULTS CO was observed in 2.1% (95% confidence interval 1.9, 3.7) of the sample and was closely replicated in wave 2 at 2.0%. The observed CO was greater than expected by chance (0.2%) to a statistically significant extent (p < 0.001). Overlap between IBS subtypes, FD subtypes, and heartburn was also elevated above chance expectation. Individuals with CO were separately differentiated from others with respect to elevated rates of self-reported medically diagnosed asthma, elevated psychological distress score, and elevated impact on sleep quality. The discrimination provided by these factors was further independent of age and sex. CONCLUSIONS AND INFERENCES Overlap between IBS, FD, and heartburn (GERD) appears to be a distinct entity that has a profile including psychological morbidity, sleep disturbance, and elevated rates of atopy.
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Affiliation(s)
- Michael P Jones
- School of Psychological Sciences, Macquarie University, North Ryde, New South Wales, Australia
| | - Ayesha Shah
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Marjorie M Walker
- College of Health, Medicine and Well Being, University of Newcastle, Newcastle, New South Wales, Australia
| | - Natasha A Koloski
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,College of Health, Medicine and Well Being, University of Newcastle, Newcastle, New South Wales, Australia
| | - Gerald Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Nicholas J Talley
- College of Health, Medicine and Well Being, University of Newcastle, Newcastle, New South Wales, Australia
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Black CJ, Paine PA, Agrawal A, Aziz I, Eugenicos MP, Houghton LA, Hungin P, Overshott R, Vasant DH, Rudd S, Winning RC, Corsetti M, Ford AC. British Society of Gastroenterology guidelines on the management of functional dyspepsia. Gut 2022; 71:1697-1723. [PMID: 35798375 PMCID: PMC9380508 DOI: 10.1136/gutjnl-2022-327737] [Citation(s) in RCA: 79] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/21/2022] [Indexed: 01/30/2023]
Abstract
Functional dyspepsia (FD) is a common disorder of gut-brain interaction, affecting approximately 7% of individuals in the community, with most patients managed in primary care. The last British Society of Gastroenterology (BSG) guideline for the management of dyspepsia was published in 1996. In the interim, substantial advances have been made in understanding the complex pathophysiology of FD, and there has been a considerable amount of new evidence published concerning its diagnosis and classification, with the advent of the Rome IV criteria, and management. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based diagnosis and treatment of patients. The approach to investigating the patient presenting with dyspepsia is discussed, and efficacy of drugs in FD summarised based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of pairwise and network meta-analyses. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system. These provide both the strength of the recommendations and the overall quality of evidence. Finally, in this guideline, we consider novel treatments that are in development, as well as highlighting areas of unmet need and priorities for future research.
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Affiliation(s)
- Christopher J Black
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Peter A Paine
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
- Gastroenterology, Salford Royal NHS Foundation Trust, Salford, UK
| | - Anurag Agrawal
- Doncaster and Bassetlaw Hospitals NHS Trust, Doncaster, UK
| | - Imran Aziz
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Department of Infection, Immunity, and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Maria P Eugenicos
- Department of Gastroenterology, University of Edinburgh, Edinburgh, UK
| | - Lesley A Houghton
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Pali Hungin
- Primary Care and General Practice, University of Newcastle, Newcastle, UK
| | - Ross Overshott
- Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK
| | - Dipesh H Vasant
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
- Neurogastroenterology Unit, Gastroenterology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
| | - Sheryl Rudd
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
- University of Nottingham and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Richard C Winning
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
- University of Nottingham and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
- University of Nottingham and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Alexander C Ford
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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Huang Q, Zheng S, Cai T, Zhang S, Su Q, Wang F. Factors associated with mood disorders and the efficacy of the targeted treatment of functional dyspepsia: A randomized clinical trial. Front Med (Lausanne) 2022; 9:859661. [PMID: 35935797 PMCID: PMC9353185 DOI: 10.3389/fmed.2022.859661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 07/01/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundPatients with functional dyspepsia (FD) are often accompanied by mood disorders (MDs). This study aimed to identify factors associated with MDs in patients with FD and evaluate the efficacy of targeted treatment plans.MethodsRelevant scales were used to assess MDs. Patients with FD having MDs and acid reflux were treated with flupentixol and melitracen (FM) and acid-suppressive therapy (AST) (histamine-2 receptor antagonists (H2RAs) (group A) or proton pump inhibitors (PPIs) (group B)), and those without acid reflux (group C) did not receive AST. Patients with FD without MDs were randomly administered H2RAs (group D) or PPIs (group E). The primary endpoints were factors associated with MDs and improvement in gastrointestinal (GI) symptoms and MDs in patients with FD.ResultsA total of 362 patients with FD were enrolled in this study. Patients with FD having high GI score and low education were found prone to MDs. At week 2, the remission rate of overall GI symptoms and depression was significantly higher in group B than that in groups A and C [GI: 72.72% (32/44) vs. 47.73% (21/44) and 72.72% (32/44) vs. 38.94% (44/113), all P < 0.05; depression: 72.22% (26/36) vs. 41.67% (15/36) and 72.22% (26/36) vs. 41.57% (37/89), all P < 0.05]. Furthermore, the remission rate of overall GI symptoms was significantly higher in group E than that in group D [60.29% (41/68) vs. 42.65% (29/68), P < 0.05]. At week 8, similar efficacies and adverse reactions were observed in these groups.ConclusionThe risk factors for MDs were high GI scores and low literacy rates. Thus, targeted treatment (FM+PPIs for patients with MDs; PPIs for patients without MDs) can improve the efficacy of patients with FD.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2100053126.
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Affiliation(s)
- Qian Huang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
- Hunan Key Laboratory of Non Resolving Inflammation and Cancer, Changsha, China
| | - Shaopeng Zheng
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
- Hunan Key Laboratory of Non Resolving Inflammation and Cancer, Changsha, China
| | - Ting Cai
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
- Hunan Key Laboratory of Non Resolving Inflammation and Cancer, Changsha, China
| | - Suxin Zhang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
- Hunan Key Laboratory of Non Resolving Inflammation and Cancer, Changsha, China
| | - Qian Su
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
- Hunan Key Laboratory of Non Resolving Inflammation and Cancer, Changsha, China
| | - Fen Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
- Hunan Key Laboratory of Non Resolving Inflammation and Cancer, Changsha, China
- *Correspondence: Fen Wang
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10
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WU D, WANG Y, ZHANG JL, LIAN HH, CHEN LQ, PENG T, RONG PJ, HOU LW. Transcutaneous auricular vagus nerve stimulation for functional dyspepsia: A randomized controlled trial. WORLD JOURNAL OF ACUPUNCTURE-MOXIBUSTION 2021. [DOI: 10.1016/j.wjam.2021.05.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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11
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Kao KL, Sung FC, Huang HC, Lin CJ, Chen SC, Lin CL, Huang YP, Wu SI, Chen YS, Stewart R. Functional dyspepsia in depression: A population-based cohort study. Eur J Clin Invest 2021; 51:e13506. [PMID: 33529347 DOI: 10.1111/eci.13506] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 12/22/2020] [Accepted: 01/05/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Patients with functional dyspepsia (FD) are more likely to have persistent depression, yet whether depression and antidepressant treatments are associated with subsequent risk of FD remain unclear. METHODS Using population-based insurance administrative data of Taiwan, an 11-year historic cohort study was assembled, comparing cases aged 18 and above with the diagnosis of depressive disorder, to a propensity score-matched sample of adults without depression. Incident FD as a primary diagnosis was ascertained. Hazard ratios of FD were calculated using Cox regression models by age, gender, other comorbidities, nonsteroidal anti-inflammatory medications, antidepressants and antidiabetic agents. RESULTS A total of 20,197 people with depressive disorder and 20,197 propensity score-matched comparisons without depression were followed up. The incidence of FD was 1.7-fold greater in the depressive cohort than in comparisons (12.9 versus 7.57 per 1000 person-years), with an adjusted hazard ratio (aHR) of 2.16 (95% confidence interval (CI) 1.93~2.41). Increased risks were significant regardless of comorbidities or medication uses, the highest in the untreated depression group compared to the group without depression, with an aHR of 2.51(95% CI 2.15~2.93). CONCLUSIONS This population-based study showed that patients with depressive disorder are at elevated risk of FD. Antidepressant treatment could reduce the risk of FD.
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Affiliation(s)
- Kai-Liang Kao
- Department of Pediatrics, Far Eastern Memorial Hospital, Taipei, Taiwan
| | - Fung-Chang Sung
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.,Department of Health Services Administration, College of Public Health, China Medical University, Taichung, Taiwan.,Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan
| | - Hui-Chun Huang
- Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.,MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
| | - Chen-Ju Lin
- Section of Psychiatry and Suicide Prevention Center, Mackay Memorial Hospital, Taipei, Taiwan
| | - Shu-Chin Chen
- Suicide Prevention Center, Mackay Memorial Hospital, Taipei, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Yo-Ping Huang
- Department of Electrical Engineering, National Taipei University of Technology, Taipei, Taiwan
| | - Shu-I Wu
- Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.,Section of Psychiatry and Suicide Prevention Center, Mackay Memorial Hospital, Taipei, Taiwan.,Department of Medicine, Mackay Medical College, Taipei, Taiwan
| | - Yi-Shin Chen
- Department of Computer Science, National Tsing Hua University, Hsinchu, Taiwan
| | - Robert Stewart
- Service and Population Research Department, King's College, Institute of Psychiatry, Psychology & Neuroscience, London, UK.,South London and Maudsley NHS Foundation Trust, London, UK
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12
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Abstract
OBJECTIVE Functional gastroduodenal symptoms (FGDSs) may result from perturbations in gastric emptying (GE) and gastric accommodation (GA), which are variably affected by acute stress. This study aimed to examine whether individuals who have both mood disorder and FGDS exhibit differences in GE and GA using standardized, validated, and reproducible noninvasive methods. METHODS Using a data retrieval program, 1554 individuals at a single center were identified after having undergone measurements of GE by scintigraphy of a 99mTc-radiolabeled egg (320 kcal, 30% fat meal) and GA by single-photon emission computed tomography to assess the underlying pathophysiology in FGDS. An extensive medical record review identified 267 of these individuals as having diagnoses of depression, anxiety, or comorbid anxiety/depression (CAD). Differences in GE and GA as related to the presence of anxiety or depressive disorders were analyzed using one-way analysis of variance on ranks and Mann-Whitney tests for the two-group comparisons. RESULTS Sixty-three patients with anxiety, 134 with depression, and 70 with CAD were identified. GE at 1 hour was slower (p = .04) and GE at 2 hours numerically decreased (p = .07) for depression compared with anxiety. GA was diminished for CAD compared with anxiety (p = .04) and depression (p = .009). There were no differences in fasting gastric volume or GE at 4 hours. CONCLUSIONS In this study examining GE and GA in anxiety and depressive disorders among patients with FGDS, the combined presence of anxiety and depression was associated with impaired GA compared with patients with depression or anxiety alone, and early GE seemed to be slower in those with depression compared with patients with anxiety.
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13
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Chan Y, Cheong PK, Fang FF, Cheung CKY, Lan LL, Yuen KWK, Ching JYL, Mak ADP, Wu JCY. A symptom severity questionnaire for patients suffering from functional gastrointestinal disorder: FGI-Checklist. J Gastroenterol Hepatol 2020; 35:1130-1135. [PMID: 31734958 DOI: 10.1111/jgh.14937] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 11/01/2019] [Accepted: 11/03/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM A well-validated, comprehensive checklist of functional gastrointestinal (FGI) disorder (FGID) symptom severity for tracking symptom profile changes over time is lacking. We aim to develop and validate a comprehensive symptom severity checklist for FGID. METHODS A 20-item scale, including both upper and lower gastrointestinal symptoms, was generated to measure the symptom severity commonly found in FGID. Patients who experienced at least monthly symptoms of FGID with negative endoscopy findings were invited to complete the FGI-Checklist, Patient Health Questionaire-9 for assessing depressive symptoms, and Patient Health Questionnaire-15 for assessing somatic symptoms at baseline. A subset of patients who met Rome III diagnostic criteria of gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome received medication treatment for 8-12 weeks and completed the FGI-Checklist again at a follow-up visit. Exploratory factor analysis was performed for subscales formation and psychometric properties were measured. RESULTS Six hundred and forty-one patients were recruited for current study and 108 (16.8%) of them completed the FGI-Checklist again at follow-up. Exploratory factor analysis identified a five-factor solution accounting for 66.8% of the total variance. The five factors are named esophageal syndrome, reflux syndrome, functional dyspepsia syndrome, nausea and vomiting syndrome, and abdominal and bowel syndrome. The FGI-Checklist total score correlated with Patient Health Questionaire-9 and Patient Health Questionnaire-15 (all P < 0.001), which demonstrated good construct validity. Good item-internal consistency was found (Cronbach's alphas: 0.69-0.87). Responsiveness for reflux syndrome subscale, functional dyspepsia syndrome subscale, and abdominal and bowel syndrome subscale after medication treatment was significant (paired-t-test: all P < 0.01). CONCLUSION The instrument, Checklist, is valid and reliable.
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Affiliation(s)
- Yawen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Pui Kuan Cheong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Fanny Fan Fang
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Cynthia K Y Cheung
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Lin Lin Lan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Kay Wing Ki Yuen
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | | | - Arthur Dun Ping Mak
- Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong, China
| | - Justin Che-Yuen Wu
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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14
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Kim YS, Kim N. Functional Dyspepsia: A Narrative Review With a Focus on Sex-Gender Differences. J Neurogastroenterol Motil 2020; 26:322-334. [PMID: 32606255 PMCID: PMC7329152 DOI: 10.5056/jnm20026] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 04/11/2020] [Accepted: 05/06/2020] [Indexed: 12/11/2022] Open
Abstract
Functional dyspepsia (FD) is among the most common gastrointestinal disorders affecting quality of life (QoL). As it frequently occurs in women than in men the comparison of various aspects including prevalence, clinical manifestations, and QoL in FD between women and men is very important for understanding the disease distribution and burden, evaluating treatment options, developing new drugs, and allocating medical resources. However, little is known about sex or gender differences among patients with FD. In spite of limited studies, consistent points are that FD occurs more often in women than in men and there are several symptom differences between men and women with FD. In addition, women with FD tend to have lower QoL than men with FD. Similarly, the pathophysiology of FD likely to vary depending on gender. Furthermore, a sex-gender-oriented approach in healthcare system could enhance understanding heterogeneous patients suffering from FD. Due to the sex-gender differences in physiological and psychological factors, treatment strategies should differ between women and men with FD. In conclusion, an individualized and multicomponent approach that considers sex and gender issues might improve FD treatment and improve patient Qol, especially for women.
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Affiliation(s)
- Young Sun Kim
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Nayoung Kim
- Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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15
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Van den Houte K, Scarpellini E, Verbeure W, Mori H, Schol J, Masuy I, Carbone F, Tack J. The Role of GI Peptides in Functional Dyspepsia and Gastroparesis: A Systematic Review. Front Psychiatry 2020; 11:172. [PMID: 32256403 PMCID: PMC7093580 DOI: 10.3389/fpsyt.2020.00172] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 02/21/2020] [Indexed: 12/12/2022] Open
Abstract
Functional dyspepsia (FD) and gastroparesis (GP) are common disorders of the upper gastrointestinal tract. The pathophysiology of these conditions is likely to be heterogenous, and factors such as altered motility, sensitivity and response to nutrition have been identified as putative underlying mechanisms. Motility, sensitivity as well as responses to nutrition can be influenced or mediated by peptide hormones and serotonin released from the gastrointestinal mucosa. This review summarizes the role of GI peptides in functional dyspepsia and gastroparesis. In most studies, the levels of somatostatin, ghrelin, and motilin did not differ between healthy volunteers and FD or GP patients, but higher symptom burden was often correlated with higher peptide levels. Ghrelin and motilin receptor agonists showed promising results in improvement of the gastric emptying, but the link with improvement of symptoms is less predictable. Serotonin agonists have a potential to improve symptoms in both FD and idiopathic gastroparesis. Drugs acting on the GLP-1 and on the PYY receptors deserve further investigation. There is a need for systematic large scale studies.
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Affiliation(s)
| | | | | | | | | | | | | | - Jan Tack
- Translational Research Center for Gastrointestinal Diseases, University of Leuven, Leuven, Belgium
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16
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Accarie A, Vanuytsel T. Animal Models for Functional Gastrointestinal Disorders. Front Psychiatry 2020; 11:509681. [PMID: 33262709 PMCID: PMC7685985 DOI: 10.3389/fpsyt.2020.509681] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Accepted: 10/22/2020] [Indexed: 12/12/2022] Open
Abstract
Functional gastrointestinal disorders (FGID), such as functional dyspepsia (FD) and irritable bowel syndrome (IBS) are characterized by chronic abdominal symptoms in the absence of an organic, metabolic or systemic cause that readily explains these complaints. Their pathophysiology is still not fully elucidated and animal models have been of great value to improve the understanding of the complex biological mechanisms. Over the last decades, many animal models have been developed to further unravel FGID pathophysiology and test drug efficacy. In the first part of this review, we focus on stress-related models, starting with the different perinatal stress models, including the stress of the dam, followed by a discussion on neonatal stress such as the maternal separation model. We also describe the most commonly used stress models in adult animals which brought valuable insights on the brain-gut axis in stress-related disorders. In the second part, we focus more on models studying peripheral, i.e., gastrointestinal, mechanisms, either induced by an infection or another inflammatory trigger. In this section, we also introduce more recent models developed around food-related metabolic disorders or food hypersensitivity and allergy. Finally, we introduce models mimicking FGID as a secondary effect of medical interventions and spontaneous models sharing characteristics of GI and anxiety-related disorders. The latter are powerful models for brain-gut axis dysfunction and bring new insights about FGID and their comorbidities such as anxiety and depression.
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Affiliation(s)
- Alison Accarie
- Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.,Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
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17
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Li H, Buisman-Pijlman FTA, Nunez-Salces M, Christie S, Frisby CL, Inserra A, Hatzinikolas G, Lewis MD, Kritas S, Wong ML, Page AJ. Chronic stress induces hypersensitivity of murine gastric vagal afferents. Neurogastroenterol Motil 2019; 31:e13669. [PMID: 31241809 DOI: 10.1111/nmo.13669] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 05/22/2019] [Accepted: 06/18/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Stress exposure is known to trigger and exacerbate functional dyspepsia (FD) symptoms. Increased gastric sensitivity to food-related stimuli is widely observed in FD patients and is associated with stress and psychological disorders. The mechanisms underlying the hypersensitivity are not clear. Gastric vagal afferents (GVAs) play an important role in sensing meal-related mechanical stimulation to modulate gastrointestinal function and food intake. This study aimed to determine whether GVAs display hypersensitivity after chronic stress, and whether its interaction with leptin was altered by stress. METHODS Eight-week-old male C57BL/6 mice were exposed to unpredictable chronic mild stress or no stress (control) for 8 weeks. The metabolic rate, gastric emptying rate, and anxiety- and depression-like behaviors were determined. GVA mechanosensitivity, and its modulation by leptin, was determined using an in vitro single fiber recording technique. QRT-PCR was used to establish the levels of leptin and leptin receptor mRNA in the stomach and nodose ganglion, respectively. KEY RESULTS The stressed mice had lower body weight and food intake, and increased anxiety-like behavior compared to the control mice. The mechanosensitivity of mucosal and tension-sensitive GVAs was higher in the stressed mice. Leptin potentiated mucosal GVA mechanosensitivity in control but not stressed mice. The expression of leptin mRNA in the gastric mucosa was lower in the stressed mice. CONCLUSIONS AND INFERENCES In conclusion, chronic stress enhances GVA mechanosensitivity, which may contribute to the gastric hypersensitivity in FD. In addition, the modulatory effect of leptin on GVA signaling is lost after chronic stress exposure.
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Affiliation(s)
- Hui Li
- Vagal Afferent Research Group, Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.,Nutrition, Diabetes and Metabolism, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Femke T A Buisman-Pijlman
- Behavioural Neuroscience, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Maria Nunez-Salces
- Vagal Afferent Research Group, Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.,Nutrition, Diabetes and Metabolism, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Stewart Christie
- Vagal Afferent Research Group, Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.,Nutrition, Diabetes and Metabolism, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Claudine L Frisby
- Vagal Afferent Research Group, Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.,Nutrition, Diabetes and Metabolism, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Antonio Inserra
- Neuropsychiatric Laboratory of Mental Health Disorder, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - George Hatzinikolas
- Vagal Afferent Research Group, Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.,Nutrition, Diabetes and Metabolism, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Martin D Lewis
- Neuropsychiatric Laboratory of Mental Health Disorder, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.,School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.,College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
| | - Stamatiki Kritas
- Women's and Children's Hospital, North Adelaide, South Australia, Australia
| | - Ma-Li Wong
- Neuropsychiatric Laboratory of Mental Health Disorder, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Amanda J Page
- Vagal Afferent Research Group, Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.,Nutrition, Diabetes and Metabolism, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
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18
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Howard K, Giblin M, Medina R. The relationship between occupational stress and gastrointestinal illness: A comprehensive study of public schoolteachers. JOURNAL OF WORKPLACE BEHAVIORAL HEALTH 2019. [DOI: 10.1080/15555240.2018.1542310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- Krista Howard
- Department of Psychology, Texas State University, San Marcos, Texas, USA
| | - Madeline Giblin
- Department of Psychology, Texas State University, San Marcos, Texas, USA
| | - Rachel Medina
- Department of Psychology, Texas State University, San Marcos, Texas, USA
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19
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Van Den Houte K, Carbone F, Tack J. Postprandial distress syndrome: stratification and management. Expert Rev Gastroenterol Hepatol 2019; 13:37-46. [PMID: 30791841 DOI: 10.1080/17474124.2019.1543586] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Functional dyspepsia (FD), defined by the Rome consensus as the presence of functional symptoms originating from the gastroduodenum, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. We used a literature search for a narrative review on the current state of knowledge regarding PDS. Areas covered: Epidemiological studies support PDS as a separate entity and the biggest FD subgroup. The pathophysiology of PDS is heterogeneous, and disorders of gastric sensorimotor function as well as low grade duodenal inflammation have been implicated. Although prokinetic agents may provide the most pathophysiology-oriented treatment option, there is a paucity of suitable agents, and proton pump inhibitors are the traditional first-line therapy. Other options include agents that enhance gastric accommodation, such as acotiamide and 5-HT1A agonists, neuromodulators such as mirtazapine, and traditional medicine approaches. Expert commentary: PDS is highly prevalent, with probably heterogeneous underlying pathophysiology. Motility modifying agents and neuromodulators are the cornerstone of PDS therapy, but there is a need for high quality studies of new therapeutic approaches.
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Affiliation(s)
- Karen Van Den Houte
- a Translational Research Center for Gastrointestinal Diseases (TARGID) , University of Leuven , Leuven , Belgium
| | - Florencia Carbone
- a Translational Research Center for Gastrointestinal Diseases (TARGID) , University of Leuven , Leuven , Belgium
| | - Jan Tack
- a Translational Research Center for Gastrointestinal Diseases (TARGID) , University of Leuven , Leuven , Belgium
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20
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Pohl D, Van Oudenhove L, Törnblom H, Le Nevé B, Tack J, Simrén M. Functional Dyspepsia and Severity of Psychologic Symptoms Associate With Postprandial Symptoms in Patients With Irritable Bowel Syndrome. Clin Gastroenterol Hepatol 2018; 16:1745-1753.e1. [PMID: 29702295 DOI: 10.1016/j.cgh.2018.04.034] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 03/18/2018] [Accepted: 04/13/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with irritable bowel syndrome (IBS) have an increased response of postprandial symptoms to a combined lactulose nutrient challenge test, compared with healthy volunteers. We investigated the associations among comorbid functional dyspepsia (FD), severity of psychologic symptoms, and breath test results in response to this test. METHODS We performed a prospective study of 205 patients with IBS (Rome III criteria), 94 of whom also had FD (IBS-FD), and 83 healthy volunteers in Sweden from 2008 through 2015. All participants completed a breath hydrogen test after a 400-mL liquid meal with 25 g lactulose. Gastrointestinal (GI) symptom severity was assessed using a graded scale and digestive comfort was recorded before the meal and every 15 minutes until 240 minutes after the meal. GI symptom scores over time were compared between groups using linear mixed models with anxiety, depression, and somatization as covariates. RESULTS Average levels of all GI symptoms varied over time among all groups (P < .0001). Patients with IBS-FD had higher levels of bloating (P = .004), abdominal pain (P = .005), and lower levels of digestive comfort (P < .01) than patients with only IBS. We observed a difference in increase in abdominal pain from baseline between IBS-FD and IBS groups (P = .013). Anxiety levels were associated with levels of all symptoms (all P < .025) except abdominal pain, which was associated with somatization severity (P < .0001). Furthermore, anxiety levels associated with level of exhaled hydrogen (P = .0042). CONCLUSIONS In a prospective study of patients with IBS, we found those with FD to have increased GI symptoms before and after a liquid meal with lactulose. Anxiety and somatization have an independent additional effect. The presence of comorbid FD and levels of psychologic symptoms affect reports of food-related symptoms in patients with IBS. ClinicalTrial.gov no: NCT01252550.
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Affiliation(s)
- Daniel Pohl
- Functional Diagnostics Laboratory, Division of Gastroenterology, University Hospital Zurich, Zurich, Switzerland.
| | - Lukas Van Oudenhove
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Belgium
| | - Hans Törnblom
- Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Sweden
| | | | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Belgium
| | - Magnus Simrén
- Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Sweden; Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina
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21
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Tack J, Camilleri M. New developments in the treatment of gastroparesis and functional dyspepsia. Curr Opin Pharmacol 2018; 43:111-117. [PMID: 30245474 DOI: 10.1016/j.coph.2018.08.015] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 08/26/2018] [Accepted: 08/28/2018] [Indexed: 12/12/2022]
Abstract
Functional dyspepsia (FD) and gastroparesis are frequent causes of upper gastrointestinal symptoms such as postprandial fullness, early satiation, epigastric pain or burning, upper abdominal bloating, bothersome belching, nausea and vomiting. The underlying pathophysiological mechanisms are heterogeneous and involved mechanisms such as abnormal gastric motility (accommodation, emptying), visceral hypersensitivity, low grade mucosal inflammation and cellular changes in enteric nerves, muscle or interstitial cells of Cajal. Patient-reported outcomes for evaluating treatment efficacy in these conditions were recently developed and validated. Prokinetic agents, which enhance gastric motility, are used for treating both gastroparesis and FD. In FD, besides acid suppressive therapy and Helicobacter pylori eradication, neuromodulators and drugs that enhance gastric accommodation can be applied. In gastroparesis, anti-emetics may also provide symptom relief. Novel approaches under evaluation in these conditions are the fundus relaxing agents acotiamide and buspirone and the antidepressant mirtazapine in FD. For gastroparesis, recently studied agents include the prokinetic ghrelin agonist relamorelin, the prokinetic serotonergic agents velusetrag and prucalopride, the anti-emetic aprepitant and per-endoscopic pyloric myotomy procedures.
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Affiliation(s)
- Jan Tack
- TARGID, University Hospital, Leuven, Belgium.
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22
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Abstract
Gastroparesis is defined as a combination of chronic dyspeptic symptoms and delayed emptying of a solid test meal. It remains a difficult-to-treat disorder with a significant impact on quality of life. Although gastroparesis is defined by delayed emptying, several important studies did not find a correlation between this biomarker and symptom severity or treatment success. Thus, some of the more recent trials explored strategies that ranged from antiemetics to antidepressants. Although dietary management showed benefit, most of the other interventions were barely superior to placebo or were not superior at all. Placebo responses were often quite high and this complicates the assessment of active agents. While it complicates the design and interpretation of clinical trials, high response rates for active and sham interventions indicate that we can achieve symptom relief in many patients and thus give them some reassurance. If indeed most therapies are only marginally better than placebo, the differences in adverse effects should be weighed more strongly, a point that is especially important in view of the controversy surrounding metoclopramide. Mechanistic studies introduced the network of macrophages as another potentially important player in the development of gastroparesis. Results are too preliminary and are largely based on preclinical data but show up- and downregulation of cellular elements controlling gastric function. Thus, future developments may teach us how they interfere with some of these mechanisms in clinical settings, potentially making gastroparesis a reversible process.
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Affiliation(s)
| | - Klaus Bielefeldt
- Division of Gastroenterology, University of Utah, UT, USA.,Gastroenterology Section, George E. Wahlen Department of Veterans Affairs Medical Center, 500 Foothill Drive, Salt Lake City, UT 84103, USA
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23
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Grinsvall C, Törnblom H, Tack J, Van Oudenhove L, Simrén M. Relationships between psychological state, abuse, somatization and visceral pain sensitivity in irritable bowel syndrome. United European Gastroenterol J 2018; 6:300-309. [PMID: 29511560 PMCID: PMC5833221 DOI: 10.1177/2050640617715851] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 05/22/2017] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Psychological states may interfere with visceral sensitivity. Here we investigate associations between psychosocial factors and visceral sensitivity in irritable bowel syndrome (IBS). METHODS Two IBS patient cohorts (Cohort 1: n = 231, Rome II; Cohort 2: n = 141, Rome III) underwent rectal barostat testing, and completed questionnaires for anxiety, depression, somatization, and abuse. The associations between questionnaire measures and visceral sensitivity parameters were analyzed in three-step general linear models (step1: demographic and abuse variables; step 2: anxiety and depression; step 3: somatization). RESULTS Cohort 1. Pain threshold was positively associated with age and female gender, and negatively with adult sexual abuse and somatization. Pain referral area was negatively associated with age and positively with somatization and GI-specific anxiety, the latter effect mediated by somatization. Cohort 2. Pain threshold was positively associated with age and male gender, and negatively with adult sexual abuse. Pain intensity ratings were positively associated with somatization, female gender and depression, the latter effect mediated by somatization. CONCLUSION Somatization is associated with most visceral sensitivity parameters, and mediates the effect of some psychological factors on visceral sensitivity. It may reflect a psychobiological sensitization process driving symptom generation in IBS. In addition, abuse history was found to independently affect some visceral sensitivity parameters.
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Affiliation(s)
- Cecilia Grinsvall
- Department of Internal Medicine &
Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of
Gothenburg, Gothenburg, Sweden
| | - Hans Törnblom
- Department of Internal Medicine &
Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of
Gothenburg, Gothenburg, Sweden
| | - Jan Tack
- Translational Research Center for
Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Lukas Van Oudenhove
- Translational Research Center for
Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Magnus Simrén
- Department of Internal Medicine &
Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of
Gothenburg, Gothenburg, Sweden
- Center for Functional Gastrointestinal
and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill,
NC, USA
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Ye Y, Wang XR, Zheng Y, Yang JW, Yang NN, Shi GX, Liu CZ. Choosing an Animal Model for the Study of Functional Dyspepsia. Can J Gastroenterol Hepatol 2018; 2018:1531958. [PMID: 29623262 PMCID: PMC5830275 DOI: 10.1155/2018/1531958] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Accepted: 11/16/2017] [Indexed: 02/06/2023] Open
Abstract
Functional dyspepsia (FD) is a common functional gastrointestinal disorder with pain or discomfort in the upper abdomen as the main characteristic. The prevalence of FD worldwide varies between 5% and 11%. This condition adversely affects attendance and productivity in the workplace. Emerging evidence is beginning to unravel the pathophysiologies of FD, and new data on treatment are helping to guide evidence-based practice. In order to better understand the pathophysiologies of FD and explore better treatment options, various kinds of animal models of FD have been developed. However, it is unclear which of these models most closely mimic the human disease. This review provides a comprehensive overview of the currently available animal models of FD in relationship to the clinical features of the disease. The rationales, methods, merits, and disadvantages for modelling specific symptoms of FD are discussed in detail.
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Affiliation(s)
- Yang Ye
- Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Xue-Rui Wang
- Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China
| | - Yang Zheng
- Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China
| | - Jing-Wen Yang
- Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China
| | - Na-Na Yang
- Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Guang-Xia Shi
- Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China
| | - Cun-Zhi Liu
- Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China
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25
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Simrén M, Törnblom H, Palsson OS, van Tilburg MAL, Van Oudenhove L, Tack J, Whitehead WE. Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts. Gut 2018; 67:255-262. [PMID: 28104632 DOI: 10.1136/gutjnl-2016-312361] [Citation(s) in RCA: 170] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 12/16/2016] [Accepted: 01/01/2017] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms. DESIGN We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression. RESULTS In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial η2: 0.047-0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05). CONCLUSIONS A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.
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Affiliation(s)
- Magnus Simrén
- Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Hans Törnblom
- Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Olafur S Palsson
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Miranda A L van Tilburg
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Lukas Van Oudenhove
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - William E Whitehead
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Lee IS, Preissl H, Giel K, Schag K, Enck P. Attentional and physiological processing of food images in functional dyspepsia patients: A pilot study. Sci Rep 2018; 8:1388. [PMID: 29362408 PMCID: PMC5780505 DOI: 10.1038/s41598-017-19112-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 12/21/2017] [Indexed: 02/08/2023] Open
Abstract
The food-related behavior of functional dyspepsia has been attracting more interest of late. This pilot study aims to provide evidence of the physiological, emotional, and attentional aspects of food processing in functional dyspepsia patients. The study was performed in 15 functional dyspepsia patients and 17 healthy controls after a standard breakfast. We measured autonomic nervous system activity using skin conductance response and heart rate variability, emotional response using facial electromyography, and visual attention using eyetracking during the visual stimuli of food/non-food images. In comparison to healthy controls, functional dyspepsia patients showed a greater craving for food, a decreased intake of food, more dyspeptic symptoms, lower pleasantness rating of food images (particularly of high fat), decreased low frequency/high frequency ratio of heart rate variability, and suppressed total processing time of food images. There were no significant differences of skin conductance response and facial electromyography data between groups. The results suggest that high level cognitive functions rather than autonomic and emotional mechanisms are more liable to function differently in functional dyspepsia patients. Abnormal dietary behavior, reduced subjective rating of pleasantness and visual attention to food should be considered as important pathophysiological characteristics in functional dyspepsia.
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Affiliation(s)
- In-Seon Lee
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University of Tübingen, Tübingen, Germany
- IMPRS for Cognitive and Systems Neuroscience, Tübingen, Germany
| | - Hubert Preissl
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany Center for Diabetes Research (DZD), Department of Internal Medicine IV, Tübingen, Germany
- Department of Pharmacy and Biochemistry, Institute of Pharmaceutical Sciences, University of Tübingen, Tübingen, Germany
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
| | - Katrin Giel
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University of Tübingen, Tübingen, Germany
| | - Kathrin Schag
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University of Tübingen, Tübingen, Germany
| | - Paul Enck
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University of Tübingen, Tübingen, Germany.
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Jing FC, Zhang J, Feng C, Nian YY, Wang JH, Hu H, Yang BD, Sun XM, Zheng JY, Yin XR. Potential rat model of anxiety-like gastric hypersensitivity induced by sequential stress. World J Gastroenterol 2017; 23:7594-7608. [PMID: 29204059 PMCID: PMC5698252 DOI: 10.3748/wjg.v23.i42.7594] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 10/04/2017] [Accepted: 10/18/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a rat model of anxiety-like gastric hypersensitivity (GHS) of functional dyspepsia (FD) induced by novel sequential stress.
METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood (8 wk) at which point the anxiety-like behaviors and visceromotor responses to gastric distention (20-100 mmHg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1A receptor (5-HT1AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.
RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequential-stress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT (51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA (2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF (304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1 (1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT (47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF (257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it (1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT (41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF (226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site (1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC (Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB (0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01) (n = 8 in each group).
CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.
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Affiliation(s)
- Fu-Chun Jing
- Department of Gastroenterology, Second Hospital Affiliated to the Medical School of Xi’an Jiao Tong University, Xi’an 710004, Shaanxi Province, China
- Department of Digestive Diseases, Baoji People’s Hospital Affiliated to the Medical School of Yan’an University, Baoji 721000, Shaanxi Province, China
| | - Jun Zhang
- Department of Gastroenterology, Second Hospital Affiliated to the Medical School of Xi’an Jiao Tong University, Xi’an 710004, Shaanxi Province, China
| | - Chen Feng
- Department of Gastroenterology, Second Hospital Affiliated to the Medical School of Xi’an Jiao Tong University, Xi’an 710004, Shaanxi Province, China
| | - Yuan-Yuan Nian
- Department of Gastroenterology, Second Hospital Affiliated to the Medical School of Xi’an Jiao Tong University, Xi’an 710004, Shaanxi Province, China
| | - Jin-Hai Wang
- Department of Gastroenterology, Second Hospital Affiliated to the Medical School of Xi’an Jiao Tong University, Xi’an 710004, Shaanxi Province, China
| | - Hao Hu
- Department of Pharmacology, Health Science Center, Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China
- Basic Medical Experiment Teaching Center, Health Science Center, Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China
| | - Bao-De Yang
- Department of Pharmacology, Health Science Center, Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China
- Basic Medical Experiment Teaching Center, Health Science Center, Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China
| | - Xiao-Ming Sun
- Department of Pharmacology, Health Science Center, Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China
- Basic Medical Experiment Teaching Center, Health Science Center, Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China
| | - Jian-Yun Zheng
- Department of Pathology, the First Affiliated Hospital of Xi’an Medical University, Xi’an 710077, Shaanxi Province, China
| | - Xiao-Ran Yin
- Department of Gastroenterology, Second Hospital Affiliated to the Medical School of Xi’an Jiao Tong University, Xi’an 710004, Shaanxi Province, China
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Abstract
Functional dyspepsia is one of the most prevalent functional gastrointestinal disorders. Functional dyspepsia comprises three subtypes with presumed different pathophysiology and aetiology: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS) and a subtype with overlapping PDS and EPS features. Functional dyspepsia symptoms can be caused by disturbed gastric motility (for example, inadequate fundic accommodation or delayed gastric emptying), gastric sensation (for example, sensations associated with hypersensitivity to gas and bloating) or gastric and duodenal inflammation. A genetic predisposition is probable but less evident than in other functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Psychiatric comorbidity and psychopathological state and trait characteristics could also play a part, although they are not specific to functional dyspepsia and are less pronounced than in IBS. Possible differential diagnoses include Helicobacter pylori infection and peptic ulceration. Pharmacological therapy is mostly based on the subtype of functional dyspepsia, such as prokinetic and fundus-relaxing drugs for PDS and acid-suppressive drugs for EPS, whereas centrally active neuromodulators and herbal drugs play a minor part. Psychotherapy is effective only in a small subset of patients, whereas quality of life can be severely affected in nearly all patients. Future therapies might include novel compounds that attempt to treat the underlying gastric and duodenal inflammation.
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29
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Xin X, Lin H, Ren L. Metabonomics research of functional dysplasia of hepatic stagnation and spleen deficiency type. Shijie Huaren Xiaohua Zazhi 2017; 25:2591-2596. [DOI: 10.11569/wcjd.v25.i29.2591] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Functional dyspepsia (FD) is a common digestive disease that is associated with many psychological factors. Modern medicine considers that the pathogenesis of FD is closely related to the effects of the brain-gut axis on the digestive system, but there is still a lack of objective biomarkers for the diagnosis and evaluation of this disease. In recent years, the application of metabonomics to study the pathological changes of metabolites has become a hot spot. Traditional Chinese medicine considered that hepatic stagnation and spleen deficiency is largely responsible for the pathogenesis of FD. The metabonomics study of FD coincides with the concept of holisms and the principle of treatment based on syndrome differentiation in TCM. Nowadays, great progress has been made in the intervention of metabolites changes by acupuncture, Chinese herbal medicine and other methods. This paper will review the recent progress in the metabonomics research of functional dysplasia of hepatic stagnation and spleen deficiency type.
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Affiliation(s)
- Xin Xin
- Liaoning Traditional Chinese Medicine University, Shenyang 110847, Liaoning Province, China,Shenyang Mental Health Center, Shenyang 110168, Liaoning Province, China
| | - Hui Lin
- Liaoning Traditional Chinese Medicine University, Shenyang 110847, Liaoning Province, China
| | - Lu Ren
- Liaoning Traditional Chinese Medicine University, Shenyang 110847, Liaoning Province, China
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Choung RS, Locke GR, Schleck CD, Zinsmeister AR, Talley NJ. Multiple functional gastrointestinal disorders linked to gastroesophageal reflux and somatization: A population-based study. Neurogastroenterol Motil 2017; 29:10.1111/nmo.13041. [PMID: 28256048 PMCID: PMC5730281 DOI: 10.1111/nmo.13041] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 01/09/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND It is unknown why functional gastrointestinal disorders (FGIDs) overlap and limited information exists on risk factors for those with overlap. Our aim was to estimate the prevalence of combinations of FGIDs including reflux (FGIDs-gastroesophageal reflux [GER]), and evaluate potential risk factors for people with multiple disorders in a representative US community. METHODS A population-based study was conducted by mailing a valid GI symptom questionnaire to an age- and gender-stratified random sample of residents of Olmsted County, MN. Rome III definitions were used to identify people with FGIDs, and GER was defined by weekly or more frequent heartburn or acid regurgitation. The prevalence of people meeting multiple symptom complexes was estimated. Moreover, potential risk factors for people with multiple disorders were evaluated. KEY RESULTS A total of 3548 people provided data for each of the necessary symptom questions (mean age: 61±16 years, 54% female). Among these 3548 subjects, 2009 (57%) had no FGIDs-GER, 906 (26%) had a pure FGID-GER, 372 (10%) had 2 FGIDs-GER, and 261 (7%) had 3 or more FGIDs-GER. Somatization as assessed by a higher Somatic Symptom Checklist score (OR=3.3, 95% CI [2.7,4.1]) was associated with an increased odds for those with 3 or more FGIDs-GER compared to subjects with a pure FGID-GER adjusting for age and gender. CONCLUSIONS AND INFERENCES Symptom complex overlap is common rather than rare in the community. GER is an integral symptom complex associated with both upper and lower FGIDs. Somatization is a strong risk factor for multiple FGIDs.
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Affiliation(s)
- Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - G. Richard Locke
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Cathy D. Schleck
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Alan R. Zinsmeister
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
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Woodhouse S, Hebbard G, Knowles SR. Psychological controversies in gastroparesis: A systematic review. World J Gastroenterol 2017; 23:1298-1309. [PMID: 28275310 PMCID: PMC5323455 DOI: 10.3748/wjg.v23.i7.1298] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Revised: 01/18/2017] [Accepted: 02/08/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review literature addressing three key psychologically-oriented controversies associated with gastroparesis.
METHODS A comprehensive search of PubMed, CINAHL, and PsycINFO databases was performed to identify literature addressing the relationship between gastroparesis and psychological factors. Two researchers independently screened all references. Inclusion criteria were: an adult sample of gastroparesis patients, a quantitative methodology, and at least one of the following: (1) evaluation of the prevalence of psychopathology; (2) an outcome measure of anxiety, depression, or quality of life; and (3) evidence of a psychological intervention. Case studies, review articles, and publications in languages other than English were excluded from the current review.
RESULTS Prevalence of psychopathology was evaluated by three studies (n = 378), which found that combined anxiety/depression was present in 24% of the gastroparesis cohort, severe anxiety in 12.4%, depression in 21.8%-23%, and somatization in 50%. Level of anxiety and depression was included as an outcome measure in six studies (n = 1408), and while limited research made it difficult to determine the level of anxiety and depression in the cohort, a clear positive relationship with gastroparesis symptom severity was evident. Quality of life was included as an outcome measure in 11 studies (n = 2076), with gastroparesis patients reporting lower quality of life than population norms, and a negative relationship between quality of life and symptom severity. One study assessed the use of a psychological intervention for gastroparesis patients (n = 120) and found that depression and gastric function were improved in patients who received psychological intervention, however the study had considerable methodological limitations.
CONCLUSION Gastroparesis is associated with significant psychological distress and poor quality of life. Recommendations for future studies and the development of psychological interventions are provided.
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Abstract
Functional dyspepsia (FD) is considered to be a series of integrated responses to dysfunction of the brain-gut axis caused by a combination of biological factors and socio-psychological factors. Gastrointestinal motility disorder and mental emotional disorder are important factors leading to the development of FD, and abnormal function of the brain-gut axis is the core mechanism of FD pathogenesis. The high incidence of FD has caused a high degree of attention. In this paper, we will review the latest advances in the understanding of the pathogenesis of FD and in its treatment.
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Association of Psychological Characteristics and Functional Dyspepsia Treatment Outcome: A Case-Control Study. Gastroenterol Res Pract 2016; 2016:5984273. [PMID: 27547220 PMCID: PMC4980513 DOI: 10.1155/2016/5984273] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 07/03/2016] [Indexed: 12/20/2022] Open
Abstract
This study was to investigate the association of psychological characteristics and functional dyspepsia treatment outcome. 109 patients who met the criteria for FD were enrolled. Eysenck Personality Questionnaire (EPQ), Symptom Checklist 90 (SCL90), and the Pittsburgh Sleep Quality Index (PSQI) were used to measure personality, psychological symptoms, and sleep quality in our patients. Leeds Dyspepsia Questionnaire (LDQ) was used to assess dyspeptic symptoms at baseline and after eight weeks of treatment. The LDQ scores change after therapy, and the degraded rate of LDQ was used to assess the prognosis of patients. Logistic regression model was used to assess the effect of the personality, psychological symptoms, and sleep quality on the prognosis of patients. Our result revealed that poor sleep quality (OR = 7.68, 95% CI 1.83–32.25) and bad marriage status (OR = 1.22, 95% CI 1.10–1.36) had the negative effect on the prognosis of FD, while extroversion in personality traits (OR = 0.86, 95% CI 0.76–0.96) had positive effect on the prognosis of FD. We should pay attention to the sleep quality, the personality, and the marriage status of FD patients; psychological intervention may have benefit in refractory FD.
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34
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Elsenbruch S, Enck P. Psychobiologische Mechanismen bei der Pathophysiologie chronischer viszeraler Schmerzen. Schmerz 2016; 30:407-411. [DOI: 10.1007/s00482-016-0130-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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The Efficacy of Mentha longifolia in the Treatment of Patients With Postprandial Distress Syndrome: A Double-Blind, Randomized Clinical Trial. IRANIAN RED CRESCENT MEDICAL JOURNAL 2016. [DOI: 10.5812/ircmj.34538] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Tominaga K, Fujikawa Y, Tanaka F, Kamata N, Yamagami H, Tanigawa T, Watanabe T, Fujiwara Y, Arakawa T. Structural changes in gastric glial cells and delayed gastric emptying as responses to early life stress and acute adulthood stress in rats. Life Sci 2016; 148:254-9. [DOI: 10.1016/j.lfs.2016.02.025] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 01/27/2016] [Accepted: 02/08/2016] [Indexed: 12/12/2022]
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Oudenhove LV, Levy RL, Crowell MD, Drossman DA, Halpert AD, Keefer L, Lackner JM, Murphy TB, Naliboff BD. Biopsychosocial Aspects of Functional Gastrointestinal Disorders. Gastroenterology 2016; 150:S0016-5085(16)00218-3. [PMID: 27144624 PMCID: PMC8809487 DOI: 10.1053/j.gastro.2016.02.027] [Citation(s) in RCA: 307] [Impact Index Per Article: 34.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 02/11/2016] [Indexed: 12/15/2022]
Abstract
In this paper, we provide a general framework for understanding the functional gastrointestinal disorders (FGID) 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 the FGID. 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 which 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 FGID.
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Affiliation(s)
- Lukas Van Oudenhove
- Laboratory for Brain-Gut Axis Studies, Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Rona L. Levy
- Behavioral Medicine Research Group, School of Social Work, University of Washington, Seattle, Washington
| | - Michael D. Crowell
- Department of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona
| | - Douglas A. Drossman
- Center for Education and Practice of Biopsychosocial Care LLC, Drossman Gastroenterology PLLC, Chapel Hill, North Carolina
| | - Albena D. Halpert
- Center for Digestive Disorders, Boston Medical Center, Pentucket Medical Associates, Haverhill, Massachusetts
| | - Laurie Keefer
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jeffrey M. Lackner
- Behavioral Medicine Clinic, Department of Medicine, University at Buffalo School of Medicine and Biomedical Sciences, State University of New York, New York
| | - Tasha B. Murphy
- Behavioral Medicine Research Group, School of Social Work, University of Washington, Seattle, Washington
| | - Bruce D. Naliboff
- Center for Neurobiology of Stress, Departments of Medicine and Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, California
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Acute Anxiety and Anxiety Disorders Are Associated With Impaired Gastric Accommodation in Patients With Functional Dyspepsia. Clin Gastroenterol Hepatol 2015; 13:1584-91.e3. [PMID: 25869636 DOI: 10.1016/j.cgh.2015.03.032] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 03/19/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Functional dyspepsia (FD) is associated with impaired gastric accommodation, as well as gastric hypersensitivity, delayed emptying, and psychosocial comorbidities. In healthy people, acute anxiety impairs gastric accommodation, which is traditionally quantified as the average increase in gastric volume after a meal over 1 hour. However, this quantification approach does not address the complex time course of the gastric accommodation response to a meal. We modeled gastric accommodation in patients with FD as a function of postprandial time, to investigate whether it is associated with psychosocial factors (state anxiety, anxiety disorder, depression) and gastric sensorimotor function (sensitivity, emptying). METHODS We studied gastric sensorimotor function in 259 consecutive patients diagnosed with FD based on Rome II at the University Hospitals Leuven from January 2002 through February 2009. Subjects underwent a gastric barostat and breath test; psychiatric comorbidity was assessed by questionnaires. Subjects completed the State-Trait Anxiety Inventory to measure levels of state anxiety immediately before and after gastric barostat analysis. The time course of the accommodation response was analyzed using mixed models. Psychological and sensorimotor variables were added to the model as continuous (state anxiety) or dichotomous (gastric sensitivity and emptying, anxiety disorders, depression) covariates, including their interaction with the time effects. RESULTS In subjects with FD, delayed emptying (β = 50.3 ± 15.9; P = .002) and lower state anxiety (β = -1.7 ± 0.7; P = .012) were associated with an upward shift of the accommodation curve. There was a significant interaction between comorbid anxiety disorder and linear (β = 8.2 ± 3.5; P = .02), quadratic (β = -0.4 ± 0.1; P = .004), and cubic (β = 0.005 ± 0.002; P = .002) effects of time: patients with a comorbid anxiety disorder had significantly slower initial increases in gastric volume to a lower maximum, and a slower return to baseline, compared with patients without anxiety disorder. Depression and gastric sensitivity were not associated significantly with gastric accommodation. CONCLUSIONS In patients with FD, state anxiety and comorbid anxiety disorders are associated with impaired accommodation; gastric emptying also is associated with accommodation in these patients. These findings help elucidate the complex interactions between psychological processes and disorders, gastric sensorimotor dysfunction, and symptom reporting in patients with FD.
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Oshima T, Fukui H, Watari J, Miwa H. Childhood abuse history is associated with the development of dyspepsia: a population-based survey in Japan. J Gastroenterol 2015; 50:744-50. [PMID: 25416144 DOI: 10.1007/s00535-014-1014-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2014] [Accepted: 11/04/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Functional dyspepsia (FD) is a heterogeneous disorder, and it is not clear whether childhood abuse influences the severity of dyspeptic symptoms and the type of dyspepsia. Accordingly, we administered a questionnaire survey to evaluate the association of abuse history in the development of dyspepsia. METHODS Study subjects were selected from among a panel of volunteers, to make equal distribution of age, sex, and residential area. A Web-based questionnaire was administered to uninvestigated dyspepsia subjects who had obtained a consultation at a medical institute, dyspepsia subjects who had not, and healthy control subjects. Dyspepsia was categorized into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) using the Rome III adult FGID questionnaire. Physical, sexual, and psychological abuse history and severity of dyspeptic symptoms were assessed by a questionnaire. RESULTS Each type of abuse was significantly prevalent in uninvestigated dyspepsia subjects. Childhood abuse history was significantly prevalent in dyspepsia. However, these abuse histories were not associated with consultation behavior. Childhood abuse was more prevalent in subjects with dyspepsia and in females. Severity of dyspeptic symptoms was significantly greater in dyspepsia subjects with a history of abuse. Childhood abuse was more prevalent in dyspepsia subjects with the overlap of EPS and PDS and in those who also had irritable bowel syndrome (IBS). CONCLUSIONS Childhood abuse history was associated with the development of dyspepsia especially in the overlapping diagnoses of EPS and PDS, and overlapping with IBS but not with consultation behavior. Abuse history should be assessed in the care of patients with dyspepsia.
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Affiliation(s)
- Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan,
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Abdel-Aziz H, Wadie W, Zaki HF, Müller J, Kelber O, Efferth T, Khayyal MT. Novel sequential stress model for functional dyspepsia: Efficacy of the herbal preparation STW5. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2015; 22:588-595. [PMID: 25981926 DOI: 10.1016/j.phymed.2015.03.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Revised: 03/19/2015] [Accepted: 03/19/2015] [Indexed: 06/04/2023]
Abstract
BACKGROUND Many screening procedures for agents with potential usefulness in functional dyspepsia (FD) rely on animals exposed to stress early in life (neonatal maternal separation, NMS) or in adulthood (restraint stress, RS). PURPOSE Since many clinical cases of FD have been associated with stress in early life followed by stress in adulthood, a sequential model simulating the clinical situation is described. To explore the validity of the model, the efficacy of STW5, a multicomponent herbal preparation of proven usefulness in FD, was tested. STUDY DESIGN/METHODS A sequential stress model established where rats are exposed to NMS after birth followed later by RS in adulthood. Stress hormones and ghrelin were measured in plasma, while responsiveness of stomach fundus strips to smooth muscle stimulants and relaxants was assessed ex-vivo. The effectiveness of treatment with STW5 a few days before and during exposure to RS in preventing changes induced by the stress model is reported and compared to its efficacy when used in animals subjected to RS alone. RESULTS Responses to both stimulants and relaxants were reduced to various extents in the studied models, but treatment with STW5 tended to normalize gastric responsiveness. Plasma levels of ghrelin, corticosterone releasing factor, and corticosterone were raised by RS as well as the sequential model. Treatment with STW5 tended to prevent the deranged parameters. CONCLUSION The sequential stress model has a place in drug screening for potential usefulness in FD as it simulates more the clinical setting. Furthermore, the findings shed more light on the mechanisms of action of STW5 in FD.
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Affiliation(s)
- Heba Abdel-Aziz
- Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany; Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
| | - Walaa Wadie
- Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Hala F Zaki
- Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Jürgen Müller
- Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Olaf Kelber
- Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
| | - Mohamed T Khayyal
- Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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Intestinal barrier function and the brain-gut axis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2014; 817:73-113. [PMID: 24997030 DOI: 10.1007/978-1-4939-0897-4_4] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The luminal-mucosal interface of the intestinal tract is the first relevant location where microorganism-derived antigens and all other potentially immunogenic particles face the scrutiny of the powerful mammalian immune system. Upon regular functioning conditions, the intestinal barrier is able to effectively prevent most environmental and external antigens to interact openly with the numerous and versatile elements that compose the mucosal-associated immune system. This evolutionary super system is capable of processing an astonishing amount of antigens and non-immunogenic particles, approximately 100 tons in one individual lifetime, only considering food-derived components. Most important, to develop oral tolerance and proper active immune responses needed to prevent disease and inflammation, this giant immunogenic load has to be managed in a way that physiological inflammatory balance is constantly preserved. Adequate functioning of the intestinal barrier involves local and distant regulatory networks integrating the so-called brain-gut axis. Along this complex axis both brain and gut structures participate in the processing and execution of response signals to external and internal changes coming from the digestive tract, using multidirectional pathways to communicate. Dysfunction of brain-gut axis facilitates malfunctioning of the intestinal barrier, and vice versa, increasing the risk of uncontrolled immunological reactions that may trigger mucosal and brain low-grade inflammation, a putative first step to the initiation of more permanent gut disorders. In this chapter, we describe the structure, function and interactions of intestinal barrier, microbiota and brain-gut axis in both healthy and pathological conditions.
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Abstract
INTRODUCTION While delayed emptying is the defining criterion for gastroparesis, prokinetics often only have a limited impact on symptoms and have been associated with potentially serious adverse effects. The goal of this study was to determine how this information and regulatory changes affected gastroparesis management. METHODS The electronic medical records of patients seen between 2003 and 2012 in the outpatient clinic of a large tertiary center were retrieved based on the billing diagnosis of gastroparesis. Demographic, clinical, and survival data were abstracted. RESULTS A total of 709 patients were identified, with diabetes (21.2 %) and prior surgery (9.8 %) being the most common identifiable causes. The majority of patients (56 %) had idiopathic gastroparesis. The cohort was female predominant (79.5 %) with an average age of 45.4 ± 0.6 years. At the index encounter, 61.8 % received prokinetics. About one-third (37.7 %) used antiemetics at least intermittently. Between 2003 and 2012, prokinetic use dropped from 81 to 43 %, while the use of antiemetics increased from 14 to 41 %. Similarly, there was a significant increase in prescribed opioids and antidepressants. During the period of the study, 44 patients (6.2 %) died. Increasing age, a higher comorbidity burden, anxiety, and medication use were associated with higher mortality risks. CONCLUSION This large outpatient cohort suggests that treatment trends move away from prokinetics and focus on symptom-oriented therapy and/or confounding mood disorders.
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From ischochymia to gastroparesis: proposed mechanisms and preferred management of dyspepsia over the centuries. Dig Dis Sci 2014; 59:1088-98. [PMID: 24715546 DOI: 10.1007/s10620-014-3144-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Accepted: 03/26/2014] [Indexed: 12/12/2022]
Abstract
Dyspeptic symptoms are common with most patients suffering functional disorders that remain a therapeutic challenge for medical practitioners. Within the last three decades, gastric infection, altered motility, and hypersensitivity have gained and lost traction in explaining the development of functional dyspepsia. Considering these shifts, the aim of this review was to analyze changing understanding of and approaches to dyspepsia over a longer time period. Monographs, textbooks, and articles published during the last three centuries show that our understanding of normal gastric function has improved dramatically. With increased insight came new ideas about disease mechanisms, diagnostic options, and treatments. Despite shifts over time, the importance of functional abnormalities was recognized early on and explained in the context of societal influences and stressors, anxieties, and biological influences, thus resembling the contemporary biopsychosocial model of illness. Symptoms were often attributed to changes in secretion, motility, and sensation or perception with technological innovation often influencing proposed mechanisms and treatments. Many of the principles or even agents applied more than a century ago are still part of today's approach. This includes acid suppression, antiemetics, analgesics, and even non-pharmacologic therapies, such as gastric decompression or electrical stimulation of the stomach. This historical information does not only help us understand how we arrived at our current state of knowledge and standards of care, it also demonstrates that enthusiastic adoption of various competing explanatory models and the resulting treatments often did not survive the test of time. In view of the benign prognosis of dyspepsia, the data may function as a call for caution to avoid the potential harm of overly aggressive approaches or treatments with a high likelihood of adverse effects.
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Jones MP, Coppens E, Vos R, Holvoet L, Luyten P, Tack J, Van Oudenhove L. A multidimensional model of psychobiological interactions in functional dyspepsia: a structural equation modelling approach. Gut 2013; 62:1573-80. [PMID: 22917658 DOI: 10.1136/gutjnl-2012-302634] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Gastric sensorimotor function, abuse history, 'trait' and 'state' psychological factors and 'somatisation' all play a role in functional dyspepsia (FD) and its associated impaired quality of life (QoL), but their interplay remains poorly understood. We aimed to test a comprehensive, a priori hypothesised model of interactions between these dimensions in FD. DESIGN In 259 FD patients, we studied gastric sensitivity with a barostat. We measured abuse history (sexual/physical, childhood/adulthood), 'trait' (alexithymia, trait anxiety) and 'state' (positive/negative affect, depression, panic disorder) psychological factors, somatic symptom reporting (somatic symptom count, dyspepsia, irritable bowel syndrome and fatigue symptoms) and QoL (physical, mental) using validated questionnaires. Confirmatory factor analysis (CFA) was used to assess whether four a priori hypothesised latent variables ('abuse', 'trait affectivity', 'state affect' and 'somatic symptom reporting') were adequately supported by the data. Structural equation modelling (SEM) was used to test the a priori hypothesised relationships between these latent variables and the observed variables gastric sensitivity and QoL. RESULTS Both the CFA and SEM models fitted the data adequately. Abuse exerted its effect directly on 'somatic symptom reporting', rather than indirectly through psychological factors. A reciprocal relationship between 'somatic symptom reporting' and 'state affect' was found. Gastric sensitivity influences 'somatic symptom reporting' but not vice versa. 'Somatic symptom reporting' and 'trait affectivity' are the main determinants of physical and mental QoL, respectively. CONCLUSIONS We present the first comprehensive model elucidating the complex interactions between multiple dimensions (gastric sensitivity, abuse history, 'state' and 'trait' psychological factors, somatic symptom reporting and QoL) in FD.
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Affiliation(s)
- Michael P Jones
- Department of Psychology, Macquarie University, Sydney, Australia
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Adding to the burden: gastrointestinal symptoms and syndromes in multiple sclerosis. Mult Scler Int 2013; 2013:319201. [PMID: 24163768 PMCID: PMC3791579 DOI: 10.1155/2013/319201] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 08/14/2013] [Indexed: 02/06/2023] Open
Abstract
Background. Multiple sclerosis (MS) patients often suffer from gastrointestinal (GI) symptoms. However, the full extent and prevalence of such symptoms are not clearly established. Thus, we sought to define the prevalence of GI symptoms and syndromes in those with MS. Methods. 218 MS patients completed self-reported demographic and clinical data questionnaires as well as several standardized surveys probing MS severity and GI health. Results. Nearly two thirds (65.6%) of patients endorsed at least one persistent GI symptom. Constipation (36.6%), dysphagia (21.1%), and fecal incontinence (15.1%) were common. Surprisingly, nearly 30% (28.4%) of the patients reported dyspeptic symptoms. Using validated diagnostic algorithms, patients met criteria for functional dysphagia (14.7%), functional dyspepsia (16.5%), functional constipation (31.7%), and IBS (19.3%), among others. Functional dysphagia, functional dyspepsia, and IBS were significantly more common in those with self-identified mood disorders. Conclusions. Constipation, fecal incontinence, and dysphagia are indeed frequent symptoms seen in MS patients. We also noted a ~30% prevalence of dyspepsia in this population. The mechanisms driving this association are not clear and require further study. However, due to this high prevalence, dyspeptic symptoms should be incorporated into the routine assessment of MS patients and, if found, may warrant collaborative referral with a GI specialist.
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Abstract
BACKGROUND AND OBJECTIVES A history of sexual abuse is to be found in approximately 40% of all adult patients with gastrointestinal complaints. Data on the prevalence of child sexual abuse (CSA) in children with chronic abdominal pain (CAP) are lacking. The objective of this systematic review is to determine the prevalence of CSA in pediatric patients with CAP. METHODS We conducted a systematic literature search in the electronic databases MEDLINE, EMBASE, PsychInfo, and ERIC. Reference lists of relevant articles were scanned for additional citations. We selected case-control, cohort and cross-sectional studies investigating the prevalence of CSA in children with CAP, ages 0 to 18 years. Data were extracted from relevant studies, which were assessed for methodological quality by 2 independent reviewers. Prevalence of CSA was the main outcome measure. RESULTS The literature search yielded a total of 269 articles. Only 2 studies met our inclusion criteria, reporting CSA in 2.1% and 8.0% of children (age range 4-21 years) with CAP. Both studies were conducted in small groups (n = 48 and n = 50) without control group(s) and did not use standardized or validated instruments for diagnosing CSA. CONCLUSIONS According to existing data, the prevalence of a history of CSA in pediatric patients with CAP is lower than in adult patients; however, no well-designed studies have been conducted in children. Future research is required to determine a reliable prevalence of CSA in children with CAP.
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Abstract
In this Review, after a brief historical introduction, we first provide an overview of epidemiological studies that demonstrate an association between functional dyspepsia and psychological traits, states or psychiatric disorders. These studies suggest an important intrinsic role for psychosocial factors and psychiatric disorders, especially anxiety and depression, in the aetiopathogenesis of functional dyspepsia, in addition to their putative influence on health-care-seeking behaviour. Second, we describe pathophysiological evidence on how psychosocial factors and psychiatric disorders might exert their role in functional dyspepsia. Novel insights from functional brain imaging studies regarding the integration of gut-brain signals, processed in homeostatic-interoceptive brain regions, with input from the exteroceptive system, the reward system and affective and cognitive circuits, help to clarify the important role of psychological processes and psychiatric morbidity. We therefore propose an integrated model of functional dyspepsia as a disorder of gut-brain signalling, supporting a biopsychosocial approach to the diagnosis and management of this disorder.
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De Giorgi F, Sarnelli G, Cirillo C, Savino IG, Turco F, Nardone G, Rocco A, Cuomo R. Increased severity of dyspeptic symptoms related to mental stress is associated with sympathetic hyperactivity and enhanced endocrine response in patients with postprandial distress syndrome. Neurogastroenterol Motil 2013; 25:31-8.e2-3. [PMID: 22908903 DOI: 10.1111/nmo.12004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Mental stress (MS) may alter gastric sensory-motor function. The aim of the study was to assess postprandial autonomic nervous system activity and stress hormones in response to acute mental stress in dyspeptic patients. METHODS A total of 25 patients with postprandial distress syndrome (PDS; 11 mol L(-1), age 35.9 ± 9.3 years) and 12 healthy controls (5 mol L(-1), age 25.8 ± 4.6 years) underwent electrogastrography and (13) C-octanoate gastric emptying study using a 480 kcal solid meal. Heart rate variability (LF/HF ratio) and corticotrophin-releasing factor, adrenocorticotropic hormone (ACTH), and cortisol serum levels were also evaluated. Dyspeptic symptoms were scored by analogue visual scale and expressed as symptoms total score (TS). The protocol was repeated twice in each subject, with and without a mental stress test before the meal. KEY RESULTS Mental stress significantly increased postprandial symptoms severity in patients (TS: stress 111 ± 18 vs basal 50 ± 10; P < 0.05). Low-/high-frequency component ratio was significantly higher in patients after MS at 120 min (stress 5.46 ± 0.41 vs basal 3.41 ± 0.64; P < 0.01) and 180 min (stress 5.29 ± 0.2 vs basal 3.58 ± 0.19; P < 0.05). During stress session, in patients we found a significantly higher ACTH level than baseline at 30, 60, 90, 150, 210, 240, and 270 min and a significantly higher cortisol level at 30, 60, 90, 120, 210, and 270 min. Gastric emptying rate and electrical activity were not influenced by MS. CONCLUSIONS & INFERENCES In PDS patients, administration of MS before meal increases symptoms severity by inducing sympathetic hyperactivity and increased stress hormones levels. As the gastric emptying looks not altered, we conclude that these neurohormonal responses mainly affect sensitive function.
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Affiliation(s)
- F De Giorgi
- Department of Clinical and Experimental Medicine, University of Naples Federico II, Naples, Italy
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Koloski NA, Jones M, Talley NJ. Commentary: Psychological disorders linked to functional dyspepsia. Aliment Pharmacol Ther 2012; 36:1099-100; discussion 1100-1. [PMID: 23130770 DOI: 10.1111/apt.12079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- N A Koloski
- Faculty of Health, University of Newcastle, Callaghan, NSW, Australia.
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Guo WJ, Zhang YL, Yao SK, Yin LJ, Yan J, Li HL. Relationship between symptoms and proximal stomach function in patients with functional dyspepsia. Shijie Huaren Xiaohua Zazhi 2012; 20:1623-1629. [DOI: 10.11569/wcjd.v20.i18.1623] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prevalence of impaired proximal stomach function and its relationship to symptoms in patients with functional dyspepsia (FD).
METHODS: Fifty-nine patients with FD and 32 healthy subjects (HS) were enrolled in this study. After an overnight fast of at least 12 h, a double-lumen polyvinyl tube with an adherent plastic bag that was finely folded was introduced through the patient's mouth. A gastric barostat was used to evaluate proximal stomach function (sensitivity, accommodation and compliance). After an overnight fast, gastric emptying was measured by single photon emission computerized tomography (SPECT). The gastric emptying curve was plotted to calculate the gastric emptying half-time. Individual dyspepsia symptom scores were obtained for all patients and their relationship with proximal stomach function was assessed. Logistic regression analysis and χ2 statistics were used to identify the association between proximal stomach function and symptoms.
RESULTS: Visceral hypersensitivity to gastric distention was found in 44.07% of the patients, and their gastric emptying half-time did not significantly differ from that of patients with normal sensitivity. Epigastric pain was significantly more prevalent in patients with visceral hypersensitivity than in those with normal sensitivity (P < 0.01). Epigastric pain was independently and significantly associated with hypersensitivity to gastric distention (OR = 4.430, P < 0.05). Impaired gastric accommodation was found in 37.29% of the patients, and their gastric emptying half-time did not differ from that of other patients. Impaired gastric accommodation to gastric distention was associated with a higher prevalence of early satiety (P < 0.05). The presence of early satiety was the only symptom that was independently associated with impaired accommodation to gastric distention (OR = 3.231, P < 0.05). Reduced compliance was found in 54.24% of the patients; however, no relationship was found between reduced compliance and dyspeptic symptoms.
CONCLUSION: Symptoms are associated with impaired proximal stomach function in patients with FD. Epigastric pain and early satiety can be used to predict the presence of hypersensitivity and impaired accommodation, respectively.
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