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Xu W, Qiu Y, Qiu H, Zhong M, Li L. Serum ACTH and Cortisol Level is Associated with the Acute Gastrointestinal Injury Grade in ICU Patients. Int J Gen Med 2024; 17:127-134. [PMID: 38249620 PMCID: PMC10799574 DOI: 10.2147/ijgm.s445741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 01/11/2024] [Indexed: 01/23/2024] Open
Abstract
Background The relationship between acute gastrointestinal symptoms and cortisol or adrenocorticotropic hormone (ACTH) levels has rarely been reported. We hypothesized that the elevation of serum cortisol or ACTH levels may be correlated with the severity of the acute gastrointestinal injury grade (AGI). Methods This study was an observational study. All patients were admitted to the ICU between 2019.1.1 and 2020.1.1.. Serum ACTH and cortisol levels and clinical data were collected from the electronic medication records. The highest AGI grade during the ICU stay was the major endpoint to observe. The patient was treated in a standard procedure in the ICU. Results A total of 235 patients were included in our study, 132 of whom developed AGI. In univariate regression, cortisol level was found to be a risk factor for 28-day mortality. Serum cortisol and ACTH levels correlated with APACHE II, AGI grade, PCT, and CRP levels. Spearman analysis and partial correlation analysis indicated that cortisol and ACTH levels were correlated with AGI grade. Conclusion The ACTH and cortisol levels were positively correlated with the higher severity of AGI grade. The cortisol level may be a useful way to access the GI injury.
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Affiliation(s)
- Wen Xu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Yuzhen Qiu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Hongping Qiu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Ming Zhong
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Lei Li
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
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Al-Kuraishy HM, Al-Gareeb AI, Zaidalkiani AT, Alexiou A, Papadakis M, Bahaa MM, Al-Faraga A, Batiha GES. Calprotectin in Parkinsonian disease: Anticipation and dedication. Ageing Res Rev 2024; 93:102143. [PMID: 38008403 DOI: 10.1016/j.arr.2023.102143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/13/2023] [Accepted: 11/22/2023] [Indexed: 11/28/2023]
Abstract
Parkinson's disease (PD) is a neurodegenerative disease due to degeneration of dopaminergic neurons (DNs) in the substantia nigra pars compacta (SNpc). PD is characterized by motor and non-motor symptoms. Non-motor symptoms such as constipation and dysfunction of gastrointestinal tract (GIT) motility together with medications used in the management of PD affect gut microbiota. Alterations of gut microbiota with development of gut dyspiosis can induce momentous changes in gut barrier with subsequent systemic inflammation and induction of neuroinflammation. It has been shown that calprotectin which reflect intestinal inflammation and gut barrier injury are augmented in PD. Therefore, this review aims to elucidate the possible role of gut barrier injury and associated dysbiois in PD neuropathology, and how calprotectin reflects gut barrier injury in PD. Benefit of this review was to elucidate that high fecal calprotectin level in PD patients indicated gut dysbiosis and intestinal inflammation. Early increment of fecal calprotectin indicates the development of gut dysbiosis and/or gut-barrier injury which may precede motor symptoms by decades. Thus, fecal calprotectin could be a diagnostic and prognostic biomarker in PD. preclinical and clinical studies are warranted in this regard to emphasize the potential role of fecal calprotectin in PD neuropathology.
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Affiliation(s)
- Hayder M Al-Kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Ali I Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Ayah Talal Zaidalkiani
- Department of Nutrition, Faculty of Pharmacy and Medical Sciences, University of Petra, 11196 Amman, Jordan
| | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia; AFNP Med, 1030 Wien, Austria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283 Wuppertal, Germany
| | - Mostafa M Bahaa
- Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt.
| | - Ammar Al-Faraga
- Department of Biochemistry, College of Science University of Jeddah, Saudi Arabia
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira 22511, Egypt
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Understanding the Connection between Gut Homeostasis and Psychological Stress. J Nutr 2023; 153:924-939. [PMID: 36806451 DOI: 10.1016/j.tjnut.2023.01.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 12/24/2022] [Accepted: 01/17/2023] [Indexed: 02/03/2023] Open
Abstract
Long-term exposure to adverse life events that provoke acute or chronic psychological stress (hereinafter "stress") can negatively affect physical health and even increase susceptibility to psychological illnesses, such as anxiety and depression. As a part of the hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor (CRF) released from the hypothalamus is primarily responsible for the stress response. Typically, CRF disrupts the gastrointestinal system and leads to gut microbiota dysbiosis, thereby increasing risk of functional gastrointestinal diseases, such as irritable bowel syndrome. Furthermore, CRF increases oxidative damage to the colon and triggers immune responses involving mast cells, neutrophils, and monocytes. CRF even affects the differentiation of intestinal stem cells (ISCs), causing enterochromaffin cells to secrete excessive amounts of 5-hydroxytryptamine (5-HT). Therefore, stress is often accompanied by damage to the intestinal epithelial barrier function, followed by increased intestinal permeability and bacterial translocation. There are multi-network interactions between the gut microbiota and stress, and gut microbiota may relieve the effects of stress on the body. Dietary intake of probiotics can provide energy for ISCs through glycolysis, thereby alleviating the disruption to homeostasis caused by stress, and it significantly bolsters the intestinal barrier, alleviates intestinal inflammation, and maintains endocrine homeostasis. Gut microbiota also directly affect the synthesis of hormones and neurotransmitters, such as CRF, 5-HT, dopamine, and norepinephrine. Moreover, the Mediterranean diet enhances the stress resistance to some extent by regulating the intestinal flora. This article reviews recent research on how stress damages the gut and microbiota, how the gut microbiota can improve gut health by modulating injury due to stress, and how the diet relieves stress injury by interfering with intestinal microflora. This review gives insight into the potential role of the gut and its microbiota in relieving the effects of stress via the gut-brain axis.
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Im EO, Kim G, Choi M, Chee W. Gastrointestinal symptoms in four major racial/ethnic groups of midlife women: race/ethnicity and menopausal status. Menopause 2021; 29:156-163. [PMID: 34873105 PMCID: PMC8795485 DOI: 10.1097/gme.0000000000001898] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE The purpose of this study was to explore the associations of race/ethnicity and menopausal status to gastrointestinal (GI) symptoms experienced during the menopausal transition while considering multiple factors that could influence the symptoms. METHODS This secondary analysis was conducted with the data from 1,051 women from 2 Internet-based studies on midlife women's health issues. In the original studies, the data were collected using a dozen questions on sociodemographic and health/menopausal factors and the GI Index for Midlife Women. The data were analyzed utilizing ANOVA, multiple logistic regression, and hierarchical linear regression analyses. RESULTS When covariates were controlled, being Non-Hispanic (N-H) Asian was a significant factor that influenced the total numbers of GI symptoms (β = -0.26) and total severity scores of GI symptoms (β = -0.26). When covariates were controlled, premenopausal status was the strongest factor that influenced the total numbers of GI symptoms in all participants, Hispanics, N-H Whites, N-H African Americans, and N-H Asians (β = 53, -0.40, -0.77, -0.76, -0.26, respectively) and the total severity scores of GI symptoms in all participants, Hispanics, N-H Whites, N-H African Americans, and N-H Asians (β = -0.50, -0.38, -0.72, -0.75, -0.25, respectively). CONCLUSIONS This study supports the association of race/ethnicity and menopausal status to GI symptoms experienced during the menopausal transition.
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Affiliation(s)
- Eun-Ok Im
- School of Nursing, Emory University, Atlanta, GA
| | - Gayeong Kim
- School of Nursing, Emory University, Atlanta, GA
| | - Miyoung Choi
- School of Nursing, Emory University, Atlanta, GA
- Department of Nursing, Chungbuk National University
| | - Wonshik Chee
- School of Nursing, Emory University, Atlanta, GA
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Pagoldh J, Lundgren D, Suhr OB, Karling P. Irritable bowel syndrome-like symptoms in treated microscopic colitis patients compared with controls: a cross-sectional study. Gastroenterol Rep (Oxf) 2020; 8:374-380. [PMID: 33163193 PMCID: PMC7603863 DOI: 10.1093/gastro/goz069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 08/04/2019] [Accepted: 11/30/2019] [Indexed: 12/12/2022] Open
Abstract
Background The prevalence of irritable bowel syndrome (IBS)-like symptoms is high in untreated patients with microscopic colitis (MC), but there is uncertainty of the prevalence of IBS-like symptoms in treated patients. We assessed the degree of IBS-like symptoms in patients with MC in comparison to control subjects, and investigated the association between IBS-like symptoms and faecal calprotectin (FC) in MC patients. Methods Patients with an established MC diagnosis (n = 57) were compared to sex- and age-matched controls (n = 138) for scores in the GSRS-IBS (Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome) and HADS (Hospital Anxiety Depression Scale). In MC patients, an FC level was simultaneously analysed. Results The median interval from MC diagnoses to the time the subjects participated in the study was 5.5 years (25th–75th percentiles; 4.5–9.5 years). The total GSRS-IBS score, subscores for abdominal pain, bloating, and diarrhoea were significantly higher in MC patients compared to controls (all P < 0.001). There was a significant correlation between FC levels and reported bowel frequency (P = 0.023), but there was no correlation between FC levels and GSRS-IBS scores. Patients with MC had significantly higher scores on anxiety (HADS-A) (P < 0.001) and used more selective serotonin-reuptake-inhibitor drugs (P = 0.016) than the control subjects. However, only the control subjects (not the patients with MC) showed significant correlations between GSRS-IBS scores and HADS scores. Conclusions Patients with MC reported more IBS-like symptoms and anxiety than control subjects but neither FC levels nor symptoms of affectivity were significantly correlated with IBS-like symptoms.
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Affiliation(s)
- Jenny Pagoldh
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - David Lundgren
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Ole B Suhr
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Pontus Karling
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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Wong HLX, Qin HY, Tsang SW, Zuo X, Che S, Chow CFW, Li X, Xiao HT, Zhao L, Huang T, Lin CY, Kwan HY, Yang T, Longo FM, Lyu A, Bian ZX. Early life stress disrupts intestinal homeostasis via NGF-TrkA signaling. Nat Commun 2019; 10:1745. [PMID: 30988299 PMCID: PMC6465335 DOI: 10.1038/s41467-019-09744-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 03/28/2019] [Indexed: 12/29/2022] Open
Abstract
Early childhood is a critical period for development, and early life stress may increase the risk of gastrointestinal diseases including irritable bowel syndrome (IBS). In rodents, neonatal maternal separation (NMS) induces bowel dysfunctions that resemble IBS. However, the underlying mechanisms remain unclear. Here we show that NMS induces expansion of intestinal stem cells (ISCs) and their differentiation toward secretory lineages including enterochromaffin (EC) and Paneth cells, leading to EC hyperplasia, increased serotonin production, and visceral hyperalgesia. This is reversed by inhibition of nerve growth factor (NGF)-mediated tropomyosin receptor kinase A (TrkA) signalling, and treatment with NGF recapitulates the intestinal phenotype of NMS mice in vivo and in mouse intestinal organoids in vitro. Mechanistically, NGF transactivates Wnt/β-catenin signalling. NGF and serotonin are positively correlated in the sera of diarrhea-predominant IBS patients. Together, our findings provide mechanistic insights into early life stress-induced intestinal changes that may translate into treatments for gastrointestinal diseases.
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Affiliation(s)
- Hoi Leong Xavier Wong
- Institute of Brain and Gut Axis (IBAG), Centre of Clinical Research for Chinese Medicine, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Hong-Yan Qin
- Department of Pharmacy, First Hospital of Lanzhou University, 730000, Lanzhou, China
| | - Siu Wai Tsang
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Xiao Zuo
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Sijia Che
- Institute of Brain and Gut Axis (IBAG), Centre of Clinical Research for Chinese Medicine, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Chi Fung Willis Chow
- Institute of Brain and Gut Axis (IBAG), Centre of Clinical Research for Chinese Medicine, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Xi Li
- Department of Gastroenterology, Peking University Shenzhen Hospital, 518035, Shenzhen, China
| | - Hai-Tao Xiao
- School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, 518060, Shenzhen, China
| | - Ling Zhao
- Institute of Brain and Gut Axis (IBAG), Centre of Clinical Research for Chinese Medicine, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Tao Huang
- Institute of Brain and Gut Axis (IBAG), Centre of Clinical Research for Chinese Medicine, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Cheng Yuan Lin
- Institute of Brain and Gut Axis (IBAG), Centre of Clinical Research for Chinese Medicine, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Hiu Yee Kwan
- Institute of Brain and Gut Axis (IBAG), Centre of Clinical Research for Chinese Medicine, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Tao Yang
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Frank M Longo
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Aiping Lyu
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Zhao-Xiang Bian
- Institute of Brain and Gut Axis (IBAG), Centre of Clinical Research for Chinese Medicine, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.
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Lundgren D, Rutegård J, Eklöf V, Palmqvist R, Karling P. Patients with longstanding ulcerative colitis in remission do not have more irritable bowel syndrome-like symptoms than controls. BMC Gastroenterol 2016; 16:139. [PMID: 27881072 PMCID: PMC5121960 DOI: 10.1186/s12876-016-0553-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 11/17/2016] [Indexed: 12/14/2022] Open
Abstract
Background Irritable bowel syndrome (IBS) is more common in patients with ulcerative colitis (UC) than expected. The prevalence of IBS in patients with UC with longstanding disease is not known. We investigated the prevalence of IBS-like symptoms in patients with UC in remission and longstanding disease in comparison to control subjects. Methods Sixty-eight patients with UC and 33 patients with hereditary familiar colon cancer and who underwent colonoscopy surveillance were included. Faecal calprotectin (FC), Gastrointestinal Symptoms Rating Scale-Irritable Bowel Syndrome (GSRS-IBS) and Hospital Anxiety and Depression scale were fulfilled prior to endoscopy. UC in remission was define by steroid-free clinical remission, a Mayo Score ≤ 1 on endoscopy, a FC ≤ 200 μg/g and no significant active inflammation on colon biopsies. Results Fifty-five UC patients met the criteria for being in remission. The median disease duration was 17 years. The patients with UC in remission tended to have lower scores on total GSRS-IBS score (6 vs 10.5; p = 0.062) and lower or equal scores on all specific IBS symptoms in comparison to controls. There was a moderate but significant correlation between diarrhoea scores and FC levels (in the span ≤ 200 μg/g) (rs 0.38; p = 0.004) in the UC in remission group. Conclusion Patients with UC with longstanding disease and in remission do not have more IBS symptoms than controls. In UC patients in remission the FC level in the lower span showed a moderate correlation to symptoms of diarrhoea. Electronic supplementary material The online version of this article (doi:10.1186/s12876-016-0553-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- D Lundgren
- Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, SE-90187, Umeå, Sweden.
| | - J Rutegård
- Department of Surgery and Perioperative Science, Surgery, Umeå University, SE-90187, Umeå, Sweden
| | - V Eklöf
- Department of Medical Biosciences, Pathology, Umeå University, SE-90187, Umeå, Sweden
| | - R Palmqvist
- Department of Medical Biosciences, Pathology, Umeå University, SE-90187, Umeå, Sweden
| | - P Karling
- Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, SE-90187, Umeå, Sweden
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Karling P, Maripuu M, Wikgren M, Adolfsson R, Norrback KF. Association between gastrointestinal symptoms and affectivity in patients with bipolar disorder. World J Gastroenterol 2016; 22:8540-8548. [PMID: 27784966 PMCID: PMC5064035 DOI: 10.3748/wjg.v22.i38.8540] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Revised: 08/24/2016] [Accepted: 09/12/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To study if anxiety, depression and experience of stress are associated with gastrointestinal (GI) symptoms in patients with bipolar disorder.
METHODS A total of 136 patients with bipolar disorder (mean age 49.9 years; 61% women) and 136 controls from the general population (mean age 51.0 years; 60% women) were included in the study. GI symptoms were assessed with The Gastrointestinal Symptom Rating Scale-irritable bowel syndrome (GSRS-IBS), level of anxiety and depression with The Hospital Anxiety and Depression Scale (HADS) and stress-proneness with Perceived Stress Questionnaire. Over a ten year period, all visits in primary care were retrospectively recorded in order to identify functional GI disorders.
RESULTS In subjects with low total HADS-score, there were no significant differences in GI-symptoms between patients and controls (GSRS-IBS 7.0 vs 6.5, P = 0.513). In the patients with bipolar disorder there were significant correlations between all GSRS and HADS subscores for all symptom clusters except for “constipation” and “reflux”. Factors associated to GI symptoms in the patient group were female sex (adjusted OR = 2.37, 95%CI: 1.07-5.24) and high HADS-Depression score (adjusted OR = 3.64, 95%CI: 1.07-12.4). These patients had also significantly more visits for IBS than patients with low HADS-Depression scores (29% vs 8%, P = 0.008). However, there was no significant differences in consulting behaviour for functional GI disorders between patients and controls (25% vs 17%, P = 0.108).
CONCLUSION Female patients and patients with high HADS depression score reported significantly more GI symptoms, whereas patients with low HADS scores did not differ from control subjects.
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Videlock EJ, Shih W, Adeyemo M, Mahurkar-Joshi S, Presson AP, Polytarchou C, Alberto M, Iliopoulos D, Mayer EA, Chang L. The effect of sex and irritable bowel syndrome on HPA axis response and peripheral glucocorticoid receptor expression. Psychoneuroendocrinology 2016; 69:67-76. [PMID: 27038676 PMCID: PMC4977028 DOI: 10.1016/j.psyneuen.2016.03.016] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2015] [Revised: 03/21/2016] [Accepted: 03/21/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in irritable bowel syndrome (IBS). Enhanced HPA axis response has been associated with reduced glucocorticoid receptor (GR) mediated negative feedback inhibition. We aimed to study the effects of IBS status, sex, or presence of early adverse life events (EAL) on the cortisol response to corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH), and on GR mRNA expression in peripheral blood mononuclear cells (PBMCs). METHODS Rome III+ IBS patients and healthy controls underwent CRF (1μg/kg ovine) and ACTH (250μg) stimulation tests with serial plasma ACTH and cortisol levels measured (n=116). GR mRNA levels were measured using quantitative PCR (n=143). Area under the curve (AUC) and linear mixed effects models were used to compare ACTH and cortisol response measured across time between groups. RESULTS There were divergent effects of IBS on the cortisol response to ACTH by sex. In men, IBS was associated with an increased AUC (p=0.009), but in women AUC was blunted in IBS (p=0.006). Men also had reduced GR mRNA expression (p=0.007). Cumulative exposure to EALs was associated with an increased HPA response. Lower GR mRNA was associated with increased pituitary HPA response and increased severity of overall symptoms and abdominal pain in IBS. CONCLUSION This study highlights the importance of considering sex in studies of IBS and the stress response in general. Our findings also provide support for PBMC GR mRNA expression as a peripheral marker of central HPA response.
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Affiliation(s)
- Elizabeth J. Videlock
- Oppenheimer Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, CA 90095-7378, United States
| | - Wendy Shih
- Department of Biostatistics David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, CA 90095-7378, United States.
| | - Mopelola Adeyemo
- Oppenheimer Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, CA 90095-7378, United States.
| | - Swapna Mahurkar-Joshi
- Oppenheimer Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, CA 90095-7378, United States.
| | - Angela P. Presson
- Division of Epidemiology, Department of Internal Medicine, University of Utah, 295 Chipeta Way, Salt Lake City, UT 84132, United States
| | - Christos Polytarchou
- Oppenheimer Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, CA 90095-7378, United States.
| | - Melissa Alberto
- Oppenheimer Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, CA 90095-7378, United States.
| | - Dimitrios Iliopoulos
- Oppenheimer Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, CA 90095-7378, United States.
| | - Emeran A. Mayer
- Oppenheimer Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, CA 90095-7378, United States
| | - Lin Chang
- Oppenheimer Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, CA 90095-7378, United States.
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Liu HR, Fang XY, Wu HG, Wu LY, Li J, Weng ZJ, Guo XX, Li YG. Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity. World J Gastroenterol 2015; 21:7181-7190. [PMID: 26109804 PMCID: PMC4476879 DOI: 10.3748/wjg.v21.i23.7181] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Revised: 02/26/2015] [Accepted: 04/17/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity.
METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7th week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus.
RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH mRNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats (P < 0.01). CRH mRNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees (P > 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG (P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats (P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced (P < 0.01), but there was no significant change in S-EA rats (P > 0.05).
CONCLUSION: Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.
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Maripuu M, Wikgren M, Karling P, Adolfsson R, Norrback KF. Relative hypo- and hypercortisolism are both associated with depression and lower quality of life in bipolar disorder: a cross-sectional study. PLoS One 2014; 9:e98682. [PMID: 24932586 PMCID: PMC4059634 DOI: 10.1371/journal.pone.0098682] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Accepted: 05/06/2014] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Depression in unipolar and bipolar disorders is associated with hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity. Also, unipolar disorder has recently been shown to exhibit HPA-axis hypoactivity. We studied for the first time how HPA-axis hypo- and hyperactivity relate to depression and disease burden in bipolar disorder. We were interested in studying hypocortisolism; characterized by increased HPA-axis negative feedback sensitivity and lower basal cortisol levels together with the opposite HPA-axis regulatory pattern of hypercortisolism. METHODS This cross-sectional study includes 145 type 1 and 2 bipolar outpatients and 145 matched controls. A dexamethasone-suppression-test (DST) measures the negative feedback sensitivity and a weight-adjusted very-low-dose DST was employed, which is sensitive in identifying hypocortisolism and hypercortisolism. The 25th and 75th percentiles of control post-DST values were used as cut-offs identifying patients exhibiting relative hypo-, and hypercortisolism. Self-report questionnaires were employed: Beck-Depression-Inventory (BDI), Montgomery-Åsberg-Depression-Rating-Scale (MADRS-S), World-Health-Organization-Quality-of-Life-Assessment-100 and Global-Assessment-of-Functioning. RESULTS Patients exhibiting relative hypocortisolism expectedly exhibited lowered basal cortisol levels (p = 0.046). Patients exhibiting relative hypercortisolism expectedly exhibited elevated basal levels (p<0.001). Patients exhibiting relative hypocortisolism showed 1.9-2.0 (BDI, p = 0.017, MADRS-S, p = 0.37) and 6.0 (p<0.001) times increased frequencies of depression and low overall life quality compared with patients exhibiting mid post-DST values (eucortisolism). Adjusted Odds Ratios (OR:s) for depression ranged from 3.8-4.1 (BDI, p = 0.006, MADRS-S, p = 0.011) and was 23.4 (p<0.001) for life quality. Patients exhibiting relative hypercortisolism showed 1.9-2.4 (BDI, p = 0.017, MADRS-S, p = 0.003) and 4.7 (p<0.001) times higher frequencies of depression and low overall life quality compared with patients exhibiting eucortisolism. Adjusted OR:s for depression ranged from 2.2-2.7 (BDI, p = 0.068, MADRS-S, p = 0.045) and was 6.3 (p = 0.008) for life quality. LIMITATIONS The cross-sectional design and lack of pre-established reference values of the DST employed. CONCLUSIONS Relative hypocortisolism and relative hypercortisolism were associated with depression and lower life quality, providing novel insights into the detrimental role of stress in bipolar disorder.
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Affiliation(s)
- Martin Maripuu
- Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden
- * E-mail:
| | - Mikael Wikgren
- Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden
| | - Pontus Karling
- Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Rolf Adolfsson
- Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden
| | - Karl-Fredrik Norrback
- Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden
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Huerta-Franco MR, Vargas-Luna M, Tienda P, Delgadillo-Holtfort I, Balleza-Ordaz M, Flores-Hernandez C. Effects of occupational stress on the gastrointestinal tract. World J Gastrointest Pathophysiol 2013; 4:108-118. [PMID: 24244879 PMCID: PMC3829457 DOI: 10.4291/wjgp.v4.i4.108] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Revised: 09/12/2013] [Accepted: 10/16/2013] [Indexed: 02/06/2023] Open
Abstract
The aim of this review is to provide a general overview of the relationship between occupational stress and gastrointestinal alterations. The International Labour Organization suggests occupational health includes psychological aspects to achieve mental well-being. However, the definition of health risks for an occupation includes biological, chemical, physical and ergonomic factors but does not address psychological stress or other affective disorders. Nevertheless, multiple investigations have studied occupational stress and its physiological consequences, focusing on specific risk groups and occupations considered stressful. Among the physiological effects of stress, gastrointestinal tract (GIT) alterations are highly prevalent. The relationship between occupational stress and GIT diseases is evident in everyday clinical practice; however, the usual strategy is to attack the effects but not the root of the problem. That is, in clinics, occupational stress is recognized as a source of GIT problems, but employers do not ascribe it enough importance as a risk factor, in general, and for gastrointestinal health, in particular. The identification, stratification, measurement and evaluation of stress and its associated corrective strategies, particularly for occupational stress, are important topics to address in the near future to establish the basis for considering stress as an important risk factor in occupational health.
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13
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Karling P, Danielsson Å, Wikgren M, Söderström I, Del-Favero J, Adolfsson R, Norrback KF. The relationship between the val158met catechol-O-methyltransferase (COMT) polymorphism and irritable bowel syndrome. PLoS One 2011; 6:e18035. [PMID: 21437260 PMCID: PMC3060919 DOI: 10.1371/journal.pone.0018035] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2010] [Accepted: 02/22/2011] [Indexed: 12/18/2022] Open
Abstract
Background The catechol-O-methyltransferase (COMT) enzyme has a key function in the degradation of catecholamines and a functional polymorphism is val158met. The val/val genotype results in a three to fourfold higher enzymatic activity compared with the met/met genotype, with the val/met genotype exhibiting intermediate activity. Since pain syndromes as well as anxiety and depression are associated to low and high COMT activity respectively and these conditions are all associated with irritable bowel syndrome (IBS) we wanted for the first time to explore the relationship between the polymorphism and IBS. Methodology/Principal Findings 867 subjects (445 women) representative of the general population and 70 consecutively sampled patients with IBS (61 women) were genotyped for the val158met polymorphism and the IBS patients filled out the Hospital-Anxiety-and-Depression-Scale (HADS) questionnaire, and an IBS symptom diary. Results There was a significantly higher occurrence of the val/val genotype in patients compared with controls (30% vs 20%; Chi2 (1) 3.98; p = 0.046) and a trend toward a lower occurrence of the val/met genotype in IBS patients compared with controls (39% vs 49%; Chi2 (1) 2.89; p = 0.089). Within the IBS patients the val/val carriers exhibited significantly increased bowel frequency (2.6 vs 1.8 stools per day; Chi2 (1) 5.3; p = 0.03) and a smaller proportion of stools with incomplete defecation (41% vs 68%; Chi2 (1) 4.3; p = 0.04) compared with the rest (val/met+met/met carriers). The val/val carriers also showed a trend for a smaller proportion of hard stools (0% vs 15%; Chi2 (1) 3.2; p = 0.08) and a higher frequency of postprandial defecation (26% vs 21%; Chi2 (1) 3.0; p = 0.08). Conclusions/Significance In this study we found an association between the val/val genotype of the val158met COMT gene and IBS as well as to specific IBS related bowel pattern in IBS patients.
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Affiliation(s)
- Pontus Karling
- Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
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Burr RL, Jarrett ME, Cain KC, Jun SE, Heitkemper MM. Catecholamine and cortisol levels during sleep in women with irritable bowel syndrome. Neurogastroenterol Motil 2009; 21:1148-e97. [PMID: 19573081 PMCID: PMC2820403 DOI: 10.1111/j.1365-2982.2009.01351.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Evidence suggests that patients with irritable bowel syndrome (IBS) are hyper-responsive to environmental, physical and visceral stimuli. IBS patients also frequently report poor sleep quality. This study compared serum cortisol and plasma catecholamine levels during sleep between women with IBS (n = 30) and healthy controls (n = 31), and among subgroups within the IBS sample based on predominant stool patterns, IBS-diarrhoea (n = 14), IBS-constipation (n = 7) and IBS-alternators (n = 9). Cortisol was measured from serial blood samples drawn every 20 min, and catecholamines every hour, in a sleep laboratory from 8 pm until awakening. Because of the varied sleep schedules of the individual participants, each subject's hormone series time base was referenced with respect to their onset of Stage 2 sleep. Overall, there were no significant differences in cortisol or catecholamine patterns between women with IBS and controls, nor were there any group by time interactions. However, women with constipation-predominant IBS demonstrated significantly increased noradrenaline, adrenaline and cortisol levels throughout the sleep interval, and women with diarrhoea-predominant IBS were significantly lower on noradrenaline and cortisol. These results suggest that differences in neuroendocrine levels during sleep among IBS predominant bowel pattern subgroups may be greater than differences between IBS women and controls. Neuroendocrine profiles during sleep may contribute to our understanding of symptom expression in IBS.
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Affiliation(s)
- Robert L. Burr
- Dept. of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA
| | - Monica E. Jarrett
- Dept. of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA
| | - Kevin C. Cain
- Dept. of Biostatistics and Office of Nursing Research, University of Washington, Seattle, WA
| | - Sang-Eun Jun
- Dept. of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA
| | - Margaret M. Heitkemper
- Dept. of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA
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Paschos KA, Kolios G, Chatzaki E. The corticotropin-releasing factor system in inflammatory bowel disease: prospects for new therapeutic approaches. Drug Discov Today 2009; 14:713-20. [PMID: 19379831 DOI: 10.1016/j.drudis.2009.04.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2008] [Revised: 04/01/2009] [Accepted: 04/06/2009] [Indexed: 12/16/2022]
Abstract
Mounting evidence suggests that stress is implicated in the development of inflammatory bowel disease (IBD), via initial nervous disturbance and subsequent immune dysfunction through brain-gut interactions. The corticotropin-releasing factor (CRF) system, being the principal neuroendocrine coordinator of stress responses, is involved in the inflammatory process within the gastrointestinal tract, via vagal and peripheral pathways, as implied by multiple reports reviewed here. Blocking of CRF receptors could theoretically exert beneficial anti-inflammatory effects in colonic tissues. The recently synthesised small-molecule CRF(1) antagonists or alternatively non-peptide CRF(2) antagonists when available, may become new reliable options in the treatment of IBD.
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Affiliation(s)
- Konstantinos A Paschos
- Laboratory of Pharmacology, Faculty of Medicine, Laboratory of Pharmacology, Democritus University of Thrace (DUTH), DUTH, Dragana, Alexandroupolis 68100, Thrace, Greece
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Kim YS, Lee MY, Choi CS, Sohn YW, Park BR, Choi MG, Nah YH, Choi SC. The effect of chronic variable stress on bowel habit and adrenal function in rats. J Gastroenterol Hepatol 2008; 23:1840-6. [PMID: 18752563 DOI: 10.1111/j.1440-1746.2008.05524.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND AIM Increased colonic motility is a well-known stress response and corticotropin releasing hormone plays an important role in this response, but sequential change of bowel habit and adrenal function during chronic stress has not been reported. The objective of this study was to evaluate the effect of chronic stress on bowel habit and adrenal function. METHODS Male Sprague-Dawley rats were exposed to chronic variable stress (CVS) for 6 weeks. We measured daily the number and weight of pellets and weekly urinary corticosterone. After 6 weeks of experiment, visceromotor response (VMR) to colorectal distention (CRD), serum corticosterone and adrenal glands weight were measured. RESULTS The number and weight of pellets in CVS rats was greater than those of the control rats initially and decreased during the later period. However, CVS rats showed continuously exaggerated daily variation of pellet number than control rats to the end of experimental period. Urinary corticosterone was increased in CVS rat until the fifth week, but urine and serum corticosterone were not statistically different between groups at the sixth week. However, the relative weight of adrenal glands was higher in CVS rats at the sixth week. CVS rats showed exaggerated VMR to CRD than the control rats. CONCLUSIONS The prolonged and variable stress to rats induced sustained bowel habit dysfunction and visceral hypersensitivity without adaptation. Chronic stress also increased adrenal activity from the early phase and finally caused adrenal hypertrophy with relatively decreased activity. But adrenal change was not parallel to bowel habit change and it remains to be seen whether adrenal dysfunction is directly related to bowel habit dysfunction.
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Affiliation(s)
- Yong S Kim
- Digestive Disease Research Institute and Gastroenterology, School of Medicine, Wonkwang University, Iksan, Korea
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