Childhood Trauma Is Associated With Hypothalamic-Pituitary-Adrenal Axis Responsiveness in Irritable Bowel Syndrome

Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, California 90095-7378, USA.
Gastroenterology (Impact Factor: 13.93). 09/2009; 137(6):1954-62. DOI: 10.1053/j.gastro.2009.08.058
Source: PubMed

ABSTRACT A history of early adverse life events (EALs) is associated with a poorer outcome and higher levels of distress in adult patients with functional gastrointestinal disorders. An EAL is thought to predispose individuals to develop a range of chronic illnesses by inducing persistent changes in the central stress response systems, including the hypothalamic-pituitary-adrenal (HPA) axis. We sought to determine if EALs affect the HPA axis response to a visceral stressor in irritable bowel syndrome (IBS) patients and healthy controls, and to determine if this is affected by sex or related to symptoms or quality of life.
Forty-four IBS patients (25 women, 19 men) and 39 healthy controls (21 women, 18 men) were assessed for gastrointestinal and psychological symptoms and EALs by validated questionnaires and interview. All subjects underwent a visceral stressor (sigmoidoscopy). Salivary cortisol was collected at baseline and serially for 1 hour poststressor.
Twenty-one IBS patients and 18 controls had EALs. In subjects with and without IBS, an EAL was associated with higher mean (+/-SD) cortisol levels (0.32 +/- 0.2 vs 0.20 +/- 0.1 microg/dL; P = .003) and higher area under the curve (28.1 +/- 17 vs 18.6 +/- 13 microg x min/dL; P = .005) after the stressor compared with subjects without EALs. In IBS, a faster resolution of cortisol to basal values corresponded to lower symptom severity (r = -0.36, P < .05) and better disease-specific quality of life (r = 0.33, P < .05).
HPA axis hyperresponsiveness to a visceral stressor is related more to a history of EALs than to the presence of IBS. However, HPA axis reactivity has a moderating effect on IBS symptoms.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Environmental and genetic factors contribute to variation in irritable bowel syndrome (IBS), anxiety and depression. Comorbidity between these disorders is high. A previous investigation of our population-based twin cohort revealed that low birth weight increased the risk for development of IBS, with environmental influences in utero as the most relevant contributing factor. We hypothesise that both intrauterine and genetic factors influence the co-occurrence of IBS and symptoms of anxiety and depression.MethodsA postal questionnaire sent to 12700 Norwegian twins born between 1967 and 1979 comprised a checklist of 31 illnesses and symptoms, including IBS and symptoms of anxiety and depression. The influence of genetic factors and intrauterine growth on comorbidity between these disorders were analysed in the full sample and compared to those based on only monozygotic (MZ) twin pairs discordant for IBS (95 pairs) in birth weight group¿<¿2500 g and¿¿¿2500 g.ResultsIn the co-twin analyses restricted growth (birth weight¿<¿2500 g) was significantly associated with anxiety and depression (average birth weight difference of 181.0 g (p <0.0001) and 249.9 g (p¿<¿0.0001), respectively).The analysis of the full sample revealed that IBS was significantly associated with symptoms of anxiety (adjusted OR¿=¿2.5, 95% CI: 1.9, 3.3) and depression (adjusted OR¿=¿2.3. 95% CI: 1.8, 3.0). Analyses of MZ pairs discordant for IBS indicated significant associations between IBS and symptoms of anxiety (OR¿=¿3.7, 95% CI: 1.3, 10.5) and between IBS and symptoms of depression (OR¿=¿4.2, 95% CI: 1.7, 9.9) only in the birth weight group below 2500 g.Conclusion Our findings suggest that genetic factors partly explain the association between IBS and symptoms of anxiety and depression. In the low range of birth weight (<2500 g), restricted fetal growth seems to be a common contributing factor to the co-occurrence between these disorders.
    BMC Gastroenterology 02/2015; 15(1):9. DOI:10.1186/s12876-015-0237-y · 2.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Visceral pain is a global term used to describe pain originating from the internal organs, which is distinct from somatic pain. It is a hallmark of functional gastrointestinal disorders such as irritable-bowel syndrome (IBS). Currently, the treatment strategies targeting visceral pain are unsatisfactory, with development of novel therapeutics hindered by a lack of detailed knowledge of the underlying mechanisms. Stress has long been implicated in the pathophysiology of visceral pain in both preclinical and clinical studies. Here, we discuss the complex etiology of visceral pain reviewing our current understanding in the context of the role of stress, gender, gut microbiota alterations, and immune functioning. Furthermore, we review the role of glutamate, GABA, and epigenetic mechanisms as possible therapeutic strategies for the treatment of visceral pain for which there is an unmet medical need. Moreover, we discuss the most widely described rodent models used to model visceral pain in the preclinical setting. The theory behind, and application of, animal models is key for both the understanding of underlying mechanisms and design of future therapeutic interventions. Taken together, it is apparent that stress-induced visceral pain and its psychiatric comorbidities, as typified by IBS, has a multifaceted etiology. Moreover, treatment strategies still lag far behind when compared to other pain modalities. The development of novel, effective, and specific therapeutics for the treatment of visceral pain has never been more pertinent.
    Frontiers in Psychiatry 02/2015; 6. DOI:10.3389/fpsyt.2015.00015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Abnormal processing of visceral sensation at the level of central nervous system has been proven to be important in the pathophysiologic mechanisms of stress related functional gastrointestinal disorders. However, the specific mechanism is still not clear. The insular cortex (IC) was considered as one important visceral sensory area. Moreover, IC has been shown to be involved in various neuropsychiatric diseases such as panic disorders and post-traumatic stress disorder. However, whether IC is important in psychological stress related visceral hypersensitivity has not been studied yet. Aims: In our study, through destructing bilateral IC, we explored whether the IC played a critical role in the formation of visceral hypersensitivity induced by chronic stress on rats. Methods: Chronic partial restraint stress was used to establish viscerally hypersensitive rat model. Bilateral IC lesions were generated by N-methyl-D-day (door) aspartate. After a recovery period of 7 days, 14-day consecutive restraint stress was performed. The visceromotor response to colorectal distension was monitored by recording electromyogram to measure rats׳ visceral sensitivity. Results: We found that bilateral insular cortex lesion could markedly inhibit the formation of visceral hypersensitivity induced by chronic stress. Conclusions: The insular cortex plays a critical role in the pathophysiology of stress-related visceral hypersensitivity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research 10/2014; 220(3):1138-1143. DOI:10.1016/j.psychres.2014.09.019 · 2.68 Impact Factor

Full-text (2 Sources)

Available from
May 26, 2014