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: 16.72). 09/2009; 137(6):1954-62. DOI: 10.1053/j.gastro.2009.08.058
Source: PubMed


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.

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    • "It is well known that early traumatic and painful experiences such as burns can induce long-term alterations in sensory and pain processing in children.21 Similarly, though different from neonatal stress, childhood trauma and abuse that are strongly associated to IBS in adults result in modifications in the hypothalamic-pituitary-adrenal axis.22 However, somatic pain researchers have also shown that long-term consequences of NICU admission are not only characterized by enhanced perceptual sensitization to prolonged painful stimulation but also by hypoalgesia to brief heat pain stimuli23 suggesting that modifications of pain processing may occur in various directions. "
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    ABSTRACT: Functional gastrointestinal disorders (FGID) affect 15%-20% of the general pediatric and adult population. Animal models suggest that a neonatal stress such as invasive procedures and maternal separation could be responsible for visceral hypersensitivity and FGID. We tested the hypothesis that congenital esophageal atresia (EA), a condition corrected during the neonatal period and associated with multiple stresses, is a clinically significant risk factor for the development of FGID later in life. We postulated that, to be clinically significant, the effect of neonatal stress on the incidence of FGID should be as strong as that of enteric infections in the development of irritable bowel syndrome in children. Subjects with EA and healthy controls were enrolled in this multicenter cohort study. Gastrointestinal symptoms were assessed by a questionnaire and FGID was diagnosed using the Rome III criteria. Fifty-three children (25 girls; median age, 12 years) with EA were compared to 72 age- and sex-matched controls. Although 11 children with EA (21%) had a FGID diagnosis versus 8 controls (11%), this difference was not significant (χ(2) = 2.20, P > 0.05). In subjects with EA, the presence of associated malformations, the occurrence of complications during the first month, and the length of hospital stay > 30 days did not influence the incidence of FGID. Chronic abdominal pain was present in 38% of subjects with EA versus 25% of controls (P > 0.05). Neonatal stress secondary to surgical correction of EA is not a clinically significant risk factor for the development of FGID in childhood.
    Full-text · Article · Oct 2012 · Journal of neurogastroenterology and motility
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    • "A significant increase in 5-HT-positive cell number and 5-HT content after CRD stimulation was also observed in the colon of animals, which experienced maternal separation (Ren et al., 2007). Videlock et al. (2009) demonstrated that IBS patients and controls with a history of early adverse life events (EAL) have a greater cortisol response to a visceral stressor compared to individuals without EAL, suggesting the involvement of the HPA axis. "
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    ABSTRACT: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with an estimated prevalence of 10-20%. Current understanding of the pathophysiology of IBS is incomplete due to the lack of a clearly identified pathological abnormality and due to the lack of reliable biomarkers. Possible mechanisms believed to contribute to IBS development and IBS like symptoms include physical stressors, such as infection or inflammation, psychological, and environmental factors, like anxiety, depression, and significant negative life events. Some of these mechanisms may involve the brain-gut axis (BGA). In this article we review the current knowledge on the possible involvement of the BGA in IBS and discuss new directions for potential future therapies of IBS.
    Preview · Article · Jul 2012 · Frontiers in Pharmacology
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    • "Exposure to adverse environments such as inadequate parenting during childhood may lead to serious life-long effects due to impaired brain development and dysregulation of the brain-gut axis [1], [51]. Moreover, chronic sustained stress, particularly as a primary life event, has been demonstrated to be an important factor in both FGID onset and modulation [49], [52]. The mother's parental style during childhood may be associated with dysregulation of emotional inhibition [53], [54] and the onset of GI symptoms [55], [56]. "
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    ABSTRACT: The electrophysiological properties of the brain and influence of parental bonding in childhood irritable bowel syndrome (IBS) are unclear. We hypothesized that children with chronic gastrointestinal (GI) symptoms like IBS may show exaggerated brainstem auditory evoked potential (BAEP) responses and receive more inadequate parental bonding. Children aged seven and their mothers (141 pairs) participated. BAEP was measured by summation of 1,000 waves of the electroencephalogram triggered by 75 dB click sounds. The mothers completed their Children's Somatization Inventory (CSI) and Parental Bonding Instrument (PBI). CSI results revealed 66 (42%) children without GI symptoms (controls) and 75 (58%) children with one or more GI symptoms (GI group). The III wave in the GI group (median 4.10 interquartile range [3.95-4.24] ms right, 4.04 [3.90-4.18] ms left) had a significantly shorter peak latency than controls (4.18 [4.06-4.34] ms right, p = 0.032, 4.13 [4.02-4.24] ms left, p = 0.018). The female GI group showed a significantly shorter peak latency of the III wave (4.00 [3.90-4.18] ms) than controls (4.18 [3.97-4.31] ms, p = 0.034) in the right side. BAEP in the male GI group did not significantly differ from that in controls. GI scores showed a significant correlation with the peak latency of the III wave in the left side (rho = -0.192, p = 0.025). The maternal care PBI scores in the GI group (29 [26]-[33]) were significantly lower than controls (31 [28.5-33], p = 0.010), while the maternal over-protection PBI scores were significantly higher in the GI group (16 [12]-[17]) than controls (13 [10.5-16], p = 0.024). Multiple regression analysis in females also supported these findings. It is suggested that children with chronic GI symptoms have exaggerated brainstem responses to environmental stimuli and inadequate parental behaviors aggravate these symptoms.
    Preview · Article · Mar 2012 · PLoS ONE
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