Gastroenterology

Gastroenterology

Volume 137, Issue 6, December 2009, Pages 1954-1962
Gastroenterology

Clinical—Alimentary Tract
Childhood Trauma Is Associated With Hypothalamic-Pituitary-Adrenal Axis Responsiveness in Irritable Bowel Syndrome

https://doi.org/10.1053/j.gastro.2009.08.058Get rights and content

Background & Aims

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.

Methods

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.

Results

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 μg/dL; P = .003) and higher area under the curve (28.1 ± 17 vs 18.6 ± 13 μg × 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).

Conclusions

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.

Section snippets

Study Subjects and Recruitment

IBS patients age 18–55 years were recruited from specialty clinics and community advertisements, fulfilled ROME II29 diagnostic criteria, and diagnosis was confirmed by a gastroenterologist with expertise in IBS (L.C.). Healthy controls were recruited by newspaper or Internet advertisement from the community, did not have a history of IBS, other chronic pain conditions, or psychiatric illness, and were not taking centrally acting drugs (anxiolytics, narcotics, or antidepressants). None of the

Subject Characteristics

The characteristics of the subjects are summarized in Table 1. The IBS patients included 26 women and 19 men, and the control group included 22 healthy women and 19 healthy men. The IBS patients had higher HAD anxiety and depression scores than controls. There were 3 subjects without data on EAL, and there were 7 additional subjects who were eliminated from AUC analysis because of incomplete cortisol data (women: 1 control without EAL, 2 IBS [1 without EAL, 1 with sexual abuse]; men: 2 controls

Discussion

In the present study, we have shown that in response to a visceral stressor: (1) IBS patients and controls with EALs have a greater cortisol response compared with individuals without EALs; (2) this difference was more pronounced among men than women; (3) IBS patients and controls have similar salivary cortisol responses; (4) among IBS patients with EALs, there was a trend to have higher cortisol levels immediately after the stressor; and (5) in IBS, a slower return of stimulated cortisol to

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by National Institutes of Health grants P50 DK64539 (E.A.M., L.C.), R01 AR46122 (L.C.), R24 AT002681 (E.A.M.), and GCRC M01-RR00865.

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