Childhood trauma is associated with hypothalamic-pituitary-adrenal axis responsiveness in irritable bowel syndrome

Abstract

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 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).

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.

Figure 1

Salivary cortisol response to a visceral stressor (flexible sigmoidoscopy [FS]) for IBS and controls (A), subjects with and without EAL (B), subjects broken intro groups by diagnosis and presence of EAL (C), and by sex and EAL (D). Presence of EAL (B) had a significant effect on the cortisol response (p < 0.05). * indicates that there is a significant difference between the groups at that time point in post-hoc analyses. In C, the EAL groups were significantly greater than IBS and controls without EAL, and in D, the men with EAL were significantly greater than men without EAL. Where shown, error bars represent the 95% confidence interval around the mean.

Figure 2

Summary measures of cortisol response. The AUCg (A) is the area under the curve to the x-axis, and the AUCm (B) is the area under the curve to a horizontal line at the minimum value for that subject. The response resolution rate (C) is the decrease in cortisol from peak to baseline after the stressor divided by the time elapsed between the two points. All measures are greater in individuals with EAL (p < 0.05).