Abstract

BackgroundTo investigate whether anxiety and depression levels are associated with Heat Shock Protein 70 (HSP70) induction in the colon of patients with ulcerative colitis (UC).MethodsThe design was cross-sectional. Clinical activity was assessed by the Rachmilewitz Index (CAI). Three psychometric questionnaires were used: Zung Depression Rating Scale (ZDRS), Spielberg State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS). Colon biopsies were obtained from each affected anatomical site. Severity of inflammation was assessed by eosin/hematoxylin. Constitutive (HSP70c) and inducible (HSP70i) HSP70 expression were immunohistochemically studied.Results29 UC patients were enrolled (69% men). Mean age was 46.5 years (SD: 19.5). Inflammation severity was moderate in 17 patients, severe in 6, and mild in 6. The mean number of years since diagnosis was 7.9 (SD: 6.5). The mean CAI was 6.4 (SD: 3.1). In active UC, there was downregulation of HSP70c in inflamed epithelium, without significant HSP70 induction. In 22/29 cases of active cryptitis, polymorphonuclear cells (PMN) clearly expressed HSP70i, with weak, focal positivity in the other 7 cases. Except for the hospital anxiety scale, scores in all psychometric tools were higher in patients with strong HSP70i immunoreactivity in the PMN. Logistic regression showed a strong positive relationship between HSP70i immunoreactivity in the PMN cells and scores in the trait anxiety, ZDRS, and hospital depression scales, (Odds ratios 1.3, 1.3, and 1.5; P = 0.018, 0.023, and 0.038; Wald test, 5.6, 5.2, and 4.3 respectively) and a weaker but significant positive correlation with the CAI (Odds ratio 1.654; P = 0.049; Wald test 3.858).ConclusionHSP70 is induced in PMN cells of UC patients and its induction correlates with depression and anxiety levels.

Highlights

  • To investigate whether anxiety and depression levels are associated with Heat Shock Protein 70 (HSP70) induction in the colon of patients with ulcerative colitis (UC)

  • UC patients seem to have an increased sympathetic autonomic activity compared to controls, and the severity of their symptoms is associated with measures of personality-related but not situational anxiety [10]

  • Immunohistochemistry - controls For the constitutive HSP70, we found strong nuclear and cytoplasmic expression throughout the epithelium with the same intensity from the surface to the base of the crypts and the MC of the lamina propria (Figure 1a, c, e)

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Summary

Introduction

To investigate whether anxiety and depression levels are associated with Heat Shock Protein 70 (HSP70) induction in the colon of patients with ulcerative colitis (UC). Its etiology remains unknown, there is evidence of an aberrant response of Psychological stress and depression are known to prolong the clinical course of UC in terms of symptom severity and relapses [2,3,4] and it seems that UC patients, compared to the general population, are significantly more likely to have a diagnosis of anxiety and major depression [5,6]. Identical twin studies reveal smaller genetic predisposition for the etiology of UC (10%), compared to the 50% genetic predisposition of identical twins with CD [11]. In this light, the theory of neuroimmunomodulation in UC requires further documentations [12,13]

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