The Role Of Stress And Coping Behavior In Inflammatory Bowel Disease

Background As the bio-medical model developing into bio-psycho-social medical model, more and more attentions were paid to the role of psychosocial factors in disease occurrence and evolution. Among digestive diseases, the correlation of psychological stress and upper digestive tract ulcer has been confirmed; and stress is very closely associated with irritable bowel syndrome (IBS). As for inflammatory bowel disease (IBD), the influence caused by psychological stress has become eye-catching in recent studies. In population-based survey, the psychological stress and maladjustment were found to be related to lower quality of life in IBD patients. Researchers also found that pressure control training was benefit to IBD patients. However, in Chinese patients, perceived stress and medical coping behaviors were not fully investigated, the mechanism of stress in IBD also need further research.Aims Firstly, we aimed to further understand the role of perceived stress and coping modes in Chinese patients with IBD. Secondly, we aimed to find differences and similarities of transcriptome profile in colonic mucosa between ulcerative colitis (UC) and IBS. Thirdly, we aimed to build a mice model showing impact of stress on DSS-induced colitis, and find differences of microRNA expression in colon tissues after stress stimuli.Methods In the first part, outpatients and inpatients with IBD in Peking Union Medical College Hospital from June 2013 to February 2015 were recruited. Demographic and clinical data including disease course, activity, as well as phenotype according to Montreal classification were collected. Quality of life was measured by Inflammatory Bowel Disease Questionnaire (IBDQ). Perceived stress was measured by Perceived Stress Scale (PSS). Coping strategy was evaluated by Medical Coping Modes Questionnaire (MCMQ). One year later, follow-ups were done checking on relapses and hospitalizations. Univariate analyses were conducted to determine which variables were associated with perceived stress, coping modes, quality of life and hospitalization within one year follow-up respectively. And multivariate analyses were used to find independent factors. In the second part, PSS and sigmoid mucosa biopsy were carried out in 5 UC patients,5 IBS patients, and 5 healthy controls, transcriptome profile was gained by RNA-sequencing, and correlation of different gene expressions and PSS scores were evaluated. In the third part, repeated forced swimming and restraint stress was used to build a mice model to prove stress can exacerbate DSS-induced colitis. SIRT1 and SIRT6 mRNA levels were detected by qRT-PCR. And Affimetrix 4.0 microRNA chips were used to determine different microRNA expression after stress stimuli.Results In the first part, A total of 422 patients were recruited, with 258 UC and 164 CD patients. On one hand, in CD patients, working status, such as unemployed or laid-off is an independent factor related to perceived stress (F 4.149, p=0.044). And perceived stress, acceptance and poor quality of life were related to each other closely (p<0.01). However, clinical activity was the main factor influence patients’quality of life and hospitalization in one year (p<0.05). On the other hand, in UC patients, female was an independent factor related to perceived stress (F 7.421, p=0.007). Perceived stress was related to acceptance and poor quality of life (p=0.000). Acceptance (OR 0.272,95%CI 0.077-0.963) and poor quality of life (OR 2.985,95%CI 1.058-8.421) were independent risk factors to hospitalization in one year. In the second part,1641 genes were differently expressed between UC patients and healthy controls,1445 genes were differently expressed between UC and IBS patients. While only 131 different genes were found between IBS patients and healthy controls. There are 83 common distinct genes in UC and IBS, and 9 of them were related to behavior functions. The expression of 10 genes were related to perceived stress. PYY, EGR1, DYNC1H1, BCHE might involve with stress induced gastrointestinal change. In the third part, DSS-induced colitis became severe after stress, SIRT1 and SIRT6 mRNA levels decreased slightly in stress group. Through microRNA chips survey,46 microRNAs were down-regulated in stress group, among them, miR-20b and miR-106a were the most significantly different microRNAs.Conclusions Perceived stress and medical coping modes had an impact on quality of life and prognosis in IBD patients, especially in UC patients. The transcriptome profile of UC was significantly different from those of IBS and healthy controls. The expression of gene PYY, EGR1, DYNC1H1, BCHE may be related to the stress mechanism. Stress deteriorated DSS-induced colitis in mice, and miR-17 family members might be involved in stress mechanism.