Depressive symptoms and single nucleotide polymorphisms predict clinical recurrence of inflammatory bowel disease

Background and Aims Inflammatory bowel disease (IBD) patients are at high risk for depression. We examined interrelations between genetic risk factors for depression, depressive symptoms and IBD flares. Methods In 1973 patients (1137 Crohn's disease, 836 ulcerative colitis) of the Swiss IBD cohort study (SIBDC), 62 single nucleotide polymorphisms (SNPs) preselected for associations with depression, stress, pain and smoking were screened for cross-sectional associations with depression (hospital anxiety and depression subscale for depression, HADS-D[≥]11). Logistic regression and Cox proportional hazards models were built to test for effects of depressive symptoms on disease course and genetic risk factors on depression and disease course. As endpoints we used active disease (CDAI[≥]150 or MTWAI[≥]10) and two published composite flare definitions: FNCE: physician reported flare, non-response to therapy, new complication or extraintestinal manifestation and AFFSST: active disease, physician reported flare, fistula, stenosis and new systemic therapy. Results Depressive symptoms were a strong risk factor for disease related endpoints including active disease (adjusted hazard ratio, aHR: 3.25, p<0.001), AFFSST (aHR: 1.62, p<0.001) and FNCE (aHR: 1.35, p=0.019). Rs588765's TC alleles and rs2522833's C allele were associated with depressive symptoms at baseline (odds ratio, OR: 0.43, q=0.050 and OR: 1.73, q=0.059, respectively). Rs588765-TC remained protective regarding presence of depression (aHR: 0.67, p=0.035) and was associated with fewer active disease states (aHR: 0.72, p=0.045) during follow-up. Conclusions In IBD, genetics, depressive symptoms and inflammatory activity are intimately related: Depressive symptoms were a predictor of clinical deterioration and rs588765-TC was protective for depression and high IBD activity.