Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression

Abstract

ObjectiveDepression is associated with IBD, but the effect of antidepressants on IBD has been sparsely studied. We assessed the impact of depression and antidepressant therapies on the development of IBD.DesignThe Health Improvement Network (THIN) was used to identify a cohort of patients with new-onset depression from 1986 to 2012. THIN patients who did not meet the defining criteria for depression were part of the referent group. The outcome was incident Crohn’s disease (CD) or ulcerative colitis (UC). Cox proportional hazards modelling was performed to evaluate the rate of Crohn’s disease or UC development among patients with an exposure of depression after controlling for age, sex, socioeconomic status, comorbid conditions, smoking, anxiety and antidepressant use including atypical antidepressants, mirtazapine, monoamine oxidase inhibitors (MAOI), serotonin norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), serotonin modulators; and tricyclic antidepressants (TCA).ResultsWe identified 403 665 (7.05%) patients with incident depression. Individuals with depression had a significantly greater risk of developing CD (adjusted HR=2.11, 95% CI 1.65 to 2.70) and UC (adjusted HR=2.23, 95% CI 1.92 to 2.60) after controlling for demographic and clinical covariates. SSRI and TCA were protective against CD, whereas mirtazapine, SNRI, SSRI, serotonin modulators and TCA were protective for UC.ConclusionPatients with a history of depression were more likely to be diagnosed with IBD. In contrast, antidepressant treatments were selectively protective for Crohn’s disease and UC. These results may impact counselling and management of depression and IBD.

The influence of the brain–gut axis in inflammatory bowel disease and possible implications for treatment

“…This may arise via action on the nuclear factor-B and nitric oxide pathways, which are both implicated in the aetiology of IBD. 91 In a large registry-based study, including almost six million primary care patients, with follow-up conducted over a median period of 6.7 years, the presence of depression was associated with an increase in incident diagnoses of both CD and UC. 92 The authors also noted that the risk of developing IBD was attenuated by the use of antidepressant medication, suggesting that targeting psychological disorders may have a beneficial impact on the disease course in patients with an established diagnosis of IBD.…”

Review article: the role of the autonomic nervous system in the pathogenesis and therapy of IBD

“…A similar bi‐directional effect has recently been shown with relation to IBD. Flares and inflammatory symptoms in patients with IBD are more common in those with a mood disorder, patients with depression are more likely to develop IBD and anti‐depressants can be protective against development of the disease . The precise mechanisms leading to this bi‐directional influence are complex and incompletely understood, but have been an area of great interest in recent literature .…”

“…¶¶Vagal nerve fibres enter the abdomen via the diaphragm as two trunks – dorsal and ventral. These divide into further branches; the dorsal and ventral gastric branches that innervate corresponding aspects of the stomach and proximal duodenum, and the dorsal and ventral celiac branches that innervate the small and most of the large intestine, as well as the hepatic branch which innervates the liver, pancreas, distal stomach and the rest of the duodenum . Vagal efferents terminate at all layers of the intestinal wall but do not cross the epithelial layer into the lumen .…”

Genome-wide association study of gastrointestinal disorders reinforces the link between the digestive tract and the nervous system

“…(Figure 4A, 26 Table S15) . 27 Genetic risk score (GRS) prediction 28 infection 17 . From published data, we also found that allele A of SNP rs2976388 is associated with increased 1 PSCA expression (beQTL = 0.73, PeQTL = 8.8E-41), and through SMR analysis, the expression of PSCA decreased 2 risk for PUD (bSMR= -0.12, PSMR = 4.8E-9).…”

“…The ℎ "#$ % estimated on the observed scale were transformed to the liability scale 27 taking the sample lifetime risk (proportion of sample that are cases) as the disease lifetime risk estimates. The 28 summary statistics for each phenotype were filtered using the LDSC default file, w_hm3.snplist, with the 1 default LD scores computed using 1000 Genomes European data (eur_w_ld_chr) as a reference. Genetic 2 correlations (rg) between any two of the six UKB digestion phenotypes or each of the six phenotypes and six 3 published psychiatric traits (attention deficit/hyperactivity disorder (ADHD) 31 , schizophrenia (SCZ) 32 , anxiety 4 disorder 33 , posttraumatic stress disorder (PTSD) 34 , bipolar disorder (BIP) 35 and autism spectrum disorder 5 (ASD) 36 ) were calculated using bivariate LDSC 87 .…”