Study Background and Disease Burden
Microscopic colitis (MC) is a chronic inflammatory condition affecting the large intestine, primarily detected via microscopic examination of colon biopsies. It predominantly affects middle-aged and older adults and has seen a notable increase in incidence over recent decades. Despite being characterized by symptoms such as chronic watery diarrhea and abdominal discomfort, MC is often underrecognized in clinical practice. Patients with MC frequently report a diminished quality of life, which may relate not only to physical symptoms but potentially to psychological well-being as well. To date, large-scale, population-based evidence on the risk of psychiatric disorders following MC diagnosis has been limited, representing a significant gap given the increasingly recognized gut-brain axis interactions and the known psychosomatic aspects of many gastrointestinal disorders.
Study Design
This investigation was a nationwide, matched cohort study conducted in Sweden between 2006 and 2021, utilizing the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) histopathology database. The study identified 5,816 patients with histologically confirmed MC on colorectal biopsy. These patients were matched to 21,509 reference individuals from the general population, matched by age, sex, and county of residence, all without prior psychiatric diagnoses. Importantly, the analysis excluded individuals with a history of psychiatric disorders to focus on incident cases. The cohort was followed longitudinally for new-onset psychiatric disorders diagnosed by healthcare professionals, classified according to established diagnostic codes. Additionally, a sibling-controlled analysis was performed to account for shared genetic and environmental factors.
Key Findings
During the follow-up period, 519 of the 5,816 patients with MC (median age 64.4 years; interquartile range 49.5-73.3) were diagnosed with a psychiatric disorder, corresponding to an incidence rate of 9.9 per 1,000 person-years. In comparison, 1,313 psychiatric diagnoses occurred among the 21,509 reference individuals, translating to 6.5 events per 1,000 person-years. This difference indicates that there was one additional psychiatric disorder diagnosis for every 29 patients with MC over a 10-year period.
After statistical adjustments for potential confounders, MC was associated with a 57% increased hazard for developing psychiatric disorders (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.42-1.74). This elevated risk was sustained for up to 10 years following MC diagnosis. Notably, the risk was more pronounced in older patients, suggesting an age-related susceptibility.
Subtype analyses revealed that MC patients exhibited significantly increased risks of several psychiatric conditions, including unipolar depression, anxiety disorders, stress-related disorders, substance abuse disorders, and suicide attempts. The sibling-controlled analysis further strengthened these findings, demonstrating a similar heightened risk (adjusted HR 1.76, 95% CI 1.44-2.15), which underscores the potential independent effect of MC beyond familial or genetic predispositions.
Expert Commentary
The study by Bergman et al. represents an important advancement in understanding the neuropsychiatric burden associated with microscopic colitis. Given the robust nationwide design, histopathology-confirmed diagnosis, and comprehensive follow-up, the findings carry substantial epidemiologic weight. They highlight the necessity for clinicians to be vigilant not only about the gastrointestinal symptoms but also the mental health of patients with MC.
Mechanistically, the increased psychiatric risk may be multifactorial. Chronic inflammation, gut microbiota perturbations, and disruptions in the gut-brain axis can influence mood and cognitive function. Additionally, the chronic nature of MC, associated discomfort, and impact on social functioning may contribute to psychological distress.
There are some limitations to consider. Despite adjustment for confounders and sibling comparison, residual confounding cannot be fully excluded. The study population, drawn from Sweden, may limit generalizability to other ethnicities or healthcare settings. Also, the reliance on clinical diagnosis may miss subclinical psychiatric symptoms.
Overall, this work aligns with growing evidence linking gastrointestinal inflammatory conditions to neuropsychiatric comorbidities and advocates for integrated care approaches.
Conclusion
Patients with microscopic colitis bear a significantly increased risk of developing a range of psychiatric disorders, including depression, anxiety, stress-related conditions, substance abuse, and suicide attempts. This heightened risk persists for up to a decade post-diagnosis and is more pronounced with advancing age. Clinicians managing MC should incorporate mental health screening and consider multidisciplinary interventions to improve overall patient outcomes. Future research is warranted to elucidate the pathophysiological mechanisms underlying this association and to identify preventive strategies or tailored therapies to address the mental health needs of this vulnerable population.
References
1. Bergman D, Roelstraete B, Sun J, Ebrahimi F, Butwicka A, Pardi DS, Ludvigsson JF. Psychiatric Disorders Among 5,800 Patients With Microscopic Colitis: A Nationwide Population-Based Matched Cohort Study. Am J Gastroenterol. 2024 Dec 1;119(12):2516-2525. doi: 10.14309/ajg.0000000000002955.
2. Hungin AP, Molloy-Bland M, Claes G, et al. Systematic review: the characteristics of patients with microscopic colitis. Aliment Pharmacol Ther. 2008;27(1):17-28.
3. Hudesman D, Banerjee A, Chan WW. Microscopic Colitis: Diagnosis and Management. Gastroenterol Hepatol (N Y). 2017;13(8):445-452.
4. Foster JA, Neufeld KM. Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013;36(5):305-312.
