Causal Links Found Between Schizophrenia, Major Depressive Disorder on IBS

A new study found major depressive disorder (MDD) and schizophrenia have causal effects on irritable bowel syndrome (IBS).¹

The new research provides insight into a debate people have had for decades about whether MDD and schizophrenia have causal effects on IBS. The study also suggests IBS has causal effects on MDD.

“To our knowledge, this is the first MR study to comprehensively evaluate the causal relationship between psychiatric disorders and IBS,” wrote investigators, led by Wang Fan, from the department of gastroenterology at Changhai Hospital, Naval Medical University, in China.

It is believed IBS occurs due to abnormal brain-gut interactions. Due to the potential involvement of the gut-brain axis in pathophysiological mechanisms, the link between neurological disorders and IBS has generated significant interest.

Previous studies demonstrated a strong association between IBS and psychiatric disorders, suggesting stress may trigger or worsen IBS. A systematic review revealed patients who have IBS with mental illness experience more severe and disabling gastrointestinal symptoms. Recent epidemiological data showed two-thirds of patients had IBS before psychological issues and one-third had psychological issues before IBS.

A study published in 2023 examined the rates of psychiatric conditions in 1.2 million IBS patient hospitalizations and found > 38% had anxiety and > 27% had depression.²

“I frequently tell my patients who have IBS, that if they have any type of psychologic stress, it will get expressed in some form or the other,” Yezaz Ghouri, MD, senior author of the 2023 study, told the University of Missouri. Ghouri is an assistant professor of clinical medicine and gastroenterology from the University of Missouri School of Medicine. “The mesentery membrane that holds the intestines together has one of the largest collections of nerve cells in the body. When those nerves start firing impulses, that can lead to the state of nervousness in and around the GI tract, resulting in IBS symptoms.”

Despite evidence of the association between IBS and mental illness, it is not confirmed whether the association is causal, concomitant, or accidental.¹ Thus, investigators performed a Mendelian randomization (MR) analysis to assess the causal effects of several psychiatric disorders on IBS.

The team obtained summary data of genome-wide association studies (GWAS) largely from the Psychiatric Genomics Consortium on individuals of European ancestry. From GAWS, investigators selected single nucleotide polymorphisms linked to 6 psychiatric disorders: schizophrenia, bipolar disorder, MDD, anxiety disorder, panic disorder, and posttraumatic stress disorder (PTSD).

Investigators explained how pulling data from 2 GAWS allowed them to make causal inferences between 2 traits, even when such traits are not from the sample set.

“It enables us to fully leverage the statistical data from various existing GWAS,” investigators wrote.

The analysis used 3 MR methods: inverse-variance weighting, weighted median, and MR-Egger regression. Investigators also used MR-IVW Cochran's Q statistic and MR-Egger intercept to assess heterogeneity and detect directional horizontal pleiotropy, respectively.

In the study, heritability was high for bipolar disorder (81.18%; 95 % confidence interval [CI], 73.18 – 148.18%), schizophrenia (33.88%; 95% CI, 33.57 – 38.19%), and panic disorder (30.66 %; 95 % CI, 20.74 – 40.58%). Conversely, MDD (0.67%; 95% CI, 0.61 –0.73%), anxiety disorder (7.63%; 95% CI, 1.67 – 13.59%), PTSD (0.96%; 95% CI, 0.12 –1.8%), and IBS (2.44%; 95% CI, 2.13 – 2.75%) all had low liability-scale SNP heritability.

The MR-IVW revealed schizophrenia had a significant causal effect on IBS. Investigators noted the individual causal estimates of genetic factors for MDD and schizophrenia were heterogeneous. However, the team did not observe pleiotropic effects.

Ultimately, the study demonstrated a significant bidirectional association between IBS and the psychiatric conditions of MDD and schizophrenia. The data showed the presence of one condition may worsen the other.

“This finding highlights the need for a comprehensive management strategy that addresses both psychiatric and gastrointestinal symptoms in clinical practice,” investigators wrote. “We believe that addressing these questions is crucial for advancing our understanding of the interplay between psychiatric and IBS.”

References

1. ^{Fan W, Liu YL, Jiang CH, et al. Association between psychiatric disorders and irritable bowel syndrome: A bidirectional Mendelian randomization study. J Affect Disord. Published online September 9, 2024. doi:10.1016/j.jad.2024.09.030}
2. ^{Irritable Bowel Syndrome Patients Suffer High Rates of Anxiety and Depression. University of Missouri School of Medicine. February 22, 2023. https://medicine.missouri.edu/news/irritable-bowel-syndrome-patients-suffer-high-rates-anxiety-and-depression. Accessed September 19, 2024.}