From gut inflammation to psychiatric comorbidity: mechanisms and therapies for anxiety and depression in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by complex aetiological factors and extensive extraintestinal manifestations. Anxiety and depression, which are common mental disorders, have shown increasing incidence rates in recent years. Compared with the general population, IBD patients are more susceptible to anxiety and depression, which consequently exacerbate the disease burden and increases the risk of adverse clinical outcomes. Emerging evidence reveals shared pathophysiological mechanisms between IBD and anxiety and depression. This review rigorously focuses on anxiety and depression in IBD, distinguishing these conditions from primary anxiety or depressive disorders, as well as from mood disturbances secondary to other chronic illnesses, and summarizes the latest research literature highlighting their unique comorbid characteristics. Firstly, we integrate recent epidemiological evidence to establish their bidirectional relationship. Subsequently, we summarize the comorbid mechanisms as follows: genetic predisposition, impaired hippocampal neurogenesis, specific brain region alterations, gut microbiota dysbiosis, hypothalamic‒pituitary‒adrenal (HPA) axis dysregulation and neuroimmune interactions mediated by inflammatory cytokines and neurotransmitters. Finally, we explore novel therapeutic approaches derived from these mechanistic insights, aiming to enhance clinical recognition of this bidirectional comorbidity and optimize the management of such comorbid conditions.

Keywords: Anxiety; Depression; Inflammatory bowel disease; Microbiota‒gut‒brain axis; Neuroimmune; Pharmacotherapy.

Fig. 1

Underlying mechanisms of IBD and anxiety/depression comorbidity. This schematic outlines the numerous changes observed in IBD patients with anxiety/depression and in IBD animal models. ↑ indicates an increase in the related process compared to the healthy control group, ↓ indicates the opposite, and -- indicates no significant difference. The figure was created using Figdraw (ID: PSPYUb4000)

Fig. 2

Hippocampal neurogenesis associated with anxiety and depression in IBD. This figure illustrates recent advances in hippocampal neurogenesis across psychiatric disorders (anxiety and depression) and anxiety/depression combined with IBD, highlighting alterations in neurogenesis and their effects on anxiety- and depression-like behaviours. The left side (orange) primarily showcases research on hippocampal neurogenesis in psychiatric disorders, such as anxiety and depression, across various species. The right side (green) focuses on key findings from hippocampal neurogenesis in IBD animal models, both acute (top right) and chronic (bottom right) colitis. It analyzes the abnormalities in hippocampal neurogenesis and their impact on behavior associated with anxiety and depression in IBD, synthesizing both consistent and conflicting results across studies. ↑ indicates promotion; ↓ indicates inhibition; → indicates the resulting effect. For the abbreviations, refer to the list of Abbreviations