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.

Epilepsy is one of the most common chronic neurological disorders. This study aimed to identify hippocampal neuronal subpopulations with the most prominent transcriptional alterations during the latent period following status epilepticus, thereby elucidating early molecular mechanisms of epileptogenesis in a pilocarpine-induced model. Status epilepticus (SE) was induced in male C57BL/6 N mice via intraperitoneal pilocarpine injection, and hippocampal tissue was collected on Day 7 post-SE (n = 3 per group) for single-nucleus RNA sequencing using a 10× Genomics platform. Data were processed using Seurat, clustered via UMAP, and analysed for differential gene expression and KEGG pathway enrichment. From 76,412 high-quality nuclei, we identified 45,584 excitatory neurons, 5,897 inhibitory neurons, and major glial subtypes. Dentate gyrus (DG) excitatory neurons exhibited the most profound transcriptional remodelling, segregating into control-enriched (DG1) and epilepsy-enriched (DG2) factions. The expression of Sorcs3, Rgs6, and Galntl6 was upregulated in DG2 neurons, whereas the expression of Trpc5, Itpr1, and Calb1 was upregulated in DG1 neurons. Among inhibitory neurons, Meis2-expressing interneurons showed the greatest change in relative abundance, with the Meis2-1 subtype tending to increase in relative abundance post-SE compared to controls (P = 0.0728, not significant) and selectively expressing the seizure-related genes Cpa6, Ano1, and Ano2. DG excitatory neurons and Meis2-positive inhibitory neurons represent the most prominently altered hippocampal cell types following seizures, highlighting their potential role in epileptogenic network reorganization. The identification of disease-specific molecular signatures within these populations provides a prioritised framework for investigating causal mechanisms and developing cell type-targeted therapeutic strategies for precision epilepsy treatment.