Interplay Between Depression and Inflammatory Bowel Disease: Shared Pathogenetic Mechanisms and Reciprocal Therapeutic Impacts—A Comprehensive Review
Abstract
1. Introduction
2. Psychiatric Comorbidity Prevalence and Incidence in IBD
3. Shared Molecular Mechanisms
3.1. Genetic Susceptibility
3.2. Gut Microbiota Dysbiosis
3.3. Immunological Dysregulation
3.4. Hypothalamic–Pituitary–Adrenal (HPA) Disorders
4. Bidirectional Impact of Medications in Inflammatory Bowel Disease and Depressive Disorders
4.1. Impact of Medications Used in IBD on DDs
4.2. Impact of Depression Medications on IBD
Study Design | Sample Size | Main Points | Ref. |
---|---|---|---|
Retrospective, observational study | 29 IBD patients (14 UC, 15 CD) | Antidepressants (80% represented by SSRI) seemed to reduce relapse rates. | [138] |
Prospective, observational study | 26 CD patients | Fluoxetine (SSRI) was not superior to placebo in maintaining remission. | [153] |
Prospective, observational study | 67 IBD patients (31 CD, 36 UC) | Antidepressive drug treatment (SSRI 48.4%, SNRI 8.7%, NDRI 12.3%, NaSSA 12.3%, and combination therapies 17.5%) was associated with an improvement in depression, anxiety, QoL, and sexual functioning scores, as well as an improvement in Crohn’s disease activity index. | [139] |
Randomized, double-blind, controlled clinical trial | 44 IBD patients | Duloxetine (SNRI) was effective to reduce depression, anxiety, and severity of disease symptoms and to increase physical, psychological, and social dimensions of QoL | [144] |
A prospective, randomized, double-blind, placebo-controlled clinical trial | 45 IBD patients | Venlafaxine (SNRI) significantly improved QoL, anxious and depressive symptoms, and the activity of IBD. | [154] |
Population-based cohort study | 42,890 IBD patients (69.5% UC; 30.5% CD) | Antidepressant users (SSRI 53.4%, TCA 21.6%, SNRI 14.3%, mirtazapine 8.7%, and other antidepressants 2%) had a significantly lower relapse rate than nonusers, particularly in patients with no use of antidepressants before IBD onset. | [142] |
Retrospective cohort study | 29,393 IBD patients, (42.2% CD, 57.8% UC) | Antidepressants use SSRI 66.2%, SNRI 13.5%, TCA 10.8%, other antidepressants 9.5%) was independently associated with corticosteroid use, visits, and hospitalizations but was negatively associated with surgery and IBD-related complications. | [146] |
Retrospective cohort study | 81 IBD patients (58 CD, 23 UC) and 77 IBS patients | TCA led to moderate improvement of residual GI symptoms in IBD patients, particularly in UC pts. This result was similar to IBS patients. | [143] |
5. Conclusions
6. Future Perspectives
7. Limitations
Author Contributions
Funding
Conflicts of Interest
References
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Cytokine | Role | DDs | IBD | References | |
---|---|---|---|---|---|
CD | UC | ||||
IL-1β | Costimulation in an inflammatory microenvironment | ↑ | ↑ | ↑ | [99,100,101] |
IL-2 | Promotes T cell proliferation | ↑ | - | ↓ | [101,102] |
IL-4 | Induces B cell activation, IgE switch, and differentiation toward Th2 cells | ↓ | - | - | [101] |
IL-5 | Promotes eosinophil growth, differentiation | ↑ | ↑ | ↑ | [101,103] |
IL-6 | Induces T and B cell growth and differentiation, acute phase production, fever | ↑ | ↑ | ↑ | [99,101,104] |
IL-7 | Induces growth of preB-cells and preT-cells | ↑ | - | - | [105] |
IL-8 | Neutrophils and T cells chemotactic factor. | varies | ↑ | ↑ | [101,106,107] |
IL-9 | Induces mast cell activity, stimulates Th cells | ↑ | ↑ | ↑ | [105,108] |
IL-10 | Inhibits cytokine synthesis, anti-inflammatory activity | ↓ | ↓ | ↓ | [109,110] |
IL-11 | Stromal cell regulation of fibrosis | - | ↑ | varies | [111,112] |
IL-12 | NK-cell-stimulating factor, activates and proliferates Th1 cells | ↑ | ↑ | ↑ | [101,113] |
IL-13 | Induces B cell growth and differentiation, induces allergy/asthma | ↑ | - | - | [101] |
IL-15 | IL-2-like cytokine, T cell and NK cell growth factor, enhances memory CD8 T cell survival | ↑ | ↑ | ↑ | [105,114] |
IL-17A | Proinflammatory, induces cytokine production by epithelia, endothelia, astrocytes, and fibroblasts | ↑ | ↑ | ↑ | [101,115] |
IL-18 | Induces IFN-γ production by T cells and NK cells, promotes Th1 induction | ↑ | ↑ | ↑ | [101,116] |
IL-21 | Th17 differentiation, B cell homeostasis | no change | ↑ | ↑ | [117,118] |
IL-33 | Involved in type 2 immunity and allergic airway diseases | ↓ | ↑ | ↑ | [119,120] |
TGFβ1 | Anti-inflammatory factor, contributing to immune response regulation and overall homeostasis. | no change | ↑ | ↑ | [101,121] |
TNF | Promotes inflammation, endothelial activation | ↑ | ↑ | ↑ | [99,101,122] |
IFN-γ | Induces macrophage activation, increased expression of MHC molecules and antigen processing components, and immunoglobulin class switching, suppresses Th2 cells | varies | ↑ | ↑ | [101,123] |
Study Design | Sample Size | Main Points | Ref. |
---|---|---|---|
Prospective cohort study | 160 IBD patients (49 anti-TNFs, 111 vedolizumab) | VEDO and anti-TNFs were associated with improvement in sleep and mood quality in IBD | [138] |
Phase III, randomized, double-blind clinical trial | 492 CD patients | At week 56, the group treated with ADA had a statistically significantly lower percentage of patients with depression than the placebo group | [139] |
Double-blind, cross-over RCT | 104 CD patients | The second most common APE in patients treated with USTE was depression (N = 2; 1.53%) | [136] |
Phase III, randomized, parallel-group, double-blind, placebo-controlled trial | 967 CD patients | Two patients treated with VEDO developed depression (0.21%), and two VEDO-treated patients (0.21%) expressed suicidality | [137] |
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Di Petrillo, A.; Favale, A.; Onali, S.; Kumar, A.; Abbracciavento, G.; Fantini, M.C. Interplay Between Depression and Inflammatory Bowel Disease: Shared Pathogenetic Mechanisms and Reciprocal Therapeutic Impacts—A Comprehensive Review. J. Clin. Med. 2025, 14, 5522. https://doi.org/10.3390/jcm14155522
Di Petrillo A, Favale A, Onali S, Kumar A, Abbracciavento G, Fantini MC. Interplay Between Depression and Inflammatory Bowel Disease: Shared Pathogenetic Mechanisms and Reciprocal Therapeutic Impacts—A Comprehensive Review. Journal of Clinical Medicine. 2025; 14(15):5522. https://doi.org/10.3390/jcm14155522
Chicago/Turabian StyleDi Petrillo, Amalia, Agnese Favale, Sara Onali, Amit Kumar, Giuseppe Abbracciavento, and Massimo Claudio Fantini. 2025. "Interplay Between Depression and Inflammatory Bowel Disease: Shared Pathogenetic Mechanisms and Reciprocal Therapeutic Impacts—A Comprehensive Review" Journal of Clinical Medicine 14, no. 15: 5522. https://doi.org/10.3390/jcm14155522
APA StyleDi Petrillo, A., Favale, A., Onali, S., Kumar, A., Abbracciavento, G., & Fantini, M. C. (2025). Interplay Between Depression and Inflammatory Bowel Disease: Shared Pathogenetic Mechanisms and Reciprocal Therapeutic Impacts—A Comprehensive Review. Journal of Clinical Medicine, 14(15), 5522. https://doi.org/10.3390/jcm14155522