Irritable bowel syndrome against background of post-traumatic stress disorder: current status of problem and possible solutions

INTRODUCTION. This review article is devoted to the topical issue of studying the relationship between irritable bowel syndrome (IBS) and post-traumatic stress disorder (PTSD). Over the past decade, there has been an increase in the number of patients with a combination of adaptation disorders and functional gastrointestinal tract (GIT) diseases, which requires an in-depth analysis of both the mechanisms underlying this association and an assessment of its impact on patients’ quality of life, as well as the development of preventive and corrective-rehabilitative approaches. This study is a literature review of relevant sources on the epidemiology, pathogenesis, and treatment approaches for this group of pathologies, with an emphasis on finding points of application for antihypoxants/antioxidants and cognitive-behavioral therapy (CBT).

OBJECTIVE. Analysis of pathophysiological mechanisms linking IBS and PTSD and evaluation of promising approaches to comprehensive therapy.

MATERIALS AND METHODS. An analytical review of literary sources in PubMed, Google Scholar, eLibrary, Scopus, Web of Science, Cochrane Library, and CyberLeninka databases for the last 10 years was conducted using the keywords: “CBD,” “PTSD,” “comorbidity,” and “brain-gut axis.” Forty-six articles that met the search criteria were selected. RESULTS. A high prevalence of comorbidity between IBS and PTSD (OR = 4.54; 95% CI: 4.07–5.06) was established, with a predominance of the diarrhea variant of IBS (71%) and more severe symptoms. Key pathophysiological mechanisms were identified: dysregulation of the autonomic nervous system (sympathicotonia), hyperactivation of the hypothalamic-pituitary-adrenal axis and hypercortisolemia, hypoxic changes and oxidative stress in the microbiota, and dysfunction of the brain-gut axis (dysbiosis, systemic inflammation).

DISCUSSION. The comorbidity of IBS and PTSD is a clinically significant condition with common pathogenetic mechanisms. The most promising approach to treatment is an integrative one, combining the use of several main groups: pharmacotherapy (antihypoxants, cytoflavin), psychotherapy (cognitive-behavioral therapy (CBT)).

CONCLUSION. The pathogenesis of comorbidity of IBS and PTSD integrates disturbances in neurovegetative regulation, hypoxia, and dysfunction of the brain-gut axis. The priority direction is the development of combined treatment regimens (antihypoxants + CBT + diet) to influence various links in the pathogenesis.

1. Karchoud J. F., Haagsma J., Karaban, I., Hoeboer, C., van de Schoot, R., Olff, M., & van Zuiden, M. (2024). Long-term PTSD prevalence and associated adverse psychological, functional, and economic outcomes: a 12–15 year follow-up of adults with suspected serious injury. European Journal of Psychotraumatology, 15(1). https://doi.org/10.1080/20008066.2024.2401285

2. Toropova, K. A., Ivashkina O. I., Anokhin K. V. Post-traumatic stress disorder: theoretical approaches and ways of modeling on animals // Pavlov Journal of Higher Nervous Activity. 2021. Vol. 71, No. 6. pp. 735-759. (In Russ.) https://doi.org/10.31857/S0044467721060113. EDN BQFNRL.

3. Kekelidze, Z. I., Portnova A. A. Diagnostic criteria for post-traumatic stress disorder // Journal of Neurology and Psychiatry named after C.C. Korsakov. 2009. Vol. 109, No. 12. pp. 4-7. (In Russ.) EDN LBEVIT.

4. Buono JL, Mathur K, Averitt AJ, Andrae DA. Economic Burden of Irritable Bowel Syndrome with Diarrhea: Retrospective Analysis of a U.S. Commercially Insured Population. J Manag Care Spec Pharm. 2017 Apr;23(4):453-460. doi: 10.18553/jmcp.2016.16138. Epub 2016 Nov 21. PMID: 28345443; PMCID: PMC10398241.

5. Iorio N, Makipour K, Palit A, Friedenberg FK. Post-traumatic Stress Disorder Is Associated With Irritable Bowel Syndrome in African Americans. J Neurogastroenterol Motil. 2014 Oct 30;20(4):523-30. https://doi.org/10.5056/jnm14040. PMID: 25273122; PMCID: PMC4204408.

6. Goldstein RB, Smith SM, Chou SP, et al: The epidemiology of DSM-5 posttraumatic stress disorder in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Soc Psychiatry Psychiatr Epidemiol 51(8):1137-1148, 2016. https://doi.org/10.1007/s00127-016-1208-5

7. Kent KG. The relationship between post-traumatic stress disorder and gastrointestinal disease in United States Military Veterans. SAGE Open Med. 2024 Jun 22;12:20503121241260000. https://doi.org/10.1177/20503121241260000. PMID: 38911441; PMCID: PMC11193927.

8. Orlova A.D. The level of stress tolerance and tendency to anxiety in patients with irritable bowel syndrome // International Student Scientific Bulletin. 2018. No. 5. p. 47. (In Russ.) EDN UZQKYE.

9. Cohen H., Benjamin J., Kaplan Z., Kotler M. Administration of high-dose ketoconazole, an inhibitor of steroid synthesis, prevents posttraumatic anxiety in an animal model. Eur. Neuropsychopharmacol. 2000. 10: 429–435.

10. Cohen H., Kaplan Z., Kotler M. CCK-antagonists in a rat exposed to acute stress: implication for anxiety associated with post-traumatic stress disorder. Depress. Anxiety. 1999. 10(1): 8–17.

11. Cohen H., Kaplan Z., Matar M.A., Loewenthal U., Kozlovsky N., Zohar J. Anisomycin, a protein synthesis inhibitor, disrupts traumatic memory consolidation and attenuates posttraumatic stress response in rats. Biol. Psychiatry. 2006. 60: 767–776.

12. Cohen H., Kozlovsky N., Alona C., Matar M.A., Joseph Z. Animal model for PTSD: from clinical concept to translational research. Neuropharmacology. 2012. 62: 715–724.

13. Cohen H, Kozlovsky N, Matar MA, Kaplan Z, Zohar J. Mapping the brain pathways of traumatic memory: inactivation of protein kinase M zeta in different brain regions disrupts traumatic memory processes and attenuates traumatic stress responses in rats. Eur Neuropsychopharmacol. 2010 Apr;20(4):253-71. https://doi.org/10.1016/j.euroneuro.2009.12.006. Epub 2010 Feb 2. PMID: 20129764.

14. Cohen H., Zohar J. An animal model of posttraumatic stress disorder: the use of cut-off behavioral criteria. Ann. N. Y. Acad. Sci. 2004. 1032: 167–178.

15. Cohen H., Zohar J., Matar M. A., Zeev K., Loewenthal U., Richter-Levin G. Setting apart the affected: the use of behavioral criteria in animal models of post traumatic stress disorder. Neuropsychopharmacology. 2004. 29: 1962–1970.

16. Cohen H., Zohar J., Matar M. The relevance of differential response to trauma in an animal model of posttraumatic stress disorder. Biol. Psychiatry. 2003. 53: 463–473.

17. Cohen H, Jotkowitz A, Buskila D, Pelles-Avraham S, Kaplan Z, Neumann L, Sperber AD. Post-traumatic stress disorder and other co-morbidities in a sample population of patients with irritable bowel syndrome. Eur J Intern Med. 2006 Dec; 17(8):567-71. https://doi.org/10.1016/j.ejim.2006.07.011. PMID: 17142176.

18. Wernersson R., Carlsson J Posttraumatic stress disorder is correlated to irritable bowel syndrome. Ugeskrift for laeger. 2015. 177. 1248-1252.

19. Khramov E.V., Deulin D.V., Kotenev I.O., Pakhalkova A.A. Somatic manifestations in post-traumatic stress disorder. // Modern Foreign Psychology, 2023. Volume 12. No. 3. pp. 64-73. (In Russ.) https://doi.org/10.17759/jmfp.2023120306

20. Smoller, J. The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders. Neuropsychopharmacol 41, 297–319 (2016). https://doi.org/10.1038/npp.2015.266

21. Michopoulos V, Rothbaum AO, Jovanovic T, Almli LM, Bradley B, Rothbaum BO, Gillespie CF, Ressler KJ. Association of CRP genetic variation and CRP level with elevated PTSD symptoms and physiological responses in a civilian population with high levels of trauma. Am J Psychiatry. 2015 Apr;172(4):353-62. https://doi.org/10.1176/appi.ajp.2014.14020263. Epub 2014 Dec 12. PMID: 25827033; PMCID: PMC4440454.

22. Swathi M., Manjusha S., Isatrin J. Vadakkiniath, Gururaj A. Prevalence and correlates of stress, anxiety, and depression in patients with chronic diseases: a cross-sectional study. Middle East Curr Psychiatry 30, 66 (2023). https://doi.org/10.1186/s43045-023-00340-2

23. Gradus JL, Farkas DK, Svensson E, Ehrenstein V, Lash TL, Toft Sørensen H. Posttraumatic Stress Disorder and Gastrointestinal Disorders in the Danish Population. Epidemiology. 2017 May;28(3):354-360. https://doi.org/10.1097/EDE.0000000000000622. PMID: 28099266; PMCID: PMC5523445.

24. Ng QX, Soh AYS, Loke W, Venkatanarayanan N, Lim DY, Yeo WS. Systematic review with meta-analysis: The association between post-traumatic stress disorder and irritable bowel syndrome. J Gastroenterol Hepatol. 2019 Jan;34(1):68-73. https://doi.org/10.1111/jgh.14446. Epub 2018 Sep 10. PMID: 30144372.

25. Volovik M. G., Belova A. N., Kuznetsov A. N., Polevaya A.V., Vorobyeva O. V., Khalak M. E. Virtual reality technologies in the rehabilitation of combat participants with posttraumatic stress disorder (review) // Modern technologies in medicine. 2023. Vol. 15, No. 1. pp. 74-86 (In Russ.) https://doi.org/10.17691/stm2023.15.1.08. – EDN NTPCZA.

26. Smith JP, Bulejko T, Frey LC. The association between posttraumatic stress disorder and irritable bowel syndrome: a systematic review of the literature. J Clin Psychiatry. 2018;79(3):e24.

27. Puhl RM, Telke S, Larson N, Eisenberg ME, Neumark-Stzainer D. Experiences of weight stigma and links with self-compassion among a population-based sample of young adults from diverse ethnic/racial and socio-economic backgrounds. J Psychosom Res. 2020 Jul;134:110134. https://doi.org/10.1016/j.jpsychores.2020.110134. Epub 2020 May 7. PMID: 32413612; PMCID: PMC7384387.

28. Murphy R, Harris B. Can current post-traumatic growth models capture the lived experience of life with a fluctuating chronic illness? Towards a new model. Br J Health Psychol. 2025 Sep;30(3):e70003. https://doi.org/10.1111/bjhp.70003. PMID: 40589134; PMCID: PMC12209698.

29. Wirkner J, Ventura-Bort C, Schwabe L, Hamm AO, Weymar M. Chronic stress and emotion: Differential effects on attentional processing and recognition memory. Psychoneuroendocrinology. 2019 Sep;107:93-97. https://doi.org/10.1016/j.psyneuen.2019.05.008. Epub 2019 May 10. PMID: 31121343.

30. Taché Y, Bonaz B. Corticotropin-releasing factor receptors and stress-related alterations of gut motor function. J Clin Invest. 2007 Jan;117(1):33-40. doi: 10.1172/JCI30085. PMID: 17200704; PMCID: PMC1716215.

31. Brandt L.J., Chey W.D., Foxx-Orenstein A.E., et al. An Evidence-Based Systematic Review of the Management of Irritable Bowel Syndrome American College of Gastroenterology Task Force on IBS). Am J Gastroenterol 2009; 104(Suppl. 1):1-35.

32. Ford A.C., Moayyedy P., Lacy B.E., et al. American College of Gastroenterology Monograph on the Management of Irritable Bowel Syndrome and Chronic Idiopathic Constipation. Am J Gastroenterol 2014; 109(Suppl. 1):2-26.

33. Layer P., Andresen V., Pehl C., et al. Guideline Irritable Bowel Syndrome: Definition, Pathophysiology, Diagnosis and Therapy. Joint Guideline of the German Society for Digestive and Metabolic Diseases (DGVS) and the German Society for Neurogastroenterology and Motility (DGNM). Z Gastroenterol 2011; 49:237-93.

34. Sabaté J.-M., Jouet P. Prise en charge du Syndrome de I’Intestin Irritable (SIL). Conseil de practique. Societé Nationale Française de Gastro-Entérologie, 2013:1-5.

35. Schwartz ES et al. Increased serum interleukin-6 levels are associated with symptom severity in patients with posttraumatic stress disorder comorbid with irritable bowel syndrome // Psychosom Med. 2011;73(5):411–417.

36. Kim YH, Park JM, Kang MJ. Stress-induced alterations in gut microbiota composition and immune function are associated with irritable bowel syndrome symptoms in patients with post-traumatic stress disorder. Brain Behav Immun. 2019;76:185-193.

37. Zhang L, Wang Z, Ma X. The effect of cognitive behavioral therapy combined with anti-hypoxic agents on treatment outcomes in patients with comorbid PTSD and IBS. Clin Psychopharmacol Neurosci. 2022;20(1):34-42.

38. Ivashkin V.T., Maev I.V., Shelygin Yu.A., and others Diagnosis and treatment of irritable bowel syndrome Clinical recommendations of the Russian Gastroenterological Association and the Association of Coloproctologists of Russia. Russian Journal of Gastroenterology, Hepatology, and Coloproctology. 2021. 31(5). C. 74-95. (In Russ.). https://doi.org/10.22416/1382-4376-2021-31-5-74-95

39. Mawdsley JE, Rampton DS. Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut. 2005 Oct;54(10):1481-91. https://doi.org/10.1136/gut.2005.064261. PMID: 16162953; PMCID: PMC1774724.

40. Chang L. The role of stress on physiologic responses and clinical symptoms in irritable bowel syndrome. Gastroenterology. 2011 Mar;140(3):761-5. https://doi.org/10.1053/j.gastro.2011.01.032. Epub 2011 Jan 19. PMID: 21256129; PMCID: PMC3039211.

41. Cryan, J., Dinan, T. Microbiota and neuroimmune signalling—Metchnikoff to microglia. Nat Rev Gastroenterol Hepatol 12, 494–496 (2015). https://doi.org/10.1038/nrgastro.2015.127

42. Sansone RA, Sansone LA. IRRITABLE BOWEL SYNDROME: Relationships with Abuse in Childhood. Innov Clin Neurosci. 2015 May-Jun;12(5-6):34-7. PMID: 26155376; PMCID: PMC4479362.

43. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5®). Arlington, VA: American Psychiatric Publishing; 2013.

44. Zakharov K. I., Belov V. G., Parfenov Yu. A. Behavioral therapy and cytoflavin in the treatment of deforming coxarthrosis in elderly and senile patients // Successes of gerontology. 2016. Vol. 29. No. 5. pp. 816-822 (In Russ.).

45. Parfenov Yu. A., Vasilevskaya M. A., Parfenov S. A. Substantiation of indications for the use of BOS therapy and Cytoflavin in the treatment of neurological complications of osteochondrosis in elderly patients. // Medical news of Georgia. 2018. No. 10 (283). pp. 89-96 (In Russ.).

46. Zakharov K. I., Belov V. G., Parfenov Yu. A. Justification of the use of cytoflavin and cognitive behavioral therapy in the complex treatment of patients in the senior group with deforming coxarthrosis. // The successes of gerontology. 2019. Vol. 32, No. 3. pp. 439-444 (In Russ.).

47. Elkin A. A., Sapozhnikov K. V., Parfenov S. A. The effectiveness of psychopharmacological correction of the functional state of elderly hockey players // Preventive medicine. 2020. Vol. 23, No. 6, pp. 86-90 (In Russ.). https://doi.org/10.17116/profmed20202306286.

48. Chutko L. S., Surushkina S. Yu. It’s Yakovenko. A., Anisimova T. And., Prokopenko S. M. Investigation of the effectiveness of cytoflavin in the treatment of somatoform disorders / et al. // Journal of Neurology and Psychiatry named after C. C. Korsakov. 2017. Vol. 117. No. 1. pp. 21-24 (In Russ.). https://doi.org/10.17116/jnevro20171171121–24

49. Chutko L. S. Somatoform disorders // Medical Council, 2011, No. 1-2, pp. 84-90 (In Russ.).

50. Chutko L. S. Functional neurological disorders / L. S. Chutko, S. Y. Surushkina // Journal of Neurology and Psychiatry named after C. C. Korsakov. 2021. Vol. 121. No. 1. pp. 98-103 (In Russ.). https://doi.org/10.17116/jnevro202112101198

51. Chutko L. S., Surushkina S. Yu., Yakovenko E. A., Rozhkova A.V., Anisimova T. I., Bondarchuk Yu. L. The effectiveness of cytoflavin in the treatment of burnout syndrome // Journal of Neurology and Psychiatry named after C. C. Korsakov. 2015. Vol. 115. No. 10. pp. 66-70 (In Russ.). https://doi.org/10.17116/jnevro201511510166–70

52. Sapozhnikova T. V., Parfenov S. A., Yelkin A. A., Rizakhanov D. M., Rizakhanova O. A. The effect of cytoflavin on the quality of life of patients with functional dyspepsia // Experimental and clinical gastroenterology. 2022. No. 8(204). pp. 133-140 (In Russ.). https://doi.org/10.31146/1682-8658-ecg-204-8-133-140. – EDN UAYRDL.

53. Sapozhnikova T. V., Sapozhnikov K. V., Parfenov S. A., Sedov A.V. Ways to improve the treatment of functional diseases of the gastrointestinal tract // University Therapeutic Journal. 2023. Vol. 5, no. S. pp. 154-155 (In Russ.). – EDN JKKDJU.

54. Sapozhnikova T. V., Parfenov S. A., Esina T. E., Sapozhnikov K. V., Smirnov A. N., Paulov A. A., Rizakhanov D. M., Rizakhanova O. A. The use of antioxidants and cognitive behavioral therapy in patients with functional dyspepsia // Russian Journal of Gastroenterology, Hepatology, and Coloproctology. 2023. Vol. 33, No. 3. pp. 34-42 (In Russ.). https://doi.org/10.22416/1382-4376-2023-33-3-34-42. – EDN MGLXIK.

55. Sperber AD, Mearin F, Shamir R. Rome IV criteria for functional gastrointestinal disorders: new advances and challenges. Nat Rev Gastroenterol Hepatol. 2017;14(1):49-64.