Skip to main content Accessibility help
×
×
Home

Gut–brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease

  • Áine Abautret-Daly (a1) (a2), Elaine Dempsey (a1) (a2), Adolfo Parra-Blanco (a3), Carlos Medina (a3) (a4) and Andrew Harkin (a1) (a2)...

Abstract

Introduction

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder characterised by inflammation of the gastrointestinal tract. There is a growing consensus that IBD is associated with anxiety- and depression-related symptoms. Psychological symptoms appear to be more prevalent during active disease states with no difference in prevalence between Crohn’s disease and ulcerative colitis. Behavioural disturbances including anxiety- and depression-like symptoms have also been observed in animal models of IBD.

Results

The likely mechanisms underlying the association are discussed with particular reference to communication between the gut and brain. The close bidirectional relationship known as the gut–brain axis includes neural, hormonal and immune communication links. Evidence is provided for a number of interacting factors including activation of the inflammatory response system in the brain, the hypothalamic–pituitary–adrenal axis, and brain areas implicated in altered behaviours, changes in blood brain barrier integrity, and an emerging role for gut microbiota and response to probiotics in IBD.

Discussion

The impact of psychological stress in models of IBD remains somewhat conflicted, however, it is weighted in favour of stress or early stressful life events as risk factors in the development of IBD, stress-induced exacerbation of inflammation and relapse.

Conclusion

It is recommended that patients with IBD be screened for psychological disturbance and treated accordingly as intervention can improve quality of life and may reduce relapse rates.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Gut–brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Gut–brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Gut–brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease
      Available formats
      ×

Copyright

Corresponding author

*Andrew Harkin, School of Pharmacy & Pharmaceutical Sciences and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland. Tel: +353 1 896 8575; Fax: +353 1 896 2821; E-mail: aharkin@tcd.ie

Footnotes

Hide All

Áine Abautret-Daly and Elaine Dempsey contributed equally to this work.

Footnotes

References

Hide All
1. Vavricka, SR, Schoepfer, A, Scharl, M, Lakatos, PL, Navarini, A, Rogler, G. Extraintestinal manifestations of inflammatory bowel disease. Inflamm Bowel Dis 2015;21:19821992.
2. Kim, ER, Chang, DK. Colorectal cancer in inflammatory bowel disease: the risk, pathogenesis, prevention and diagnosis. World J Gastroenterol 2014;20:98729881.
3. Lennard-Jones, JE. Classification of inflamm bowel disease. Scand J Gastroenterol 1989;24(Suppl. 170):26.
4. Baumgart, DC, Sandborn, WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 2007;369:16411657.
5. Lonnfors, S, Vermeire, S, Greco, M, Hommes, D, Bell, C, Avedano, L. IBD and health-related quality of life – discovering the true impact. J Crohns Colitis 2014;8:12811286.
6. Johnston, RD, Logan, RF. What is the peak age for onset of IBD? Inflamm Bowel Dis 2008;14(Suppl. 2):S4S5.
7. Carter, MJ, Lobo, AJ, Travis, SPL. Guidelines for the management of inflammatory bowel disease in adults. Gut 2004;53(Suppl. 5):v1v16.
8. Mowat, C, Cole, A, Windsor, A et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60:571607.
9. Hwang, JM, Varma, MG. Surgery for inflammatory bowel disease. World J Gastroenterol 2008;14:26782690.
10. Sica, GS, Biancone, L. Surgery for inflammatory bowel disease in the era of laparoscopy. World J Gastroenterol 2013;19:24452448.
11. Card, T, Hubbard, R, Logan, RFA. Mortality in inflammatory bowel disease: a population-based cohort study. Gastroenterology 2003;125:15831590.
12. Straker, M. Ulcerative colitis: recovery of a patient with brief psychiatric treatment. Can Med Assoc J 1960;82:12241227.
13. Daniels, GE. Psychiatric aspects of ulcerative colitis. N Engl J Med 1942;226:178184.
14. Sullivan, AJ, Chandler, CA. Ulcerative colitis of psychogenic origin: a report of six cases. Yale J Biol Med 1932;4:779796.
15. Murray, CD. Psychogenic factors in the etiology of ulcerative colitis and bloody diarrhea. Am J Med Sci 1930;180:239247.
16. Farrokhyar, F, Marshall, JK, Easterbrook, B, Irvine, EJ. Functional gastrointestinal disorders and mood disorders in patients with inactive inflammatory bowel disease: prevalence and impact on health. Inflamm Bowel Dis 2006;12:3846.
17. Guthrie, E, Jackson, J, Shaffer, J, Thompson, D, Tomenson, B, Creed, F. Psychological disorder and severity of inflammatory bowel disease predict health-related quality of life in ulcerative colitis and Crohn’s disease. Am J Gastroenterol 2002;97:19941999.
18. Addolorato, G, Capristo, E, Stefanini, GF, Gasbarrini, G. Inflammatory bowel disease: a study of the association between anxiety and depression, physical morbidity, and nutritional status. Scand J Gastroenterol 1997;32:10131021.
19. Mikocka-Walus, A, Knowles, SR, Keefer, L, Graff, L. Controversies revisited: a systematic review of the comorbidity of depression and anxiety with inflammatory bowel diseases. Inflamm Bowel Dis 2016;22:752762.
20. Gandhi, S, Jedel, S, Hood, MM, Mutlu, E, Swanson, G, Keshavarzian, A. The relationship between coping, health competence and patient participation among patients with inactive inflammatory bowel disease. J Crohns Colitis 2014;8:401408.
21. Goodhand, JR, Wahed, M, Mawdsley, JE, Farmer, AD, Aziz, Q, Rampton, DS. Mood disorders in inflammatory bowel disease: relation to diagnosis, disease activity, perceived stress, and other factors. Inflamm Bowel Dis 2012;18:23012309.
22. Addolorato, G, Mirijello, A, D’Angelo, C et al. State and trait anxiety and depression in patients affected by gastrointestinal diseases: psychometric evaluation of 1641 patients referred to an internal medicine outpatient setting. Int J Clin Pract 2008;62:10631069.
23. Calvet, X, Gallardo, O, Coronas, R et al. Remission on thiopurinic immunomodulators normalizes quality of life and psychological status in patients with Crohn’s disease. Inflamm Bowel Dis 2006;12:692696.
24. Clark, JG, Srinath, AI, Youk, AO et al. Predictors of depression in youth with Crohn disease. J Pediatr Gastroenterol Nutr 2014;58:569573.
25. Bokemeyer, B, Hardt, J, Huppe, D et al. Clinical status, psychosocial impairments, medical treatment and health care costs for patients with inflammatory bowel disease (IBD) in Germany: an online IBD registry. J Crohns Colitis 2013;7:355368.
26. Ben Thabet, J, Charfi, N, Mnif, L et al. Emotional disorders and inflammatory bowel disease. Tuni Med 2012;90:557563.
27. Cawthorpe, D, Davidson, M. Temporal comorbidity of mental disorder and ulcerative colitis. Perm J 2015;19:5257.
28. Horst, S, Chao, A, Rosen, M et al. Treatment with immunosuppressive therapy may improve depressive symptoms in patients with inflammatory bowel disease. Dig Dis Sci 2015;60:465470.
29. Keeton, RL, Mikocka-Walus, A, Andrews, JM. Concerns and worries in people living with inflammatory bowel disease (IBD): a mixed methods study. J Psychosom Res 2015;78:573578.
30. Kinsinger, SW, Ballou, S, Keefer, L. Snapshot of an integrated psychosocial gastroenterology service. World J Gastroenterol 2015;21:18931899.
31. Long, MD, Kappelman, MD, Martin, CF, Chen, W, Anton, K, Sandler, RS. Risk factors for depression in the elderly inflammatory bowel disease population. J Crohns Colitis 2014;8:113119.
32. Maconi, G, Gridavilla, D, Vigano, C et al. Perianal disease is associated with psychiatric co-morbidity in Crohn’s disease in remission. Int J Colorectal Dis 2014;29:12851290.
33. Szigethy, E, Bujoreanu, SI, Youk, AO et al. Randomized efficacy trial of two psychotherapies for depression in youth with inflammatory bowel disease. J Am Acad Child Adolesc Psychiatry 2014;53:726735.
34. Szigethy, EM, Youk, AO, Benhayon, D et al. Depression subtypes in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2014;58:574581.
35. Virta, LJ, Kolho, KL. Antidepressant use among paediatric patients with recent-onset inflammatory bowel disease: a nationwide case control study in Finland. J Paediatr Child Health 2014;50:562565.
36. Vlachos, II, Barbatis, C, Tsopanomichalou, M et al. Correlation between depression, anxiety, and polymorphonuclear cells’ resilience in ulcerative colitis: the mediating role of heat shock protein 70. BMC Gastroenterol 2014;14:77.
37. Ananthakrishnan, AN, Khalili, H, Pan, A et al. Association between depressive symptoms and incidence of Crohn’s disease and ulcerative colitis: results from the Nurses’ Health Study. Clin Gastroenterol Hepatol 2013;11:5762.
38. Guloksuz, S, Wichers, M, Kenis, G et al. Depressive symptoms in Crohn’s disease: relationship with immune activation and tryptophan availability. PloS One 2013;8:e60435.
39. Knowles, SR, Wilson, J, Wilkinson, A et al. Psychological well-being and quality of life in Crohn’s disease patients with an ostomy: a preliminary investigation. J Wound Ostomy Continence Nurs 2013;40:623629.
40. Langhorst, J, Hofstetter, A, Wolfe, F, Hauser, W. Short-term stress, but not mucosal healing nor depression was predictive for the risk of relapse in patients with ulcerative colitis: a prospective 12-month follow-up study. Inflamm Bowel Dis 2013;19:23802386.
41. Schuman, SL, Graef, DM, Janicke, DM, Gray, WN, Hommel, KA. An exploration of family problem-solving and affective involvement as moderators between disease severity and depressive symptoms in adolescents with inflammatory bowel disease. J Clin Psychol Med Settings 2013;20:488496.
42. Selinger, CP, Lal, S, Eaden, J et al. Better disease specific patient knowledge is associated with greater anxiety in inflammatory bowel disease. J Crohns Colitis 2013;7:e214e218.
43. Shiga, H, Miyazawa, T, Kinouchi, Y et al. Life-event stress induced by the Great East Japan Earthquake was associated with relapse in ulcerative colitis but not Crohn’s disease: a retrospective cohort study. BMJ Open 2013;3:e002294.
44. Besharat, S, Amiriani, T, Roshandel, G, Besharat, M, Semnani, S, Kamkar, M. Depressive mood and disease activity in inflammatory bowel disease. Arab Journal Gastroenterol 2012;13:136138.
45. Goodhand, JR, Greig, FI, Koodun, Y et al. Do antidepressants influence the disease course in inflammatory bowel disease? A retrospective case-matched observational study. Inflamm Bowel Dis 2012;18:12321239.
46. Loftus, EV Jr., Guerin, A, Yu, AP et al. Increased risks of developing anxiety and depression in young patients with Crohn’s disease. Am J Gastroenterol 2011;106:16701677.
47. Iglesias, M, Barreiro de Acosta, M, Vazquez, I et al. Psychological impact of Crohn’s disease on patients in remission: anxiety and depression risks. Rev Esp Enferm Dig 2009;101:249257.
48. Vidal, A, Gomez-Gil, E, Sans, M et al. The impact of anxiety and depression on relapse in patients with inflammatory bowel disease. Med Clin 2009;132:298302.
49. Vidal, A, Gomez-Gil, E, Sans, M et al. Health-related quality of life in inflammatory bowel disease patients: the role of psychopathology and personality. Inflamm Bowel Dis 2008;14:977983.
50. Walker, JR, Ediger, JP, Graff, LA et al. The Manitoba IBD cohort study: a population-based study of the prevalence of lifetime and 12-month anxiety and mood disorders. Am J Gastroenterol 2008;103:19891997.
51. Janke, KH, Klump, B, Gregor, M, Meisner, C, Haeuser, W. Determinants of life satisfaction in inflammatory bowel disease. Inflamm Bowel Dis 2005;11:272286.
52. Persoons, P, Vermeire, S, Demyttenaere, K et al. The impact of major depressive disorder on the short- and long-term outcome of Crohn’s disease treatment with infliximab. Aliment Pharmacol Ther 2005;22:101110.
53. Mardini, HE, Kip, KE, Wilson, JW. Crohn’s disease: a two-year prospective study of the association between psychological distress and disease activity. Dig Dis Sci 2004;49:492497.
54. Mittermaier, C, Dejaco, C, Waldhoer, T et al. Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study. Psychosom Med 2004;66:7984.
55. Kurina, LM, Goldacre, MJ, Yeates, D, Gill, LE. Depression and anxiety in people with inflammatory bowel disease. J Epidemiol Community Health 2001;55(10):716720.
56. Li, J, Norgard, B, Precht, DH, Olsen, J. Psychological stress and inflammatory bowel disease: a follow-up study in parents who lost a child in Denmark. Am J Gastroenterol 2004;99:11291133.
57. Goldsmith, DR, Rapaport, MH, Miller, BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry 2016;21:16961709.
58. Margaretten, M, Julian, L, Katz, P, Yelin, E. Depression in patients with rheumatoid arthritis: description, causes and mechanisms. Int J Clin Rheumatol 2011;6:617623.
59. Tyring, S, Gottlieb, A, Papp, K et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 2006;367:2935.
60. Hare, DL, Toukhsati, SR, Johansson, P, Jaarsma, T. Depression and cardiovascular disease: a clinical review. Eur Heart J 2014;35:13651372.
61. Andreoulakis, E, Hyphantis, T, Kandylis, D, Iacovides, A. Depression in diabetes mellitus: a comprehensive review. Hippokratia 2012;16:205214.
62. Bonaccorso, S, Marino, V, Biondi, M, Grimaldi, F, Ippoliti, F, Maes, M. Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. J Affect Disord 2002;72:237241.
63. Capuron, L, Ravaud, A, Dantzer, R. Early depressive symptoms in cancer patients receiving interleukin 2 and/or interferon alfa-2b therapy. J Clin Oncol 2000;18:21432151.
64. Grigoleit, J-S, Kullmann, JS, Wolf, OT et al. Dose-dependent effects of endotoxin on neurobehavioral functions in humans. PloS One 2011;6:e28330.
65. Reichenberg, A, Yirmiya, R, Schuld, A et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 2001;58:445452.
66. Kent, S, Bluthe, RM, Kelley, KW, Dantzer, R. Sickness behavior as a new target for drug development. Trends Pharmacol Sci 1992;13:2428.
67. Eisenberger, NI, Inagaki, TK, Mashal, NM, Irwin, MR. Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav Immun 2010;24:558563.
68. Maes, M, Berk, M, Goehler, L et al. Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med 2012;10:66.
69. Zhu, H, Li, YR. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med (Maywood) 2012;237:474480.
70. Maes, M, Kubera, M, Obuchowiczwa, E, Goehler, L, Brzeszcz, J. Depression’s multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways. Neuro Endocrinol Lett 2011;32:724.
71. Köhler, O, Benros, ME, Nordentoft, M et al. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 2014;71:13811391.
72. Ennaifer, R, Elleuch, N, Cheikh, M et al. Risk factors of psychological disorders in inflammatory bowel disease in a tunisian survey. Results of a cross-sectional study. Tuni Med 2014;92:723726.
73. Nahon, S, Lahmek, P, Durance, C et al. Risk factors of anxiety and depression in inflammatory bowel disease. Inflamm Bowel Dis 2012;18:20862091.
74. Sainsbury, A, Heatley, RV. Review article: psychosocial factors in the quality of life of patients with inflammatory bowel disease. Aliment Pharmacol Ther 2005;21:499508.
75. Zelinkova, Z, der Woude, C. Gender and inflammatory bowel disease. J Clin Cell Immunol 2014;5:245–253.
76. Panara, AJ, Yarur, AJ, Rieders, B et al. The incidence and risk factors for developing depression after being diagnosed with inflammatory bowel disease: a cohort study. Aliment Pharmacol Ther 2014;39:802810.
77. Casellas, F, Lopez-Vivancos, J, Casado, A, Malagelada, JR. Factors affecting health related quality of life of patients with inflammatory bowel disease. Qual Life Res 2002;11:775781.
78. Hauser, G, Tkalčić, M, Stimac, D, Milic, S, Sincic, BM. Gender related differences in quality of life and affective status in patients with inflammatory bowel disease. Coll Antropol 2011;35(Suppl. 2):203207.
79. Berrill, JW, Green, JT, Hood, K, Campbell, AK. Symptoms of irritable bowel syndrome in patients with inflammatory bowel disease: examining the role of sub-clinical inflammation and the impact on clinical assessment of disease activity. Aliment Pharmacol Ther 2013;38:4451.
80. Norton, C, Czuber-Dochan, W, Bassett, P et al. Assessing fatigue in inflammatory bowel disease: comparison of three fatigue scales. Aliment Pharmacol Ther 2015;42:203211.
81. Lima, FD, Ribeiro, TC, Chebli, LA et al. Mood swings in patients with Crohn’s disease: incidence and associated factors. Rev Assoc Med Bras (1992) 2012;58:481488.
82. Hou, JK, Abraham, B, El-Serag, H. Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol 2011;106:563–573.
83. Olendzki, BC, Silverstein, TD, Persuitte, GM, Ma, Y, Baldwin, KR, Cave, D. An anti-inflammatory diet as treatment for inflammatory bowel disease: a case series report. Nutr J 2014;13:5.
84. Deberry, JJ, Bielefeldt, K, Davis, BM, Szigethy, EM, Hartman, DJ, Coates, MD. Abdominal pain and the neurotrophic system in ulcerative colitis. Inflamm Bowel Dis 2014;20:23302339.
85. Srinath, AI, Goyal, A, Zimmerman, LA et al. Predictors of abdominal pain in depressed pediatric inflammatory bowel disease patients. Inflamm Bowel Dis 2014;20:13291340.
86. Goyal, N, Rana, A, Ahlawat, A, Bijjem, KR, Kumar, P. Animal models of inflammatory bowel disease: a review. Inflammopharmacology 2014;22:219233.
87. Okayasu, I, Hatakeyama, S, Yamada, M, Ohkusa, T, Inagaki, Y, Nakaya, R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 1990;98:694702.
88. Gaudio, E, Taddei, G, Vetuschi, A et al. Dextran sulfate sodium (DSS) colitis in rats: clinical, structural, and ultrastructural aspects. Dig Dis Sci 1999;44:14581475.
89. Morris, GP, Beck, PL, Herridge, MS, Depew, WT, Szewczuk, MR, Wallace, JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989;96:795803.
90. Bouma, G, Strober, W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 2003;3:521533.
91. Nell, S, Suerbaum, S, Josenhans, C. The impact of the microbiota on the pathogenesis of IBD: lessons from mouse infection models. Nat Rev Microbiol 2010;8:564577.
92. Mansfield, LS, Bell, JA, Wilson, DL et al. C57BL/6 and congenic interleukin-10-deficient mice can serve as models of Campylobacter jejuni colonization and enteritis. Infect Immun 2007;75:10991115.
93. O’Mahony, SM, Hyland, NP, Dinan, TG, Cryan, JF. Maternal separation as a model of brain-gut axis dysfunction. Psychopharmacology 2011;214:7188.
94. Reber, SO, Birkeneder, L, Veenema, AH et al. Adrenal insufficiency and colonic inflammation after a novel chronic psycho-social stress paradigm in mice: implications and mechanisms. Endocrinology 2007;148:670682.
95. Reber, SO, Obermeier, F, Straub, RH, Veenema, AH, Neumann, ID. Aggravation of DSS-induced colitis after chronic subordinate colony (CSC) housing is partially mediated by adrenal mechanisms. Stress 2008;11:225234.
96. Vicario, M, Guilarte, M, Alonso, C et al. Chronological assessment of mast cell-mediated gut dysfunction and mucosal inflammation in a rat model of chronic psychosocial stress. Brain Behav Immun 2010;24:11661175.
97. Heydarpour, P, Rahimian, R, Fakhfouri, G et al. Behavioral despair associated with a mouse model of Crohn’s disease: role of nitric oxide pathway. Prog Neuropsychopharmacol Biol Psychiatry 2016;64:131141.
98. Chen, J, Winston, JH, Fu, Y et al. Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation. Am J Physiol Regul Integr Comp Physiol 2015;308:R18R27.
99. Messaoudi, M, Desor, D, Grasmuck, V, Joyeux, M, Langlois, A, Roman, FJ. Behavioral evaluation of visceral pain in a rat model of colonic inflammation. Neuroreport 1999;10:11371141.
100. Painsipp, E, Herzog, H, Sperk, G, Holzer, P. Sex-dependent control of murine emotional-affective behaviour in health and colitis by peptide YY and neuropeptide Y. Br J Pharmacol 2011;163:13021314.
101. Lyte, M, Li, W, Opitz, N, Gaykema, RP, Goehler, LE. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium . Physiol Behav 2006;89:350357.
102. Gareau, MG, Wine, E, Rodrigues, DM et al. Bacterial infection causes stress-induced memory dysfunction in mice. Gut 2011;60:307317.
103. Emge, JR, Huynh, K, Miller, EN et al. Modulation of the microbiota-gut-brain axis by probiotics in a murine model of inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2016;310:G989G998.
104. Bercik, P, Park, AJ, Sinclair, D et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil 2011;23:11321139.
105. Frenois, F, Moreau, M, O’Connor, J et al. Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior. Psychoneuroendocrinology 2007;32:516531.
106. Mayhan, WG, Arrick, DM. eds. The Blood-Brain Barrier in Health and Disease. Colloquium Series on Integrated Systems Physiology: From Molecule to Function to Disease. Morgan & Claypool Life Sciences, San Rafael, CA, USA, 2016.
107. Varatharaj, A, Galea, I. The blood-brain barrier in systemic inflammation. Brain Behav Immun 2017;60:112.
108. Hathaway, CA, Appleyard, CB, Percy, WH, Williams, JL. Experimental colitis increases blood-brain barrier permeability in rabbits. Am J Physiol 1999;276(Pt 1):G1174G1180.
109. Hathaway, CA, Percy, WH, Williams, JL. Effects of free radicals and leukocytes on increases in blood-brain barrier permeability during colitis. Dig Dis Sci 2000;45:967975.
110. Natah, SS, Mouihate, A, Pittman, QJ, Sharkey, KA. Disruption of the blood-brain barrier during TNBS colitis. Neurogastroenterol Motil 2005;17:433446.
111. Sans, M, Kawachi, S, Soriano, A et al. Brain endothelial adhesion molecule expression in experimental colitis. Microcirculation 2001;8:105114.
112. Neurath, MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014;14:329342.
113. Leonard, B, Maes, M. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 2012;36:764785.
114. Riazi, K, Galic, MA, Kuzmiski, JB, Ho, W, Sharkey, KA, Pittman, QJ. Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation. Proc Natl Acad Sci USA 2008;105:1715117156.
115. Medhi, B, Prakash, A, Avti, PK, Chakrabarti, A, Khanduja, KL. Intestinal inflammation and seizure susceptibility: understanding the role of tumour necrosis factor-alpha in a rat model. J Pharm Pharmacol 2009;61:13591364.
116. Wang, K, Yuan, CP, Wang, W et al. Expression of interleukin 6 in brain and colon of rats with TNBS-induced colitis. World J Gastroenterol 2010;16:22522259.
117. Baticic, L, Detel, D, Kucic, N, Buljevic, S, Pugel, EP, Varljen, J. Neuroimmunomodulative properties of dipeptidyl peptidase IV/CD26 in a TNBS-induced model of colitis in mice. J Cell Biochem 2011;112:33223333.
118. Alhouayek, M, Lambert, DM, Delzenne, NM, Cani, PD, Muccioli, GG. Increasing endogenous 2-arachidonoylglycerol levels counteracts colitis and related systemic inflammation. FASEB J 2011;25:27112721.
119. Villaran, RF, Espinosa-Oliva, AM, Sarmiento, M et al. Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson’s disease. J Neurochem 2010;114:16871700.
120. Reichmann, F, Hassan, AM, Farzi, A, Jain, P, Schuligoi, R, Holzer, P. Dextran sulfate sodium-induced colitis alters stress-associated behaviour and neuropeptide gene expression in the amygdala-hippocampus network of mice. Sci Rep 2015;5:9970.
121. Becher, B, Spath, S, Goverman, J. Cytokine networks in neuroinflammation. Nat Rev Immunol 2017;17:4959.
122. Hanisch, UK. Microglia as a source and target of cytokines. Glia 2002;40:140155.
123. Sofroniew, MV. Multiple roles for astrocytes as effectors of cytokines and inflammatory mediators. Neuroscientist 2014;20:160172.
124. Dantzer, R, O’Connor, JC, Freund, GG, Johnson, RW, Kelley, KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008;9:4656.
125. Khairova, RA, Machado-Vieira, R, Du, J, Manji, HK. A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol 2009;12:561578.
126. Stellwagen, D, Malenka, RC. Synaptic scaling mediated by glial TNF-alpha. Nature 2006;440:10541059.
127. Miller, AH, Haroon, E, Raison, CL, Felger, JC. Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress Anxiety 2013;30:297306.
128. O’Connor, JC, Andre, C, Wang, Y et al. Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. J Neurosci 2009;29:42004209.
129. Dunn, AJ. Cytokine activation of the HPA axis. Ann N Y Acad Sci 2000;917:608617.
130. Miller, AH, Pariante, CM, Pearce, BD. Effects of cytokines on glucocorticoid receptor expression and function. Glucocorticoid resistance and relevance to depression. Adv Exp Med Biol 1999;461:107116.
131. Pariante, CM, Lightman, SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci 2008;31:464468.
132. Kim, YK, Na, KS, Myint, AM, Leonard, BE. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2016;64:277284.
133. Kovacs, KJ. Measurement of immediate-early gene activation- c-fos and beyond. J Neuroendocrinol 2008;20:665672.
134. Okuno, H. Regulation and function of immediate-early genes in the brain: beyond neuronal activity markers. Neurosci Res 2011;69:175186.
135. Miampamba, M, Sharkey, KA. c-Fos expression in the myenteric plexus, spinal cord and brainstem following injection of formalin in the rat colonic wall. J Auton Nerv Sys 1999;77:140151.
136. Porcher, C, Sinniger, V, Juhem, A, Mouchet, P, Bonaz, B. Neuronal activity and CRF receptor gene transcription in the brains of rats with colitis. Am J Physiol Gastrointest Liver Physiol 2004;287:G803G814.
137. Hsiao, EY. Gastrointestinal issues in autism spectrum disorder. Harv Rev Psychiatry 2014;22:104111.
138. Welch, MG, Welch-Horan, TB, Anwar, M, Anwar, N, Ludwig, RJ, Ruggiero, DA. Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin. J Mol Neurosci 2005;25:259274.
139. Welch, MG, Anwar, M, Chang, CY et al. Combined administration of secretin and oxytocin inhibits chronic colitis and associated activation of forebrain neurons. Neurogastroenterol Motil 2010;22:654e202.
140. Goehler, LE, Gaykema, RP, Opitz, N, Reddaway, R, Badr, N, Lyte, M. Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni . Brain Behav Immun 2005;19:334344.
141. Dave, M, Higgins, PD, Middha, S, Rioux, KP. The human gut microbiome: current knowledge, challenges, and future directions. Transl Res 2012;160:246257.
142. Frank, DN, St Amand, AL, Feldman, RA, Boedeker, EC, Harpaz, N, Pace, NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 2007;104:1378013785.
143. Jandhyala, SM, Talukdar, R, Subramanyam, C, Vuyyuru, H, Sasikala, M, Reddy, DN. Role of the normal gut microbiota. World J Gastroenterol 2015;21:87878803.
144. Jostins, L, Ripke, S, Weersma, RK et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012;491:119124.
145. Nitzan, O, Elias, M, Peretz, A, Saliba, W. Role of antibiotics for treatment of inflammatory bowel disease. World J Gastroenterol 2016;22:10781087.
146. Sellon, RK, Tonkonogy, S, Schultz, M et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun 1998;66:52245231.
147. Sherwin, E, Sandhu, KV, Dinan, TG, Cryan, JF. May the force be with you: the light and dark sides of the microbiota-gut-brain axis in neuropsychiatry. CNS Drugs 2016;30:1019–1041.
148. Fuller, R. Probiotics: the scientific basis. Gut 1993;34:863864.
149. Gibson, GR, Roberfroid, MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 1995;125:14011412.
150. Mallon, P, McKay, D, Kirk, S, Gardiner, K. Probiotics for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2007;4:Cd005573.
151. Rahimi, R, Nikfar, S, Rahimi, F et al. A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in Crohn’s disease. Dig Dis Sci 2008;53:25242531.
152. Casellas, F, Borruel, N, Torrejon, A et al. Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin. Aliment Pharmacol Ther 2007;25:10611067.
153. Bamba, T, Kanauchi, O, Andoh, A, Fujiyama, Y. A new prebiotic from germinated barley for nutraceutical treatment of ulcerative colitis. J Gastroenterol Hepatol 2002;17:818824.
154. Kanauchi, O, Suga, T, Tochihara, M et al. Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial. J Gastroenterol 2002;37(Suppl. 14):6772.
155. Benjamin, JL, Hedin, CR, Koutsoumpas, A et al. Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn’s disease. Gut 2011;60:923929.
156. Lindsay, JO, Whelan, K, Stagg, AJ et al. Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn’s disease. Gut 2006;55:348355.
157. Messaoudi, M, Lalonde, R, Violle, N et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 2011;105:755764.
158. Rao, AV, Bested, AC, Beaulne, TM et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog 2009;1:6.
159. Schmidt, K, Cowen, PJ, Harmer, CJ, Tzortzis, G, Errington, S, Burnet, PW. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology 2015;232:17931801.
160. Colman, RJ, Rubin, DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis 2014;8:15691581.
161. Moayyedi, P, Surette, MG, Kim, PT et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 2015;149:102109.e6.
162. Rossen, NG, Fuentes, S, van der Spek, MJ et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 2015;149:110118.e4.
163. Kelly, JR, Borre, Y, O’Brien, C, Patterson, E et al. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res 2016;82:109118.
164. Heijtz, RD, Wang, S, Anuar, F et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA 2011;108:30473052.
165. Bercik, P, Park, AJ, Sinclair, D, Khoshdel, A, Lu, J, Huang, X. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil 2011;23:1132–1139.
166. Goehler, LE, Park, SM, Opitz, N, Lyte, M, Gaykema, RP. Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain Behav Immun 2008;22:354366.
167. Bravo, JA, Forsythe, P, Chew, MV et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA 2011;108:1605016055.
168. Desbonnet, L, Garrett, L, Clarke, G, Kiely, B, Cryan, JF, Dinan, TG. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 2010;170:11791188.
169. Zonis, S, Pechnick, RN, Ljubimov, VA et al. Chronic intestinal inflammation alters hippocampal neurogenesis. J Neuroinflammation 2015;12:112.
170. Konturek, PC, Brzozowski, T, Konturek, SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol 2011;62:591599.
171. Deng, Q, Chen, H, Liu, Y et al. Psychological stress promotes neutrophil infiltration in colon tissue through adrenergic signaling in DSS-induced colitis model. Brain Behav Immun. 2016;30:243–254.
172. Wood, JD, Peck, OC, Tefend, KS et al. Evidence that colitis is initiated by environmental stress and sustained by fecal factors in the cotton-top tamarin (Saguinus oedipus). Dig Dis Sci 2000;45:385393.
173. Milde, AM, Murison, R. A study of the effects of restraint stress on colitis induced by dextran sulphate sodium in singly housed rats. Integr Physiol Behav Sci 2002;37:140150.
174. Milde, AM, Arslan, G, Overmier, JB, Berstad, A, Murison, R. An acute stressor enhances sensitivity to a chemical irritant and increases 51CrEDTA permeability of the colon in adult rats. Integr Physiol Behav Sci 2005;40:3544.
175. Peters, S, Grunwald, N, Rummele, P et al. Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice. Stress 2012;15:403415.
176. Greenwood-Van Meerveld, B, Johnson, AC, Schulkin, J, Myers, DA. Long-term expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus in response to an acute colonic inflammation. Brain Res 2006;1071:9196.
177. Kojima, K, Naruse, Y, Iijima, N et al. HPA-axis responses during experimental colitis in the rat. Am J Physiol Regul Integr Comp Physiol 2002;282:R1348R1355.
178. Agostini, A, Filippini, N, Cevolani, D et al. Brain functional changes in patients with ulcerative colitis: a functional magnetic resonance imaging study on emotional processing. Inflamm Bowel Dis 2011;17:17691777.
179. Agostini, A, Filippini, N, Benuzzi, F et al. Functional magnetic resonance imaging study reveals differences in the habituation to psychological stress in patients with Crohn’s disease versus healthy controls. J Behav Med 2013;36:477487.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
  • URL: /core/journals/acta-neuropsychiatrica
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed