Psychoneuroendocrine:  Research Article

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Peptic Ulcer and Inflammatory Bowel Disease

CITATION: Susan Levenstein. (2002). Psychosocial Factors in Peptic Ulcer and Inflammatory Bowel Disease. Journal of Consulting and Clinical Psychology.  June 2002, Vol. 70, No. 3, p 739-750.

Over the past decade, while gastroenterologists' interest in mind-body interactions in organic disorders dwindled, stronger evidence has linked psychosocial factors with the incidence and recurrence of peptic ulcer and with the course of inflammatory bowel disease. Psychological-behavioral approaches to treatment continue to be disappointing. Psychosocial factors may affect ulcer by increasing duodenal acid load, altering local circulation or motility, intensifying Helicobacter pylori infection, stimulating corticosteroid secretion, and affecting health risk behaviors; possible mechanisms for inflammatory bowel disease include immune deregulation, gut permeability changes, and poor medication adherence. Both belong to the growing category of diseases thought to have an infectious component: for peptic ulcer the bacterium Helicobacter pylori, for inflammatory bowel disease an exaggerated immune response to gut bacteria. Peptic ulcer and inflammatory bowel disease, which present unique interactions among psychological, immunologic, endocrine, infectious, and behavioral factors, are splendid paradigms of the biopsychosocial model. 


1. Adami, H. O., Bergström, R., Nyren, O., Forhaug, K., Gustravsson, S., Lööf, L. & Nyberg, A. (1987). Is duodenal ulcer really a psychosomatic disease? A population-based case-control study. Scandinavian Journal of Gastroenterology, 22, 889-896. 

2. Ader, R., Felten, D. L. & Cohen, N. (1991). Psychoneuroimmunolog y. (2nd ed.). San Diego, CA: Academic Press.

3. Alexander, F. & French, T. M. (1948). Studies in psychosomatic medicine. New York: Ronald Press.

4. Anda, R. F., Williamson, D. F., Escobedo, L. G., Remington, P. L., Mast, E. E. & Madans, J. H. (1992). Self-perceived stress and the risk of peptic ulcer disease: A longitudinal study of US adults. Archives of Internal Medicine, 152, 829-833.

5. Aoyama, N., Kinoshita, Y., Fujimoto, S., Himeno, S., Todo, A., Kasuga, M. & Chiba, T. (1998). Peptic ulcers after the Hanshin-Awaji earthquake: Increased incidence of bleeding gastric ulcers. American Journal of Gastroenterology, 93, 311-316.

6. Armstrong, D., Arnold, R., Classen, M., Fischer, M., Goebell, H., Schepp, W. & Blum, A. L. (1994). RUDER—A prospective, two-year, multicenter study of risk factors for duodenal ulcer relapse during maintenance therapy with ranitidine. Digestive Diseases and Sciences, 39, 1425-1433. 

7. Aronowitz, R. & Spiro, H. M. (1988). The rise and fall of the psychosomatic hypothesis in ulcerative colitis. Journal of Clinical Gastroenterology, 10, 298-305.

8. Bank, L., Wright, J. P., Lucke, W. & Marks, I. N. (1986). Peptic ulcer: A follow-up study. Journal of Clinical Gastroenterology, 8, 381-384. 

9. Barsky, A. J. (1992). Amplification, somatization, and the somatoform disorders. Psychosomatics, 33, 28-34.

10. Bayless, T. M. & Harris, M. L. (1990). Inflammatory bowel disease and irritable bowel syndrome. Medical Clinics of North America, 74, 21-29. 

11. Bennett, E., Beaurepaire, J., Langeluddecke, P., Kellow, J. & Tennant, C. (1991). Life stress and non-ulcer dyspepsia: A case-control study. Journal of Psychosomatic Research, 35, 579-590.

12. Blumberg, R. & Strober, W. (2001). Prospects for research in inflammatory bowel disease. Journal of the American Medical Association, 285, 643-647. 

13. Bresnick, W. H., Rask-Madsen, C., Hogan, D. L., Koss, M. A. & Isenberg, J. I. (1993). The effect of acute emotional stress on gastric acid secretion in normal subjects and duodenal ulcer patients. Journal of Clinical Gastroenterology, 17, 117-122.

14. Brown, G. W. & Harris, T. O. (1978). Social origins of depression: A study of psychiatric disorder in women. London: Tavistock.

15. Calkins, B. M. (1989). A meta-analysis of the role of smoking in inflammatory bowel disease. Digestive Diseases and Sciences, 34, 1841-1854. 

16. Campieri, M. & Gionchetti, P. (2001). Bacteria as the cause of ulcerative colitis. Gut, 48, 132-135. 

17. Chan, F. K., Sung, J. J., Lee, Y. T., Leung, W. K., Chan, L. Y., Yung, M. Y. & Chung, S. C. (1997). Does smoking predispose to peptic ulcer relapse after eradication of Helicobacter pylori. American Journal of Gastroenterology, 92, 442-445. 

18. Ciociola, A. A., McSorley, D. J., Turner, K., Sykes, D. & Palmer, J. B. (1999). Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated. American Journal of Gastroenterology, 94, 1834-1840. 

19. Cohen, S., Tyrrell, D. A. J. & Smith, A. P. (1991). Psychological stress and susceptibility to the common cold. New England Journal of Medicine, 325, 606-612.

20. Collins, S. M., McHugh, K., Jacobson, K., Khan, I., Riddell, R., Murase, K. & Weingarten, H. P. (1996). Previous inflammation alters the response of the rat colon to stress. Gastroenterology, 111, 1509-1515.

21. Craig, T. K. J. & Brown, G. W. (1984). Goal frustration and life events in the aetiology of painful gastrointestinal disorder. Journal of Psychosomatic Research, 28, 411-421.

22. Creed, F. (1981). Life events and appendectomy. Lancet, 1381-1385.

23. Creed, F. & Guthrie, E. (1991). Relation among personality and symptoms in nonulcer dyspepsia and the irritable bowel syndrome. Gastroenterology, 100, 1154-1155. 

24. Daniels, G. E. (1944). Nonspecific ulcerative colitis as a psychosomatic disease. Medical Clinics of North America, 28, 593-602. 

25. Dhabhar, F. S. & McEwen, B. S. (1996). Stress-induced enhancement of antigen-specific cell-mediated immunity. Journal of Immunology, 156, 2608-2615.

26. D'Haens, G., Van Deventer, S., Van Hogezand, R., Chalmers, D., Kothe, C., Baert, F., Braakman, T., Schaible, T., Geboes, K. & Rutgeerts, P. (1999). Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial. Gastroenterology, 116, 1029-1034. 

27. Dinan, T. G., O'Keane, V., O'Boyle, C., Chua, A. & Keeling, P. W. N. (1991). A comparison of the mental status, personality profiles and life events of patients with irritable bowel syndrome and peptic ulcer disease. Acta Psychiatrica Scandinavica, 84, 26-28.

28. Duffy, L. C., Zielezny, M. A., Marshall, J. R., Weiser, M. M., Phillips, J. F., Byers, T. E., Calkins, B. M., Graham, S. & Ogra, P. L. (1991). Lag time between stress events and risk of recurrent episodes of inflammatory bowel disease. Epidemiology, 2, 141-145.

29. Ellard, K., Beaurepaire, J., Jones, M., Piper, D. & Tennant, C. (1990). Acute and chronic stress in duodenal ulcer disease. Gastroenterology, 99, 1628-1632.
Cited by 5 

30. Esler, M. D. & Goulston, K. J. (1973). Levels of anxiety in colonic disorders. New England Journal of Medicine, 288, 16-20.

31. (1993). Epidemiology of, and risk factors for, Helicobacter pylori infection among 3194 asymptomatic subjects in 17 populations. Gut, 34, 1672-1676. 

32. Fava, G. A. & Pavan, L. (1976). Large bowel disorders: I. Illness configuration and life events. Psychotherapy and Psychosomatics, 27, 93-99.

33. Fava, G. A. & Pavan, L. (1976). Large bowel disorders: II. Psychopathology and alexithymia. Psychotherapy and Psychosomatics, 27, 100-105.

34. Feldman, F., Cantor, D., Soll, S. & Bachrach, W. (1967). Psychiatric study of a consecutive series of 34 patients with ulcerative colitis. British Medical Journal, 3, 14-19 (No. 556).

35. Feldman, M., Walker, P., Goldschmiedt, M. & Cannon, D. (1992). Role of affect and personality in gastric acid secretion and serum gastrin concentration: Comparative studies in normal men and in male duodenal ulcer patients. Gastroenterology, 102, 175-180. 

36. Fordtran, J. S. & Walsh, J. H. (1973). Gastric acid secretion rate and buffer content of the stomach after eating: Results in normal subjects and in patients with duodenal ulcer. Journal of Clinical Investigation, 52, 645-657. 

37. Fraser, A. G., Schreuder, V., Chua, L. E. & Moore, L. (1998). Follow up after successful eradication of Helicobacter pylori: Symptoms and reinfection. Journal of Gastroenterology and Hepatology, 13, 555-559. 

38. Friedman, G. D., Siegelaub, A. B. & Seltzer, C. S. (1974). Cigarettes, alcohol, coffee and peptic ulcer. New England Journal of Medicine, 290, 469-473.

39. Gazzard, B. G., Price, H. L., Libby, G. W. & Dawson, A. M. (1978). The social toll of Crohn's disease. British Medical Journal, 2, 1117-1119.

40. Glaser, R., Pearson, G. R., Bonneau, R. H., Esterling, B. A., Atkinson, C. & Kiecolt-Glaser, J. K. (1993). Stress and the memory T-cell response to the Epstein-Barr virus in healthy medical students. Health Psychology, 12, 435-442.

41. Gold, N., Issenman, R., Roberts, J. & Watt, S. (2000). Well-adjusted children: An alternate view of children with inflammatory bowel disease and functional gastrointestinal complaints. Inflammatory Bowel Diseases, 6, 1-7.

42. Goulston, K. J., Dent, O. F. & Chapuis, P. H. (1995). Gastrointestinal morbidity among World War II prisoners of war: 40 years on. Medical Journal of Australia, 143, 6-10. 

43. Graham, D. Y., Malaty, H. M., Evans, D. G., Evans, D. J., Klein, P. D. & Adam, E. (1991). Epidemiology of Helicobacter pylori in an asymptomatic population in the U.S.: Effect of age, race, and socioeconomic status. Gastroenterology, 100, 1495-1501. 

44. Graham, D. Y. & Osato, M. S. (2000). Helicobacter pylori in the pathogenesis of duodenal ulcer: Interaction between duodenal acid load, bile, and H. pylori. American Journal of Gastroenterology, 95, 87-91. 

45. Greene, B. R., Blanchard, E. B. & Wan, C. K. (1994). Long-term monitoring of psychosocial stress and symptomatology in inflammatory bowel disease. Behaviour Research and Therapy, 32, 217-226.

46. Greenfield, C., Aguilar Ramirez, J. R., Pounder, R. E., Williams, T., Danvers, M., Marper, S. R. & Noone, P. (1983). Clostridium difficile and inflammatory bowel disease. Gut, 24, 713-717. 

47. Guthrie, E., Creed, F., Dawson, D. & Tomenson, B. (1991). A controlled trial of psychological treatment for the irritable bowel syndrome. Gastroenterology, 100, 450-457.

48. Gwee, K. A., Leong, Y. L., Graham, J. C., McKendrick, M. W., Collins, S. M., Walters, S. J. & Read, N. W. (1999). The role of psychological and biological factors in post infective gut dysfunction. Gut, 44, 400-406.

49. Haug, T. T., Svebak, S., Wilhelmsen, I., Berstad, A. & Ursin, H. (1994). Psychological factors and somatic symptoms in functional dyspepsia. A comparison with duodenal ulcer and healthy controls. Journal of Psychosomatic Research, 38, 281-291.

50. Hausken, T., Svebak, S., Wilhelmsen, I., Tangen, T., Olafsen, K., Pettersson, E., Hveem, K. & Berstad, A. (1993). Low vagal tone and antral dysmotility in patients with functional dyspepsia. Psychosomatic Medicine, 55, 12-22.

51. Helzer, J. E., Stillings, W. A., Chammas, S., Norland, C. C. & Alpers, D. H. (1982). A controlled study of the association between ulcerative colitis and psychiatric diagnosis. Digestive Diseases and Sciences, 27, 513-518.

52. Hendriksen, C. & Binder, V. (1980). Social prognosis in patients with ulcerative colitis. British Medical Journal, 281, 581-583.

53. Hislop, I. G. (1974). Onset setting in inflammatory bowel disease. Medical Journal of Australia, 1, 981-984. 

54. Hojgaard, L. & Bendtsen, F. (1989). Gastric potential difference and pH in ulcer patients and normal volunteers during Stroop's colour word conflict test. Gut, 30, 782-785. 

55. Hollander, D., Vadheim, C. M., Brettholz, E., Peterson, G. M., Delahunty, T. & Rotter, J. I. (1986). Increased intestinal permeability in patients with Crohn's disease and their relatives: A possible etiologic factor. Annals of Internal Medicine, 105, 883-885. 

56. Holtmann, G., Armstrong, D., Pöppel, E., Bauerfeind, A., Goebell, H., Arnold, R., Classen, M., Witzel, L., Fischer, M., Heinisch, M. & Blum, A. L. (1992). Influence of stress on the healing and relapse of duodenal ulcers. Scandinavian Journal of Gastroenterology, 27, 917-923.

57. Hook-Nikanne, J., Sistonen, P. & Kosunen, T. U. (1990). Effect of ABO blood group and secretor status on the frequency of Helicobacter pylori antibodies. Scandinavian Journal of Gastroenterology, 25, 814-818. 

58. Jantschek, G., Zeitz, M., Pritsch, M., Wirsching, M., Klor, H. U., Studt, H. H., Rasenack, J., Deter, H. C., Riecken, E. O., Feiereis, H. & Keller, W. (1998). Effect of psychotherapy on the course of Crohn's disease. Results of the German prospective multicenter psychotherapy treatment study on Crohn's disease. German Study Group on Psychosocial Intervention in Crohn's Disease. Scandinavian Journal of Gastroenterology, 33, 1289-1296.

59. Jess, P. (1994). Gastric acid secretion in relation to personality, affect and coping ability in duodenal ulcer patients. A multivariate analysis. Danish Medical Bulletin, 41, 100-103 Hvidovre Ulcer Project Group.

60. Jess, P. (1994). Personality pattern in peptic ulcer disease: A cohort study. Journal of Internal Medicine, 236, 271-274.

61. Jess, P. & Eldrup, J. (1994). The personality patterns in patients with duodenal ulcer and ulcer-like dyspepsia and their relationship to the course of the diseases. Journal of Internal Medicine, 235, 589-594 Hvidovre Ulcer Project Group.

62. Jess, P., Lieth, L. V. D., Matzen, P., Madsen, P., Krag, E., Knigg, U., Hojgaard, L., Dejgard, A., Christiansen, P. M. & Bonnevie, O. (1989). The personality pattern of duodenal ulcer patients in relation to spontaneous ulcer healing and relapse. Journal of Internal Medicine, 226, 395-400. 

63. Jorgensen, J., Ranlov, P. J., Bjerrum, P. J., Diemer, H., Bisgaard, K. & Elsborg, L. (2001). Is an increased intestinal permeability a valid predictor of relapse in Crohn disease. Scandinavian Journal of Gastroenterology, 36, 521-527 (Suppl. 5). 

64. Kauffman, G. L. (1997). Stress, the brain, and the gastric mucosa. American Journal of Surgery, 174, 271-275. 

65. Kawahito, Y., Sano, H., Mukai, S., Asai, K., Kimura, S., Yamamura, Y., Kato, H., Chrousos, G. P., Wilder, R. L. & Kondo, M. (1995). Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis. Gut, 37, 544-551.

66. Kiecolt-Glaser, J. K., Glaser, R., Gravenstein, S., Malarkey, W. B. & Sheridan, J. (1996). Chronic stress alters the immune response to influenza virus vaccine in older adults. Proceedings of the National Academy of Sciences, USA, 93, 3043-3047.

67. Kiss, A., Nemeskeri, N., Maritesch, F., Vogelsang, H., Ferenci, P., Sedlmayer, A., Vogelsang, H., Ferenci, P., Sedlmayer, A., Langewitz, W. & Gangl, A. (1991). Stressful life events and acute relapse of Crohn's disease [Abstract] . Psychosomatic Medicine, 53, 215. 

68. Kurata, J. H., Nogawa, A. N., Abbey, D. E. & Petersen, F. (1992). A prospective study of risk for peptic ulcer disease in Seventh-Day Adventists. Gastroenterology, 102, 902-909. 

69. Lagergren, J., Bergstrom, R., Lindgren, A. & Nyren, O. (1999). Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. New England Journal of Medicine, 340, 825-831.

70. Lam, S. K., Hui, W. M., Shiu, L. P. & Ng, M. M. (1995). Society stress and peptic ulcer perforation. Journal of Gastroenterology and Hepatology, 10, 570-576.

71. Langeluddeck, P., Goulston, K. & Tennant, C. (1990). Psychological factors in dyspepsia of unknown cause: A comparison with peptic ulcer disease. Journal of Psychosomatic Research, 34, 214-222. 

72. LeClere, F. B., Moss, A. J., Everhart, J. E. & Roth, H. P. (1992). Prevalence of major digestive disorders and bowel symptoms, 1989. Advance Data From Vital and Health Statistics of the National Center for Health Statistics, 212, 1-16. 

73. Leoci, C., Ierardi, E., Chiloiro, M., Piccioli, E., Di Matteo, G., Misciagna, G. & Giorgio, I. (1995). Incidence and risk factors of duodenal ulcer. Journal of Clinical Gastroenterology, 20, 104-109 A retrospective cohort study. 

74. Levenstein, S. (1998). Stress and peptic ulcer: Life beyond Helicobacter. British Medical Journal, 316, 538-541.

75. Levenstein, S. (2000). The very model of a modern etiology: A biopsychosocial view of peptic ulcer. Psychosomatic Medicine, 62, 176-185.

76. Levenstein, S. & Kaplan, G. A. (1998). Socioeconomic status and ulcer: A prospective study of contributory risk factors. Journal of Clinical Gastroenterology, 26, 14-17.

77. Levenstein, S., Kaplan, G. A. & Smith, M. (1995). Sociodemographic characteristics, life stressors, and peptic ulcer: A prospective study. Journal of Clinical Gastroenterology, 21, 185-192.

78. Levenstein, S., Kaplan, G. A. & Smith, M. W. (1997). Psychological predictors of peptic ulcer incidence in the Alameda County Study. Journal of Clinical Gastroenterology, 24, 140-146.

79. Levenstein, S., Prantera, C., Scribano, M. L., Varvo, V., Berto, E. & Spinella, S. (1996). Psychologic predictors of duodenal ulcer healing. Journal of Clinical Gastroenterology, 22, 84-89.

80. Levenstein, S., Prantera, C., Varvo, V., Arcà, M., Scribano, M. L., Spinella, S. & Berto, E. (1996). Long-term symptom patterns in duodenal ulcer: Psychosocial factors. Journal of Psychosomatic Research, 41, 465-472.

81. Levenstein, S., Prantera, C., Varvo, V., Scribano, M. L., Andreoli, A., Luzi, C., Arcà, M., Berto, E., Milite, G. & Marcheggiano, A. (2000). Stress and exacerbation in ulcerative colitis: A prospective study of patients enrolled in remission. American Journal of Gastroenterology, 95, 1213-1220.

82. Levenstein, S., Prantera, C., Varvo, V., Scribano, M. L., Berto, E., Andreoli, A. & Luzi, C. (1994). Psychological stress and disease activity in ulcerative colitis: A multidimensional cross-sectional study. American Journal of Gastroenterology, 89, 1219-1225.

83. Levenstein, S., Prantera, C., Varvo, V., Scribano, M. L., Berto, E., Spinella, S. & Lanari, G. (1995). Patterns of biologic and psychologic risk factors for duodenal ulcer. Journal of Clinical Gastroenterology, 21, 110-117. 

84. Levy, M. (1974). Aspirin use in patients with major upper gastrointestinal bleeding and peptic ulcer disease. New England Journal of Medicine, 290, 1158-1162. 

85. Lewis, M. C. (1988). Attributions and inflammatory bowel disease: Patients' perceptions of illness causes and the effects of these perceptions on relationships. American Association of Registered Nurses Newsletter, 44, 16-17.

86. Livingston, E. H., Garrick, T. R., Scremin, O. U., Yasue, N., Passaro, E. P. & Guth, P. H. (1993). Heterogeneous distribution of gastric mucosal blood flow with restraint stress in the rat. Digestive Diseases and Sciences, 38, 1233-1242. 

87. Loof, L., Adami, H., Bates, S., Fagerstrom, K., Gustavsson, S., Nyberg, A., Nyren, O. & Brodin, U. (1987). Psychological group counseling for the prevention of ulcer relapse. Journal of Clinical Gastroenterology, 9, 400-407.

88. Maass, M., Bartels, C., Engel, P. M., Mamat, U. & Sievers, H. H. (1998). Endovascular presence of the viable Chlamydia pneumoniae is a common phenomenon in coronary artery disease. Journal of the American College of Cardiology, 31, 827-832. 

89. Malaty, H. M. & Graham, D. Y. (1994). Importance of childhood socioeconomic status on the current prevalence of Helicobacter pylori infection. Gut, 35, 742-745. 

90. Marucha, P. T., Kiecolt-Glaser, J. K. & Favagehi, M. (1998). Mucosal wound healing is impaired by examination stress. Psychosomatic Medicine, 60, 362-365.

91. Matsushima, Y., Aoyama, N., Fukuda, H., Kinoshita, Y., Todo, A., Himeno, S., Fujimoto, S., Kasuga, M., Nakase, H. & Chiba, T. (1999). Gastric ulcer formation after the Hanshin-Awaji earthquake: A case study of Helicobacter pylori infection and stress-induced gastric ulcers. Helicobacter, 4, 94-99. 

92. Maunder, R. (2000). Mediators of stress effects in inflammatory bowel disease: Not the usual suspects. Journal of Psychosomatic Research, 48, 569-577.

93. Maunder, R. & Esplen, M. J. (1999). Facilitating adjustment to inflammatory bowel disease: A model of psychosocial intervention in non-psychiatric patients. Psychotherapy and Psychosomatics, 68, 230-240.

94. Maunder, R., Lancee, W., Greenberg, G., Hunter, J. & Fernandes, B. (2000). Insecure attachment in a subgroup of ulcerative colitis defined by ANCA status. Digestive Diseases and Sciences, 45, 2127-2132.

95. Maunder, R. G., de Rooy, E. C., Toner, B. B., Greenberg, G. R., Steinhart, A. H., McLeod, R. S. & Cohen, Z. (1997). Health-related concerns of people who receive psychological support for inflammatory bowel disease. Canadian Journal of Gastroenterology, 11, 681-685.

96. Mayer, E. A. (2000). The neurobiology of stress and gastrointestinal disease. Gut, 47, 861-869.

97. McIntosh, J. H., Nasiry, R. W., McNeil, D., Coates, C., Mitchell, H. & Piper, D. W. (1985). Perception of life event stress in patients with chronic duodenal ulcer: A comparison of the rating of life events by duodenal ulcer patients and community controls. Scandinavian Journal of Gastroenterology, 20, 563-568. 

98. Medalie, J. H., Stange, K. C., Zyzanski, S. J. & Goldbourt, U. (1992). The importance of biopsychosocial factors in the development of duodenal ulcer in a cohort of middle-aged men. American Journal of Epidemiology, 136, 1280-1287.

99. Meddings, J. B. & Swain, M. G. (2000). Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat. Gastroenterology, 119, 1019-1028. 

100. Mee, A. S. & Jewell, D. P. (1978). Factors inducing relapse in inflammatory bowel disease. British Medical Journal, 2, 801-802. 

101. Mendeloff, A. J., Monk, M., Siegel, C. I. & Lilienfeld, A. (1970). Illness experience and life stresses in patients with irritable colon and with ulcerative colitis. New England Journal of Medicine, 282, 14-17.

102. Mirsky, A. (1958). Physiologic, psychologic, and social determinants in the etiology of duodenal ulcer. American Journal of Digestive Diseases, 3, 285-313.

103. Misiewicz, J. J., Lennard-Jones, J. E., Connell, A. M., Barton, J. H. & Jones, F. A. (1965). Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis. Lancet, 1, 185-188. 

 104. Mitchell, C. M. & Drossman, D. A. (1987). Survey of the AGA membership relating to patients with functional gastrointestinal disorders. Gastroenterology, 92, 1282-1284.

105. Mittelmann, B. & Wolff, H. G. (1942). Emotions and gastroduodenal function: Experimental studies on patients with gastritis, duodenitis, and peptic ulcer. Psychosomatic Medicine, 4, 5-61.

106. Mittermaier, C., Beier, M., Tillinger, W., Gangl, A. & Moser, G. (1998). Correlations between depressive mood and disease activity in patients with Inflammatory Bowel Disease (IBD)—a prospective study. Psychosomatic Medicine, 60, 96 [Abstract]. 

107. Miwa, H., Matsushima, H., Terai, T., Tanaka, H., Kawabe, M., Namihisa, A., Watanabe, S. & Sato, N. (1998). Relapsed duodenal ulcer after cure of Helicobacter pylori infection. Journal of Gastroenterology, 33, 556-561. 

108. Monjan, A. (1981). Stress and immunologic competence: Studies in animals. In R. Ader (Ed.), Psychoneuroimmunolog y (pp. 185–228). New York: Academic Press.

109. Monk, M., Mendeloff, A. I., Siegel, C. I. & Lilienfeld, A. (1970). An epidemiological study of ulcerative colitis and regional enteritis among adults in Baltimore: III. Psychological and possible stress-precipitating factors. Journal of Chronic Disease, 22, 564-578. 

110. Munck, A. & Guyre, P. M. (1991). Glucocorticoids and immune function. In R. Ader, D. L. Felten, & N. Cohen (Eds.), Psychoneuroimmunolog y (5th ed., pp. 447–474). San Diego, CA: Academic Press.

111. Nasiry, R. W., McIntosh, J. H., Byth, K. & Piper, D. W. (1987). Prognosis of chronic duodenal ulcer: A prospective study of the effects of demographic and environmental factors and ulcer healing. Gut, 28, 533-540. 

112. Natelson, B. J., Dubois, A. & Sodetz, F. J. (1977). Effect of multiple stress procedures on monkey gastroduodenal mucosa, serum gastrin and hydrogen ion kinetics. American Journal of Digestive Diseases, 22, 888-897.

113. (1994). Helicobacter pylori in peptic ulcer disease. Journal of the American Medical Association, 272, 65-69. 

114. Netterstrøm, B. & Kuel, K. (1990). Peptic ulcer among urban bus drivers in Denmark. Scandinavian Journal of Social Medicine, 18, 97-102.

115. Nice, D. S., Garland, C. F., Hilton, S. M., Baggett, J. C. & Mitchell, R. E. (1996). Long-term health outcomes and medical effects of torture among US Navy prisoners of war in Vietnam. Journal of the American Medical Association, 276, 375-381.

116. Nigro, G., Angelini, G., Grosso, S., Caula, G. & Sategna-Guidetti, C. (2001). Psychiatric predictors of noncompliance in inflammatory bowel disease: Psychiatry and compliance. Journal of Clinical Gastroenterology, 32, 66-68. 

117. North, C. S., Alpers, D. H., Helzer, J. E., Spitznagel, E. L. & Clouse, R. E. (1991). Do life events or depression exacerbate inflammatory bowel disease? A prospective study. Annals of Internal Medicine, 114, 381-386.

118. O'Sullivan, M., Breslin, N. P., Harman, I., Clayton, N., Bountra, C., McLaren, A. & O'Morain, C. A. (1999). Increased mucosal mast cells in irritable bowel syndrome (IBS). Gastroenterology, 114, 816 [Abstract]. 

119. Paar, G. H., Bezzenberger, U. & Lorenz-Meyer, H. (1988). Über den Zusammenhang von psychosozialem Streb und Krankheitsactivität bei Patienten mit Morbus Crohn und Colitis ulcerosa. Zeitschrift fur Gastroenterologie, 26, 648-657 [About the correlation of psychosocial stress and disease activity in patients with Crohn's disease and ulcerative colitis].

120. Padgett, D. A., Marucha, P. T. & Sheridan, J. F. (1998). Restraint stress slows cutaneous wound healing in mice. Brain, Behavior and Immunity, 12, 64-73.

121. Payne, A. & Blanchard, E. B. (1995). A controlled comparison of cognitive therapy and self-help support groups in the treatment of irritable bowel syndrome. Journal of Consulting and Clinical Psychology, 63, 779-786.

122. Peek, R. M. & Blaser, M. J. (1997). Pathophysiology of Helicobacter pylori-induced gastritis and peptic ulcer disease. American Journal of Medicine, 102, 200-207. 

123. Peters, M. N. & Richardson, C. T. (1983). Stressful life events, acid hypersecretion, and ulcer disease. Gastroenterology, 84, 114-119.

124. Peterson, W. L., Barnett, C. C., Evans, D. J., Feldman, M., Carmody, T., Richardson, C., Walsh, J. & Graham, D. Y. (1993). Acid secretion and serum gastrin in normal subjects and patients with duodenal ulcer: The role of Helicobacter pylori. American Journal of Gastroenterology, 88, 2038-2043. 

125. Piper, D. W., McIntosh, J. H., Ariotti, D. E., Calogiuri, J. V., Brown, R. W. & Shy, C. M. (1981). Life events and chronic duodenal ulcer: A case control study. Gut, 22, 1011-1017. 

126. Pomakov, P., Gueorgieva, S., Stantcheva, J., Tenev, T. & Rizov, A. (1993). Ulcères gastro-duodenaux pendant la periode d'une crise economique aigue. Journal de Radiologie, 74, 265-267 [Gastroduodenal ulcers during a period of acute economic crisis.]. 

127. Porcelli, P., Leoci, C., Guerra, V., Taylor, G. J. & Bagby, R. M. (1996). A longitudinal study of alexithymia and psychological distress in inflammatory bowel disease. Journal of Psychosomatic Research, 41, 569-573.

128. Prantera, C., Kohn, A., Mangiarotti, R., Andreoli, A. & Luzi, C. (1994). Antimycobacterial therapy in Crohn's disease: Results of a controlled, double-blind trial with a multiple antibiotic regimen. American Journal of Gastroenterology, 89, 513-518. 

129. Prugh, D. G. (1951). The influence of emotional factors on the clinical course of ulcerative colitis in children. Gastroenterology, 18, 339-354. 

130. Qiu, B. S., Vallance, B. A., Blennerhassett, P. A. & Collins, S. M. (1999). The role of CD4+ lymphocytes in the susceptibility of mice to stress-induced reactivation of experimental colitis. Nature Medicine, 5, 1178-1182.

131. Rampton, D. S., McNeil, N. I. & Sarner, M. (1983). Analgesic ingestion and other factors preceding relapse in ulcerative colitis. Gut, 24, 187-189. 

132. Rauws, E. A. J. & Tytgat, G. N. J. (1990). Cure of duodenal ulcer associated with eradication of Helicobacter pylori. Lancet, 335, 1233-1235.

133. Reynolds, J. C., Schoen, R. E., Maislin, G. & Zangari, G. G. (1994). Risk factors for delayed healing of duodenal ulcers treated with famotidine and ranitidine. American Journal of Gastroenterology, 89, 571-580. 

134. Riley, S. A., Mani, V., Goodman, M. J. & Lucas, S. (1990). Why do patients with ulcerative colitis relapse. Gut, 31, 179-183.

135. Robertson, D. A. F., Ray, J., Diamond, I. & Edwards, J. G. (1989). Personality profile and affective state of patients with inflammatory bowel disease. Gut, 30, 623-626.

136. Rogers, M., Trentham, D., McCune, W., Ginsberg, B., Kennke, H., Reich, P. & David, J. (1980). Effect of psychological stress on the induction of arthritis in rats. Arthritis Rheumatism, 23, 1337-1342. 

137. Rubinstein, A. & Davidovitch, Y. (1992). Half-mustache—A clue to peptic ulcer. Journal of Clinical Gastroenterology, 15, 96-98. 

138. Sartor, R. (1995). Current concepts of the etiology and pathogenesis of ulcerative colitis and Crohn's disease. Gastroenterology Clinics of North America, 24, 475-507.

139. Sartor, R. B. (1997). Enteric microflora in IBD: Pathogens or commensals. Inflammatory Bowel Disease, 3, 230-235. 

140. Sartor, R. B. (1997). Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases. American Journal of Gastroenterology, 92, 5S-11S (Suppl. 12). 

141. Saunders, P. R., Hanssen, N. P. & Perdue, M. H. (1997). Cholinergic nerves mediate stress-induced intestinal transport abnormalities in Wistar-Kyoto rats. The American Journal of Physiology, 273, G486-490 (2, Pt. 1). 

142. Saunders, P. R., Kosecka, U., McKay, D. M. & Perdue, M. H. (1994). Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine. The American Journal of Physiology, 267, G794-799 5, Pt. 1.

143. Schwarz, S. P. & Blanchard, E. B. (1990). Inflammatory bowel disease: A review of the psychological assessment and treatment literature. Annals of Behavioral Medicine, 12, 95-105.

144. Schwarz, S. P. & Blanchard, E. B. (1991). Evaluation of a psychological treatment for inflammatory bowel disease. Behaviour Research and Therapy, 29, 167-177.

145. Schwarz, S. P., Blanchard, E. B., Berreman, C. F., Scharff, L., Taylor, A. E., Greene, B. R., Suls, J. M. & Malamood, H. S. (1993). Psychological aspects of irritable bowel syndrome: Comparisons with inflammatory bowel disease and nonpatient controls. Behaviour Research and Therapy, 31, 297-304.

146. Segawa, K., Nakazawa, S., Tsukamoto, Y., Kurita, Y., Goto, H., Jukui, A. & Takano, K. (1987). Peptic ulcer is prevalent among shift workers. Digestive Diseases and Sciences, 32, 449-453.

147. Sessa, R., Di Pietro, M., Santino, I., del Piano, M., Varveri, A., Dagianti, A. & Penco, M. (1999). Chlamydia pneumoniae infection and atherosclerotic coronary disease. American Heart Journal, 137, 1116-1119. 

148. Sewitch, M., Dobkin, P., Abrahamowicz, M., Bitton, A., Daly, D., Wild, G., Cohen, A., Katz, S. & Szego, P. (2001). Psychological distress, social support and disease activity in inflammatory bowel disease. American Journal of Gastroenterology, 96, 1470-1479. 

149. Siegler, I., Levenstein, S., Feaganes, J. R. & Brummett, B. H. (2000). Personality before and after illness onset among patients with inflammatory bowel disease: A controlled, prospective study. Psychosomatic Medicine, 62, 151 [Abstract]. 

150. Soderholm, J. D. & Perdue, M. H. (2001). Stress and the gastrointestinal tract: II. Stress and intestinal barrier function. American Journal of Physiology: Gastrointestinal and Liver Physiology, 280, G7-G13. 

151. Sonnenberg, A. (1987). Changes in physician visits for gastric and duodenal ulcer in the United States during 1958–1984 as shown by National Disease and Therapeutic Index (NDTI) . Digestive Diseases and Sciences, 32, 1-7.

152. Sonnenberg, A. (1988). Factors which influence the incidence and course of peptic ulcer. Scandinavian Journal of Gastroenterology, 155, 119-140 (Suppl.). 

153. Sonnenberg, A., Mûller-Lissner, S. A., Vogel, E., Schid, P., Gonvers, A. J. J., Peters, P., Strohmener, G. & Blum, A. (1981). Predictors of duodenal ulcer healing and relapse. Gastroenterology, 81, 1061-1067. 

154. Sontag, S., Graham, D. Y., Belsito, A., Weiss, J., Farley, A. & Grant, R. (1984). Cimetidine, cigarette smoking, and recurrence of duodenal ulcer. The New England Journal of Medicine, 311, 689-693.

155. Spicer, C. C., Stewart, D. N. & Winser, D. M. R. (1944). Perforated peptic ulcer during the period of heavy air raids. Lancet, i, 14. 

156. Spiro, H. M. (1990). Six physicians with inflammatory bowel disease. Journal of Clinical Gastroenterology, 12, 636-642. 

157. Sriram, S., Stratton, C. W., Yao, S., Tharp, A., Ding, L., Bannan, J. D. & Mitchell, W. M. (1999). Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Annals of Neurology, 46, 6-14.

158. Steptoe, A., Wardle, J., Pollard, T. M., Canaan, L. & Davies, G. J. (1996). Stress, social support and health-related behavior: A study of smoking, alcohol consumption and physical exercise. Journal of Psychosomatic Research, 41, 171-180.

159. Sullivan, A. J. (1936). Psychogenic factors in ulcerative colitis. American Journal of Digestive Diseases and Nutrition, 2, 651-656. 

160. Svedlund, J. & Sjodin, I. (1985). A psychosomatic approach to treatment in the irritable bowel syndrome and peptic ulcer disease with aspects of the design of clinical trials. Scandinavian Journal of Gastroenterology, 109, 147-151 (Suppl.). 

161. Tysk, C., Lindberg, E., Jarnerot, G. & Floderus-Myrhed, B. (1988). Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut, 990-996. 

162. Van Heck, G. L., Vingerhoets, J. J. M. & Van Hout, G. C. M. (1991). Coping and extreme response tendency in duodenal ulcer patients. Psychosomatic Medicine, 53, 566-575.

163. Vandenbergh, V., Amery, W. K. & Waelkens, J. (1987). Trigger factors in migraine: A study conducted by the Belgian Migraine Society. Headache, 27, 191-196.

164. Vessey, M., Jewell, K., Smith, A., Yeates, D. & McPherson, K. (1986). Chronic inflammatory bowel disease, cigarette smoking, and use of oral contraceptives: Findings in a large cohort of women of childbearing age. British Medical Journal, 292, 1101-1103. 

165. Walan, A., Bianchi-Porro, G., Hentschel, E., Bardhan, K. D. & Delattre, M. (1987). Maintenance treatment with cimetidine in peptic ulcer disease for up to 4 years. Scandinavian Journal of Gastroenterology, 22, 397-405. 

166. Walker, E. A., Roy-Byrne, P. P., Katon, W. J., Li, L., Amos, D. & Jiranek, F. (1990). Psychiatric illness and irritable bowel syndrome: A comparison with inflammatory bowel disease. American Journal of Psychiatry, 147, 1656-1661.

167. Walker, P. M. & Feldman, M. (1992). Psychosomatic aspects of peptic ulcer disease: A multifactorial model of stress. Gastroenterology International, 5, 33-47. 

168. Weiner, H. (1991). From simplicity to complexity (1950–1990), the case of peptic ulceration—I: Human Studies. Psychosomatic Medicine, 53, 467-490.
Abstract | Cited by 2 

169. Whitehead, W. E. (1992). Behavioral medicine approaches to gastrointestinal disorders. Journal of Consulting and Clinical Psychology, 60, 605-612.

170. Whitehead, W. E., Crowell, M. D., Robinson, J. C., Heller, B. R. & Schuster, M. M. (1992). Effects of stressful life events on bowel symptoms: Subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. Gut, 33, 825-830.

171. von Wietersheim, J., Kohler, T. & Feiereis, H. (1992). Relapse-precipitatin g life events and feelings in patients with inflammatory bowel disease. Psychotherapy and Psychosomatics, 58, 103-112.

172. Wilhelmsen, I., Tangen, T., Ursin, H. & Berstad, A. (1994). Effect of short-term cognitive psychotherapy on recurrence of duodenal ulcer: A prospective randomized trial. Psychosomatic Medicine, 56, 440-448.

173. Wilson, L. M. & Baldwin, A. L. (1998). Effects of environmental stress on the architecture and permeability of the rat mesenteric microvasculature. Microcirculation, 5, 299-308.

174. Wolf, S. (1981). The psyche and the stomach: A historical vignette. Gastroenterology, 80, 605-614.

 175. Wyatt, J., Vogelsang, H., Hubl, W., Waldhoer, T. & Lochs, H. (1993). Intestinal permeability and the prediction of relapse in Crohn's disease. Lancet, 341, 1437-1439.