Psyche und entzündliche Darmkrankheiten: Von Alexander zur Swiss Inflammatory Bowel Disease Kohortenstudie

1. Psyche und entzündliche Darmkrankheiten: Von Alexander zur Swiss Inflammatory Bowel Disease Kohortenstudie Roland von Känel Jahrestagung der SAPPM Aarau 26. April, 2012 Kompetenzbereich für Psychosomatische Medizin der Universitätsklinik für Allgemeine Innere Medizin

2. Acknowledgments • SWISS IBD Cohort Study Group * • Stefan Begré • Rafael Cámara • Marie-Louise Gander • Pascal Juillerat • Paul Lukas • Valérie Pittet • Alain Schoepfer • Roger Ziegler • Swiss National Science Foundation • Our patients! * Principal Investigators: Pierre Michetti, Gerhard Rogler

3. Overview • Inflammatory Bowel Diseases (IBD) • Psychosocial Factors and IBD: The History of a Scientific Quest • Scientific Questions Asked in the Mental Health Core Project • Main Findings from the Mental Health Core Project • Conclusions • Clinical Approach

4. Ulcerativecolitis • Symptoms • Bloodydiarrhea • Abdominalcramps • Fever • Affectedsites • Onlytoplayers of thecolon or rectum (95%) • Inflammationmoves up thecolon Crohn‘s disease • Symptoms • Diarrhea • Rectal bleeding • Abdominal pain • Weight loss • Extraintestinal manifestations • Affected sites • Deep in the lining of the wall of the entire GIT (rectum 50%) • Skip lesions

5. Overview • Inflammatory Bowel Diseases (IBD) • Psychosocial Factors and IBD: The History of a Scientific Quest • Scientific Questions Asked in the Mental Health Core Project • Main Findings from the Mental Health Core Project • Conclusions • Clinical Approach

6. Psychosocial Factors are Widely Believed to Play a Role in IBD • 45% of patients think stress triggers IBD attacks. • Gastroenterologists consider psychosocial factors to be important in the course of IBD. • A state-of-the-art monograph said in 1990: „Stress...has been positively correlated with exacerbation of disease“. American Psychosomatic Society Online Educational Resources

7. Alexander‘s „Holy Seven“ psychosomatic diseases • Essential Hypertension • Asthma • Neurodermaitis • Peptic ulcer • Hyperthyreoidism • Rheumatoid arthritis • Ulcerative colitis Alexander, Psychosomatic Medicine. Norton: New York, 1950 „The physiological, the psychological, and the sociological approaches begin to be integrated into a comprehensive understanding of man. Future advancements of psychotherapy will evolve from such an approach.“ Alexander, Psychosom Med 1962;24:13

8. The Psychoanalysis of Ulcerative Colitis • A psychoanalytic formula for five patients undergoing analysis because of ulcerative colitis: • The most common onset situation in colitis cases is one in which the patient has lost hope and is convinced that he cannot accomplish the task at hand. He then regresses to an infantile form of accomplishment, which is gastrointestinal elimination. Alexander, Eisenstein, Grotjahn. Psychoanalytic pioneers. Basic Books: New York, 1966, pp. 392-393.

9. The Psychology of Ulcerative Colitis and Crohn‘s Disease • Over time, the working psychoanalytic premise regarding U.C. symptomatology is the following: „Individuals with characterological difficulty in expressing rage, when threatened by separation from an important object, implode the rage inward and thereby inflame and damage their intestinal lining.“ • „A syndrome medically very similar to ulcerative colitis, Crohn’s disease...“ Gerson, Psychoanal Psychol 2002;19:380

10. Psychosocial Aspects and IBD: Views of a Century • First half of the 20thcentury: Crohn‘sdisease and ulcerativecolitisamongsttheclassicalpsychosomaticdisorders. • 1950s: Heyday of (psychoanalytic) psychosomaticmedicine: Franz Alexander named IBD one of the “holy seven” psychosomatic disorders assigning specific personal conflicts to the onset of IBD. • 1960s: Autoimmunhypothesis of IBD & Introduction of steriods: Aronowitz & Spiro: Therise and fall of thepsychosomatichypothesis in ulcerativecolitis. J ClinGastroenterol 1988. • Today‘sbio-psycho-socialview: Psychosocialfactorscontribute to thediseasecoursebutprobably not to theonset of IBD. • Psychoneuroendocrinology and -immunology: E.g. Stress increasescolonpermeability and affectsmurineimmunologicalprocesses. Hollander, J Physiol Pharmacol 2003

11. Systematic Review Digestion 2009; 80:129-139

12. Main Results from the Literature Review • 13 out of 18 studies reported significant relationships betweens stress and adverse outcomes (CDAI, endoscopic signs, symptom diaries): CD>UC>mixed IBD samples. • Perceived stress, depression, life events, daily hassles. • Sample sizes between 10 and 155 participants. • Substantial variability between studies in terms of patient assessment, control variables (e.g. medications mentioned in only 8 studies), and psychometric instruments.  Larger sample sizes (power) and sound adjustments for covariates are required!

13. Overview • Inflammatory Bowel Diseases (IBD) • Psychosocial Factors and IBD: The History of a Scientific Quest • Scientific Questions Asked in the Mental Health Core Project • Main Findings from the Mental Health Core Project • Conclusions • Clinical Approach

14. Core Project „Mental Health“ – StudyHypothesesThus far Investigated: • Psychosocialfactorspredictdiseaserelapse(hardoutcome) • Psychosocialfactorsmediate or moderatetheeffect of established risk factors of IBD on thediseasecourse • Psychosocialfactorsare associated with inflammatoryactivity (intermediateoutcomes)

15. Main Question Answered: Do Psychosocial Factors Predict the Course of Crohn‘s Disease? YES! • Validated self-rated questionnaires asking into different domains of psychosocial stress, distress, and quality of life. • Between 313 and 468 patients with CD • Follow-up time: between 12 and 18 months • Outcomes: Flares, non-response to therapy, complications, extraintestinal manifestations; alone or combined • Preselected control variables: age, sex, education, family history, disease duration, previous hospitalizations, baseline disease activity, life style, BMI, medications

16. Overview • Inflammatory Bowel Diseases (IBD) • Psychosocial Factors and IBD: The History of a Scientific Quest • Scientific Questions Asked in the Mental Health Core Project • Main Findings from the Mental Health Core Project • Conclusions • Clinical Approach

17. Intern Med J 2012 (in press) • 316 CD patients completed IBDQ and SF-36 at study enrolment; observed flares during 12 months • Flares: increase of ≥100 points in CDAI („clinically active“) • 2-fold (99%CI: 1.1-4.0) decrease in the odds of flares per 1 SD increase of gastrointestinal QoL • 3-fold (99%CI: 1.5-6.2) decrease in the odds of flares per 1 SD increase of general mental & physical QoL

18. Inflamm Bowel Dis 2011 • 486 patients with CD completed the perceived stress scale and the Hospital Anxiety and Depression Scale • PSS: 30 items (score 30-120) covering the last 2 yrs; e.g., „you have too many things to do“ • Follow-up: 18 months • CD exacerbation: flares, need for more aggressive medication, occurrence of extraintestinal manifestations, and complications.

19. Results • Perceived stress score: 61±17 HADS Depression score: 4.3±3.9 HADS Anxiety score: 6.7±4.3 • 1 SD of perceived stress increased the odds of disease exacerbation by 1.85 (95% CI: 1.43-2.40) • After removal of the anxiety and the depression components, an association of perceived stress with disease exacerbation was no longer detectable. • The role of perceived stress for exacerbation of CD is fully attributable to its mood components (anxiety & depression).

20. 468 patients with CD, follow-up 18 months • Outcome = disease exacerbation: flares, extraintestinal manifestations, complications and non-response to therapy • Posttraumatic diagnostic scale: score 0-51 points; patients with a score ≥15 are likely to have fully developed PTSD Frontline Gastroenterol 2011

21. PDS score 8.8±8.0, 19% of patients had a PDS score ≥15 OR for exacerbation for 1 SD increase in the PDS score:

22. Patients with a PDS score ≥15:- 4.3-fold higher risk for disease exacerbation than patients with a PDS score <15- 13-fold higher risk for disease exacerbation than patients with a PDS score = 0

23. E-mail of a Mother of a Daughter with CD (December 8, 2010) Dear Professor von Kanel, I have searched quite a while for studies focusing on the impact of chronic disease, especially Crohn's upon the emotional state of a patient and so was quite excited to have found „Post-traumatic stress in Crohn's disease and its association with disease activity“. ...my 27-year-old daughter who suffered Crohn‘s disease more than 10 years, was revived after extreme trauma last year and is now attempting to reconfigure her life post surgery. ...it is clear that Europe is light years ahead of the US in novel and successful treatments for Crohn's.Thank you for studying this important aspect of illness. Best regards, C. E.

24. 458 patients with CD, follow-up 18 months • Outcome: disease deterioration as combined flares, extraintestinal manifestations, complications and non-response to therapy • ENRICHD Social Support Inventory: score 6-30 points; 6 items covering emotional, practical, and informational support Inflamm Bowel Dis 2011

25. ENRICHD Social Support Inventory

26. Higher level of social support is associated with a more favorable disease course! • Mean social support score: 24.3±5.5 • The odds of disease deterioration decreased by 1.50-times (95% CI: 1.16-1.94) for an increase of 1 SD of soc. supp. • A 1-SD decrease of BMI from the mean (i.e., BMI of 19 kg/m2) increased the risk of disease deteoriation by 1.43 (95% CI: 1.04-1.96). • Moderator effect: In case of low BMI (i.e., 1 SD below the mean of 19 kg/m2), the risk decreased by 1.80-times (95% CI 1.32-2.46) for an increase of 1 SD of soc. supp. - Adverse effect of low BMI was buffered with high support.

27. Overview • Inflammatory Bowel Diseases (IBD) • Psychosocial Factors and IBD: The History of a Scientific Quest • Scientific Questions Asked in the Mental Health Core Project • Main Findings from the Mental Health Core Project • Conclusions • Clinical Approach

28. What have we learned? • Good evidence for psychosocial factors predicting the course of CD independent of other prognostic factors. • Depression, anxiety, and posttraumatic stress are „bad for the gut“, whereas good QoL and high social support are „good for the gut“. • Whether some psychosocial factors are more important than others is unclear (depression?) • Therapeutic interventions targeting psychosocial factors could be inferred to benefit distress levels and possibly adverse outcomes...CBT, trauma therapy, enhancing QoL and social support.

29. However: Cochrane Database Systematic Review • There is evidence for efficacy of psychological therapy (education, complex stress management programs) in adolescent patients with IBD, but not in adult IBD patients. • Adults: psychotherapy had no effect on QoL at around 12 months, depression, or proportion of patients not in remission. Results were similar at 3 to 8 months. • There was no evidence for statistical heterogeneity or subgroup effects (type of disease or therapy intensity). • Adolescents: positive short term effects of psychotherapy on most outcomes, including QoL and depression. Timmer et al., Psychological interventions for treatment of inflammatory bowel disease. Cochrane Database Syst Rev 2011

30. Overview • Inflammatory Bowel Diseases (IBD) • Psychosocial Factors and IBD: The History of a Scientific Quest • Scientific Questions Asked in the Mental Health Core Project • Main Findings from the Mental Health Core Project • Conclusions • Clinical Approach

31. Implications for Clinical Practice • Adolescents with IBD may benefit from psychological treatment. • General application of psychological therapy in adult patients with IBD is not recommended. • In adults, the need of psychological interventions should be assessed and psychotherapy, stress management programmes or educational training offered on an individual basis. Timmer et al., Cochrane Database Syst Rev 2011

32. German Guidelines for Psychosomatic Treatment of UC • High disease activity may be associated with increased levels of psychological symptoms (depression, anxiety etc.) and impairs QoL. • Patients with sustained GI pain or diarrhoe which cannot be explained by diseases activity or complications should be investigated for irritable bowel syndrome and depression. • IBS and depression should be treated according to current guidelines, including psychotherapy and antidepressants. • Psychosocial aspects and disease-related QoL should be part of medical consultations and considered for therapy. Psychiatrist/ psychosomatic specialist should be part of the treatment network. • Education about the disease and guided self-control are crucial elements of patient care. • Complementary and alternative medicine only in accordance with evidence-based guidelines. Clinicians should inform themselves. Dignas et al., Z Gastroenterol 2011;49:1276

33. Thank you for your attention!