Psyche und entz

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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
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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
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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

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• Crohns 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

• Ulcerative colitis
• Symptoms
• Bloody diarrhea
• Abdominal cramps
• Fever
• Affected sites
• Only top layers of the colon or rectum (95)
• Inflammation moves up the colon

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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

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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
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Alexanders 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 19622413
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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.
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The Psychology of Ulcerative Colitis and Crohns
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, Crohns disease...

Gerson, Psychoanal Psychol 200219380
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Psychosocial Aspects and IBD Views of a Century

• First half of the 20th century Crohns disease
  and ulcerative colitis amongst the classical
  psychosomatic disorders.
• 1950s Heyday of (psychoanalytic) psychosomatic
  medicine 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 The rise and fall
  of the psychosomatic hypothesis in ulcerative
  colitis. J Clin Gastroenterol 1988.
• Todays bio-psycho-social view Psychosocial
  factors contribute to the disease course but
  probably not to the onset of IBD.
• Psychoneuroendocrinology and -immunology E.g.
  Stress increases colon permeability and affects
  murine immunological processes.

Hollander, J Physiol Pharmacol 2003
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Systematic Review
Digestion 2009 80129-139
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Main Results from the Literature Review

• 13 out of 18 studies reported significant
  relationships betweens stress and adverse
  outcomes (CDAI, endoscopic signs, symptom
  diaries) CDgtUCgtmixed 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!
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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

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Core Project Mental Health Study Hypotheses
Thus far Investigated

• Psychosocial factors predict disease relapse
  (hard outcome)
• Psychosocial factors mediate or moderate the
  effect of established risk factors of IBD on the
  disease course
• Psychosocial factors are associated with
  inflammatory activity (intermediate outcomes)

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Main Question Answered Do Psychosocial Factors
Predict the Course of Crohns 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

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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

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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 (99CI 1.1-4.0) decrease in the odds of
  flares per 1 SD increase of gastrointestinal
  QoL
• 3-fold (99CI 1.5-6.2) decrease in the odds of
  flares per 1 SD increase of general mental
  physical QoL

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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.

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Results

• Perceived stress score 6117
  HADS
  Depression score 4.33.9
  HADS Anxiety
  score 6.74.3
• 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).

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• 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
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PDS score 8.88.0, 19 of patients had a PDS
score 15
OR for exacerbation for 1 SD increase in the
PDS score
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Patients with a PDS score 15- 4.3-fold higher
risk for disease exacerbation than patients with
a PDS score lt15 - 13-fold higher risk for
disease exacerbation than patients with a PDS
score 0
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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 Crohns 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.
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• 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
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ENRICHD Social Support Inventory
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Higher level of social support is associated with
a more favorable disease course!

• Mean social support score 24.35.5
• 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.

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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

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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.

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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
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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

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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
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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 2011491276
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Thank you for your attention!