title: Altered Markers of Brain Development in Crohn's Disease with Extraintestinal Manifestations - A Pilot Study.
abstract: OBJECTIVE
  Alterations of brain morphology in Crohn's disease have been reported, but data is scarce and heterogenous and the possible impact of disease predisposition on brain development is unknown. Assuming a systemic course of the disease, brain involvement seems more probable in presence of extraintestinal manifestations, but this question has not yet been addressed. The present study examined the relationship between Crohn's disease and brain structure and focused on the connection with extraintestinal manifestations and markers of brain development.
  
  
  METHODS
  In a pilot study, brains of 15 patients with Crohn's disease (of which 9 had a history of extraintestinal manifestations, i.e. arthritis, erythema nodosum and primary sclerosing cholangitis) were compared to matched healthy controls using high resolution magnetic resonance imaging. Patients and controls were tested for depression, fatigue and global cognitive function. Cortical thickness, surface area and folding were determined via cortical surface modeling.
  
  
  RESULTS
  The overall group comparison (i.e. all patients vs. controls) yielded no significant results. In the patient subgroup with extraintestinal manifestations, changes in cortical area and folding, but not thickness, were identified: Patients showed elevated cortical surface area in the left middle frontal lobe (p<0.05) and hypergyrification in the left lingual gyrus (p<0.001) compared to healthy controls. Hypogyrification of the right insular cortex (p<0.05) and hypergyrification of the right anterior cingulate cortex (p<0.001) were detected in the subgroup comparison of patients with against without extraintestinal manifestations. P-values are corrected for multiple comparisons.
  
  
  CONCLUSIONS
  Our findings lend further support to the hypothesis that Crohn's disease is associated with aberrant brain structure and preliminary support for the hypothesis that these changes are associated with a systemic course of the disease as indicated by extraintestinal manifestations. Changes in cortical surface area and folding suggest a possible involvement of Crohn's disease or its predisposition during brain development.
authors.affiliation: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Anne K
authors.identifier: http://orcid.org/0000-0002-7964-4284
authors.initials: AK
authors.lastname: Thomann
authors.affiliation: Department of Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Thomann
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Saarland University, Homburg, Germany.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Wolf
authors.affiliation: Department of Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.|Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Dusan
authors.initials: D
authors.lastname: Hirjak
authors.affiliation: Department of Psychosomatic Medicine, Central Institute for Mental Health Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schmahl
authors.affiliation: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Ebert
authors.affiliation: Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Szabo
authors.affiliation: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reindl
authors.affiliation: Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Griebe