Gastroenterology
Volume 139, Issue 1 , Pages 48-57.e2, July 2010

Regional Gray Matter Density Changes in Brains of Patients With Irritable Bowel Syndrome

  • David A. Seminowicz

      Affiliations

    • Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada
    • Corresponding Author InformationReprint requests Address requests for reprints to: David A. Seminowicz, PhD, Alan Edwards Centre for Research on Pain, McGill University, Room M/19 Strathcona Anatomy & Dentistry, 3640 University Street, Montreal, Quebec H3A 2B2. fax: (514) 398-7464
  • ,
  • Jennifer S. Labus

      Affiliations

    • Center for Neurobiology of Stress, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California and VA Greater Los Angeles Health Care System
  • ,
  • Joshua A. Bueller

      Affiliations

    • Center for Neurobiology of Stress, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California and VA Greater Los Angeles Health Care System
  • ,
  • Kirsten Tillisch

      Affiliations

    • Center for Neurobiology of Stress, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California and VA Greater Los Angeles Health Care System
  • ,
  • Bruce D. Naliboff

      Affiliations

    • Center for Neurobiology of Stress, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California and VA Greater Los Angeles Health Care System
  • ,
  • M. Catherine Bushnell

      Affiliations

    • Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada
  • ,
  • Emeran A. Mayer

      Affiliations

    • Center for Neurobiology of Stress, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California and VA Greater Los Angeles Health Care System

Received 24 November 2009; accepted 22 March 2010. published online 29 March 2010.

Background & Aims

Several studies have examined structural brain changes associated with chronic pain syndromes, including irritable bowel syndrome (IBS), but study sample sizes have been small and heterogeneous.

Methods

We used magnetic resonance imaging–based techniques, voxel-based morphometry, and cortical thickness analysis to examine brain anatomical differences in a relatively large, tightly screened sample of IBS patients (n = 55); we compared data with that from healthy persons (controls; n = 48).

Results

IBS was associated with decreased gray matter density (GMD) in widespread areas of the brain, including medial prefrontal and ventrolateral prefrontal cortex, posterior parietal cortex, ventral striatum, and thalamus. Compared with controls, we observed increased GMD in patients with IBS in the pregenual anterior cingulate cortex and the orbitofrontal cortex, as well as trends in the posterior insula/secondary somatosensory cortex, (para)hippocampus, and left dorsolateral prefrontal cortex. In accounting for anxiety and depression, we found that several of the regions involved in affective processing no longer differed between patients with IBS and controls, whereas the differences in prefrontal and posterior parietal cortices remained. The areas of decreased GMD associated with IBS were largely consistent across clinical subgroups, based on predominant bowel habit and pain predominance of symptoms. No overall or regional differences were observed in cortical thickness between patients with IBS and controls.

Conclusions

Changes in density of gray matter among regions involved in cognitive/evaluative functions are specifically observed in patients with IBS, whereas changes in other areas of the brain can be explained by levels of anxiety and depression.

Keywords: Neuroimaging, Voxel-Based Morphometry, VBM, Neural

Abbreviations used in this paper: ACC, anterior cingulate cortex, aMCC, anterior midcingulate cortex, BA, Brodmann area, CSF, cerebrospinal fluid, CT, cortical thickness, CTA, cortical thickness analysis, DSM-IV, Diagnostic and Statistical Manual of Mental Disorders 4th edition, GLM, general linear model, GM, gray matter, GMD, gray matter density, IBS, irritable bowel syndrome, INS, insula, MFG, middle frontal gyrus, MRI, magnetic resonance imaging, OFC, orbitofrontal cortex, PAG, periaqueductal gray, PFC, prefrontal cortex, S2, secondary somatosensory cortex, UCLA, University of California Los Angeles, VBM, voxel-based morphometry

 

 Conflicts of interest E.A.M. has received research support from Avera Pharmaceuticals and GlaxoSmithKline. The remaining authors disclose no conflicts.

 Funding This work was supported by National Institutes of Health grants DK 64530 (E.A.M.), AT 00268 (E.A.M.), and DK 48351 (E.A.M.), DK 073451-01 (K.T.), DK 071626-04 (J.S.L.), DK 084169-01 (J.S.L.). D.A.S. was supported by a fellowship from the Canadian Institute of Health Research.

PII: S0016-5085(10)00482-8

doi:10.1053/j.gastro.2010.03.049

Gastroenterology
Volume 139, Issue 1 , Pages 48-57.e2, July 2010