title: Gene expression profiles in peripheral blood mononuclear cells correlate with salience network activity in chronic visceral pain: A pilot study.
abstract: BACKGROUND
  Distinct gene expression profiles in peripheral blood mononuclear cells (PBMCs) consistent with increased sympathetic nervous system activity have been described in different populations under chronic stress. Neuroinflammatory brain changes, possibly related to the migration of primed monocytes to the brain, have been implicated in the pathophysiology of chronic pain. Irritable bowel syndrome (IBS) is a stress-sensitive gastrointestinal disorder associated with altered brain-gut interactions and increased sympathetic/vagal tone and anxiety. Reports about immune alterations in IBS are conflicting. This pilot study aimed to test how PBMC gene expression inflammatory profiles are correlated with altered brain signatures in the salience system.
  
  
  METHODS
  Sixteen IBS and 16 healthy controls (HCs) completed resting state MRI scans. Gene expression profiles in PBMCs were assessed using human transcriptome array-2. Bioinformatic analyses determined differential expression of PBMCs between IBS and HCs. Partial least squares, a multivariate analysis technique, was used to identify disease correlations between PBMC gene expression profiles and functional activity in the brain's salience network.
  
  
  RESULTS
  Regions of the salience network, including the mid cingulate cortex, and mid and superior temporal gyrus were positively correlated with several pro-inflammatory genes (interleukin 6, APOL2) in IBS, but negatively correlated with several anti-inflammatory genes (KRT8, APOA4) in HCs.
  
  
  CONCLUSIONS
  Based on rodent studies, one may speculate that chronically activated stress signaling pathways in IBS maintain a pro-inflammatory state in the periphery. Alternatively, primed monocytes may migrate to the brain during stress, inducing regional neuroinflammatory changes in salience regions involved in the modulation of visceral sensitivity.
authors.affiliation: Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.|David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Vatche and Tamar Manoukin Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.affiliation: David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Department of Hematology-Oncology, UCLA, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cole
authors.affiliation: Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.|David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Vatche and Tamar Manoukin Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Labus
authors.affiliation: Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.|David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Vatche and Tamar Manoukin Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.|Center for Systems Biomedicine, UCLA, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Nguyen
authors.affiliation: Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.|David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Vatche and Tamar Manoukin Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Kilpatrick
authors.affiliation: Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.|David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Vatche and Tamar Manoukin Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.|Integrative Medicine, GLA, VHA, Los Angeles, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Tillisch
authors.affiliation: Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.|David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Vatche and Tamar Manoukin Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Naliboff
authors.affiliation: Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.|David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Vatche and Tamar Manoukin Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Chang
authors.affiliation: Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.|David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Vatche and Tamar Manoukin Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.|Ahmanson-Lovelace Brain Mapping Center, UCLA, Los Angeles, CA, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Mayer
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D059350:Chronic Pain / Q000235:genetics / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000235:genetics* / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D010865:Pilot Projects; D059467:Transcriptome; D059265:Visceral Pain / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D018836:Inflammation Mediators
keywords: anti-inflammatory genes; chronic visceral pain syndrome; immune system; peripheral blood mononuclear cells; pro-inflammatory genes; resting state brain activity; salience network