title: Mind-body interactions in the regulation of airway inflammation in asthma: A PET study of acute and chronic stress.
abstract: BACKGROUND
  Psychological stress has long been recognized as a contributing factor to asthma symptom expression and disease progression. Yet, the neural mechanisms that underlie this relationship have been largely unexplored in research addressing the pathophysiology and management of asthma. Studies that have examined the mechanisms of this relationship in the periphery suggest that it is the superimposition of acute stress on top of chronic stress that is of greatest concern for airway inflammation.
  
  
  METHODS
  We compared asthmatic individuals with high and low levels of chronic life stress in their neural and peripheral physiological responses to the Trier Social Stress Test and a matched control task. We used FDG-PET to measure neural activity during performance of the two tasks. We used both circulating and airway-specific markers of asthma-related inflammation to assess the impact of acute stress in these two groups.
  
  
  RESULTS
  Asthmatics under chronic stress had a larger HPA-axis response to an acute stressor, which failed to show the suppressive effects on inflammatory markers observed in those with low chronic stress. Moreover, our PET data suggest that greater activity in the anterior insula during acute stress may reflect regulation of the effect of stress on inflammation. In contrast, greater activity in the mid-insula and perigenual anterior cingulate seems to reflect greater reactivity and was associated with greater airway inflammation, a more robust alpha amylase response, and a greater stress-induced increase in proinflammatory cytokine mRNA expression in airway cells.
  
  
  CONCLUSIONS
  Acute stress is associated with increases in markers of airway inflammation in asthmatics under chronic stress. This relationship may be mediated by interactions between the insula and anterior cingulate cortex, that determine the salience of environmental cues, as well as descending regulatory influence of inflammatory pathways in the periphery.
authors.affiliation: Waisman Laboratory for Brain Imaging & Behavior and Center for Healthy Minds, University of Wisconsin-Madison, 1500 Highland Ave, Madison, WI 53705, USA. Electronic address: marosenk@wisc.edu.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Rosenkranz
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: Stephane
authors.initials: S
authors.lastname: Esnault
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Crisafi
authors.affiliation: Waisman Laboratory for Brain Imaging & Behavior and Center for Healthy Minds, University of Wisconsin-Madison, 1500 Highland Ave, Madison, WI 53705, USA.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Gresham
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Higgins
authors.affiliation: Department of Psychology, University of Wisconsin-Madison, 1202 W. Johnson St., Madison, WI 53706, USA.
authors.forename: Mollie N
authors.initials: MN
authors.lastname: Moore
authors.affiliation: Department of Counseling Psychology, University of Wisconsin-Madison, 1000 Bascom Mall, Madison, WI 53706, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Moore
authors.affiliation: Waisman Laboratory for Brain Imaging & Behavior and Center for Healthy Minds, University of Wisconsin-Madison, 1500 Highland Ave, Madison, WI 53705, USA; Osher Center for Integrative Medicine, University of California, San Francisco, 1701 Divisadero St #150, San Francisco, CA 94115, USA.
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Weng
authors.affiliation: Department of Psychology, University of Wisconsin-Madison, 1202 W. Johnson St., Madison, WI 53706, USA.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Salk
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.affiliation: Waisman Laboratory for Brain Imaging & Behavior and Center for Healthy Minds, University of Wisconsin-Madison, 1500 Highland Ave, Madison, WI 53705, USA; Department of Psychology, University of Wisconsin-Madison, 1202 W. Johnson St., Madison, WI 53706, USA; Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Blvd, Madison, WI 53719, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000681:Amylases / Q000378:metabolism; D001249:Asthma / Q000150:complications / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D008297:Male; D011014:Pneumonia / Q000150:complications; D049268:Positron-Emission Tomography; D012129:Respiratory Function Tests; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000681:Amylases; D006854:Hydrocortisone
keywords: ACC; Asthma; Cortisol; IL-1; IL-17; Inflammation; Insula; PET; Stress; TSST