title: Gray matter regions statistically mediating the cross-sectional association of eotaxin and set-shifting among older adults with major depressive disorder.
abstract: Eotaxin is a chemokine that exerts negative effects on neurogenesis. We recently showed that peripheral eotaxin levels correlate with both lower gray matter volume and poorer executive performance in older adults with major depressive disorder. These findings suggest that the relationship between eotaxin and set-shifting may be accounted for by lower gray matter volume in specific regions. Prior studies have identified specific gray matter regions that correlate with set-shifting performance, but have not examined whether these specific gray matter regions mediate the cross-sectional association between eotaxin and set-shifting.
  
  
  
  In 27 older adults (mean age: 68 ± 5.2 years) with major depressive disorder, we performed a whole brain (voxel-wise) analysis testing whether/where gray matter density statistically mediates the cross-sectional association of eotaxin and set-shifting performance.
  
  
  
  We found the association between eotaxin and set-shifting performance was fully statistically mediated by lower gray matter density in left middle cingulate, right pre-/post-central, lingual, inferior/superior frontal, cuneus, and middle temporal regions.
  
  
  
  The regions identified above may be both susceptible to a potential neurodegenerative effect of eotaxin, and critical to preserving set-shifting function. Longitudinal and intervention studies are needed to further evaluate whether targeting eotaxin levels will prevent neurodegeneration and executive impairment in older adults with depression. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Smagula
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Helmet T
authors.initials: HT
authors.lastname: Karim
authors.affiliation: Healthy Mind Lab, Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lenze
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Meryl A
authors.initials: MA
authors.lastname: Butters
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Wu
authors.affiliation: Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.|Department of Behavioral and Community Health Sciences, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reynolds
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.|Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Aizenstein
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D054413:Chemokine CCL11 / Q000097:blood*; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000097:blood* / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D054413:Chemokine CCL11
keywords: depression; eotaxin; executive function; geriatric; gray matter; immunology; magnetic resonance imaging (MRI); set-shifting