Gray matter regions statistically mediating the cross-sectional association of eotaxin and set-shifting among older adults with major depressive disorder

Abstract

Objective: 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.

Method: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00892047.

Keywords: depression; eotaxin; executive function; geriatric; gray matter; immunology; magnetic resonance imaging (MRI); set-shifting.

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Copyright © 2016 John Wiley & Sons, Ltd.

Figures

Figure 1

Illustation of the model and paths examined

Figure 2

Regions where gray matter density statistically mediated the association between eotaxin and set-shifting. Colors show the effect size of the indirect effect parameter estimate (path A times path B), which are all negative. Top row, left to right: left middle cingulate, right cuneus, right postcentral/precentral gyrus, and right middle temporal gyrus. Bottom row, left to right: right lingual gyrus, right inferior frontal gyrus/insula, and right superior frontal gyrus.