ASSOCIATIONS BETWEEN CYTOKINES AND CORTICAL THICKNESS IN PATIENTS WITH LATE-LIFE DEPRESSION

Introduction Late-life depression (LLD), defined as depression that occurs after the age of 60 years, is associated with a poor quality of life, cognitive impairment, and increased morbidity and mortality. Immune factors are now recognized as involved in the pathophysiology of depression. We aimed to evaluate the relationship between plasma cytokine levels and cortical thickness in patients with LLD. Methods Blood samples and structural magnetic resonance imaging scans (Siemens 3T Prisma) were acquired in 29 older adults (≥60 years old) with major depression (62% female; mean age, 70.7 (7.3) years; mean MADRS 15.9 (3.2)). Associations between plasma cytokine levels (log-transformed) and cortical thickness were evaluated in a multivariate analysis using partial least squares. Cytokines with detectable levels in at least 27 of the 29 subjects (exotaxin, IFN-a2, GRO, MDC, IL-12(p70), sCD40L, IL-8, IP-10, MCP-1, MIP-1b, TNF-a, and VEGF) were included in the analysis. Results The first latent variable was significant (accounting for 32% of the cross-block covariance, p=.036) and reflected negative correlations between exotaxin, IL-8, IP-10, MIP-1b, and TNF-a levels and cortical thickness in numerous brain regions, including cingulate, insular, temporal, orbitofrontal, and prefrontal cortices (Figure 1). Conclusions Patients with LLD who have high plasma levels of exotoxin, IL-8, IP-10, MIP-1b, and TNF-a have less cortical thickness in brain regions previously implicated in depression than patients with LLD who have lower levels of these chemokines and pro-inflammatory cytokines. The affected brain regions have functions in self-referential processes, emotional regulation, social cognition, and attentional switching. Thus, the observed reductions in cortical thickness may contribute to the emotional, cognitive, and behavioral disturbances in LLD. Recently, chemokines have been implicated in many neurobiological processes and are considered to play a role in linking peripheral and central inflammation. The present results further support the importance of chemokines and proinflammatory cytokines in depressive pathophysiology. This research was funded by Sponsored by NIMH R01 MH097892, NCCIH AT009198, MH086481; Alzheimer's Research & Prevention Foundation, Allergan, PCORI; Advisory Board: Alzheimer's Research & Prevention Foundation; Royalties for books from Oxford University Press and Hopkins University Press.