Neurobiology of aging
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Neurobiology of aging · Jan 2013
Physical health and incident late-life depression: modification by cytokine genes.
Inflammatory cytokines have been implicated in the pathophysiology of depression, potentially underlying its association with worse physical health. Cytokine production is influenced by the transcriptional activity of several polymorphisms. We hypothesized that alleles related to higher proinflammatory and/or lower anti-inflammatory cytokine production would strengthen the association between physical disorders and late-life depression. ⋯ The associations between physical disorders and incident depression were significant in the presence of 2 alleles related to higher proinflammatory cytokine production (tumor necrosis factor-α -850T and IL-8 -251A), and 1 allele related to lower anti-inflammatory cytokine production (IL-4 +33C). Significant gene-environment interactions, independent of all covariates, were found for total number of risk alleles on both pro- and anti-inflammatory cytokine genes in addition to the above 3 individual single nucleotide polymorphisms. The present findings support cytokine-mediated inflammatory pathways underlying at least some of the well-recognized association between worse physical health and late-life depression, and provide novel evidence of a genetic basis for this.