Abstract
AimsClose to one third of patients with major depression show increases in pro-inflammatory cytokines, which are in turn associated with risk for inflammatory disease. Genetic variants that enhance immune reactivity may thus enhance inflammatory and depressive reactions to stress. The aim of the present study was to investigate a trio of functional SNPs in the promoter regions of IL6 (-174G>C, rs1800795), IL1β (-511C>T, rs16944), and TNF (-308G>A, rs1800629) as moderators of the relationship between chronic stress exposure and elevations in depressive symptoms.MethodsParticipants were 444 Australian youth (mean age = 20.12) whose exposure to chronic stress in the past 6 months was assessed using the semi-structured UCLA Life Stress Interview, and who completed the Beck Depression Inventory II at ages 15 and 20. Between ages 22 and 25, all participants in the selected sample provided blood samples for genotyping.ResultsIn line with a hypothesized moderation effect, -174G allele carriers at IL6 had fewer depressive symptoms following interpersonal stress, relative to C/C homozygotes with equal interpersonal stress exposure. However, IL6 genotype did not moderate the effects of non-interpersonal stress exposure (i.e., financial, work and health-related difficulties) on depression. Also in line with hypotheses, the -511C allele in IL1β, previously associated with higher IL-1β expression, was associated with more severe depression following chronic interpersonal stress exposure, relative to T/T homozygotes. Again, the moderating effect was specific to interpersonal stressors and did not generalize to non-interpersonal stress. TNF was not a moderator of the effects of either interpersonal or non-interpersonal stress on later depression outcomes.ConclusionFindings were consistent with the hypothesis that pro-inflammatory genetic variation increases the risk of stress-induced depression. The present results provide evidence of a genetic mechanism contributing to individual differences in depressive symptomatology following interpersonal stress exposure.
Highlights
Depression is moderately heritable and often manifests following exposure to psychosocial stress (Kendler et al, 1995, 2001)
The aim of the present study was to evaluate the interaction of chronic stress with three pro-inflammatory polymorphisms as precipitants of depressive symptoms in young adulthood
We hypothesized that variation at IL6, IL1b and TNF would potentiate the effects of interpersonal stress on the development of depressive symptoms
Summary
Depression is moderately heritable and often manifests following exposure to psychosocial stress (Kendler et al, 1995, 2001). Possession of a G allele at -174 increases expression of IL-6 mRNA and plasma levels of IL-6, following exposure to the stress hormone norepinephrine, and in response to grief in midlife and older adults (Cole et al, 2010; Schultze-Florey et al, 2012). We were interested in examining IL1b (-511C>T, rs16944, Dixon et al, 2007) and TNF (-308G>A, rs1800629, Abraham and Kroeger, 1999; McGuire et al, 1994; Nadel et al, 1996, but see Bayley et al, 2004) as moderators of the stress-depression relationship, based on their association with changes in pro-inflammatory cytokine expression, and preliminary evidence of their relevance to mood symptoms. We were interested in whether genetic moderation would be specific to chronic interpersonal stress, or would generalize to non-interpersonal stressors as well
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