Tartter Margaret, Hammen Constance, Bower Julienne E, Brennan Patricia A, Cole Steven
Department of Psychology, University of California, Los Angeles, USA.
Department of Psychology, University of California, Los Angeles, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, USA.
Brain Behav Immun. 2015 May;46:104-11. doi: 10.1016/j.bbi.2015.01.003. Epub 2015 Jan 13.
Close 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.
Participants were 444 Australian youth (mean age=20.12) whose exposure to chronic stress in the past 6months 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.
In 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.
Findings 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.
近三分之一的重度抑郁症患者表现出促炎细胞因子增加，而这又与炎症性疾病风险相关。因此，增强免疫反应性的基因变异可能会增强对压力的炎症和抑郁反应。本研究的目的是调查白细胞介素6（IL6）（-174G>C，rs1800795）、白细胞介素1β（IL1β）（-511C>T，rs16944）和肿瘤坏死因子（TNF）（-308G>A，rs1800629）启动子区域的三个功能性单核苷酸多态性（SNP），作为慢性应激暴露与抑郁症状升高之间关系的调节因素。
参与者为444名澳大利亚青年（平均年龄=20.12岁），他们过去6个月的慢性应激暴露情况通过半结构化的加州大学洛杉矶分校生活应激访谈进行评估，并在15岁和20岁时完成贝克抑郁量表第二版。在22岁至25岁之间，所选样本中的所有参与者都提供了血样进行基因分型。
与假设的调节效应一致，相对于人际压力暴露相同的C/C纯合子，IL6基因-174G等位基因携带者在人际压力后抑郁症状较少。然而，IL6基因型并未调节非人际压力暴露（即财务、工作和健康相关困难）对抑郁的影响。同样与假设一致，IL1β基因中先前与较高IL-1β表达相关的-511C等位基因，相对于T/T纯合子，在慢性人际压力暴露后与更严重的抑郁相关。同样，调节效应特定于人际压力源，并不适用于非人际压力。TNF不是人际或非人际压力对后期抑郁结果影响的调节因素。
研究结果与促炎基因变异增加应激诱导抑郁症风险的假设一致。目前的结果提供了一种遗传机制的证据，该机制导致人际压力暴露后抑郁症状的个体差异。
