Department of Psychiatry, and Depression Clinical Research Centre, Chonnam National University Medical School, Gwangju, Korea.
Neurobiol Aging. 2013 Jan;34(1):356.e1-9. doi: 10.1016/j.neurobiolaging.2012.01.111. Epub 2012 Aug 22.
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. In a 2-year prospective study of a community sample of 521 older people, information on number of physical disorders, diagnosis of depression (Geriatric Mental State), and genotypes for 6 pro-inflammatory (tumor necrosis factor-α -850C/T and -308G/A, interleukin (IL)-1β -511C/T and +3953C/T, IL-6 -174G/C, IL-8 -251T/A) and 2 anti-inflammatory (IL-4 +33T/C, IL-10 -1082G/A) cytokine polymorphisms were ascertained. Total numbers of potential risk alleles were calculated for pro- and anti-inflammatory cytokine genes. Interactions between baseline physical disorders and cytokine genotypes were investigated for incident 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.
炎症细胞因子与抑郁症的病理生理学有关，可能是其与更差的身体健康状况相关的基础。细胞因子的产生受几种多态性的转录活性影响。我们假设与更高的促炎和/或更低的抗炎细胞因子产生相关的等位基因将增强身体障碍与晚年抑郁症之间的关联。在一项对 521 名老年人社区样本的 2 年前瞻性研究中，我们记录了身体障碍的数量、抑郁症的诊断（老年精神状态）以及 6 种促炎（肿瘤坏死因子-α-850C/T 和-308G/A、白细胞介素 (IL)-1β-511C/T 和 +3953C/T、IL-6-174G/C、IL-8-251T/A）和 2 种抗炎（IL-4+33T/C、IL-10-1082G/A）细胞因子多态性的基因型。计算了促炎和抗炎细胞因子基因的潜在风险等位基因总数。研究了基线身体障碍与细胞因子基因型之间的相互作用与新发抑郁症的关系。在存在与更高的促炎细胞因子产生相关的 2 个等位基因（肿瘤坏死因子-α-850T 和 IL-8-251A）和 1 个与抗炎细胞因子产生较低相关的等位基因（IL-4+33C）的情况下，身体障碍与新发抑郁症之间存在显著关联。除了上述 3 个单核苷酸多态性外，还发现了促炎和抗炎细胞因子基因上的总风险等位基因数与总风险等位基因数之间存在独立于所有协变量的显著基因-环境相互作用。这些发现支持了炎症细胞因子介导的炎症途径是身体健康状况恶化与晚年抑郁症之间公认关联的基础，并且为这种关联的遗传基础提供了新的证据。
