Institute for Policy Research, Northwestern University, United States.
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, United States; Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, United States.
Brain Behav Immun. 2019 Aug;80:163-169. doi: 10.1016/j.bbi.2019.03.004. Epub 2019 Mar 6.
Rates of depression increase and peak during late adolescence and alterations in immune processes are thought to be both a risk factor and outcome of depression. However, few studies have examined depression-immune dynamics among adolescents. Using a functional genomics approach, the current study examined whether depressive symptoms were associated with activation of a gene expression profile, characterized by upregulated expression of pro-inflammatory-related genes and downregulated expression of antiviral-related genes in a sample of older adolescents (M = 18.37, SD = 0.51).
Participants (n = 87) reported on their depressive symptoms during the past week using the CES-D, and provided blood samples for genome-wide transcriptional profiling of mRNA.
Adolescents with clinically-significant levels of depressive symptoms (CES-D ≥ 16) exhibited upregulated expression of inflammation-related genes and downregulated expression of antiviral-related genes compared to their peers with lower levels of depressive symptoms (CES-D < 16). Bioinformatics analyses suggested that this pattern of differential gene expression was mediated by greater activity of the pro-inflammatory transcription factor, nuclear factor-kappa B (NF-κB), and reduced activity of glucocorticoid receptors (GRs) and interferon response factors (IRFs). Additional analyses implicated monocytes, B cells, and dendritic cells as primary cellular sources of the observed gene expression patterns associated with depressive symptoms.
Results are consistent with past work demonstrating links between depression and altered immunity. They provide a molecular basis for these associations and suggest that the underlying molecular signature may emerge as early as late adolescence when rates of depression tend to increase.
抑郁症的发病率在青少年晚期增加并达到高峰，免疫过程的改变被认为既是抑郁症的风险因素，也是其结果。然而，很少有研究检查过青少年的抑郁与免疫动态。本研究采用功能基因组学方法，考察了在一个年龄较大的青少年样本中（M=18.37，SD=0.51），抑郁症状是否与一种基因表达谱的激活有关，这种基因表达谱的特征是促炎相关基因的表达上调和抗病毒相关基因的表达下调。
参与者（n=87）使用 CES-D 在过去一周报告他们的抑郁症状，并提供血液样本进行 mRNA 的全基因组转录谱分析。
与抑郁症状水平较低的同龄人（CES-D<16）相比，具有临床显著水平抑郁症状（CES-D≥16）的青少年表现出炎症相关基因的表达上调和抗病毒相关基因的表达下调。生物信息学分析表明，这种差异基因表达模式是由促炎转录因子核因子-κB（NF-κB）的活性增加和糖皮质激素受体（GRs）和干扰素反应因子（IRFs）的活性降低介导的。进一步的分析表明，单核细胞、B 细胞和树突状细胞是与抑郁症状相关的观察到的基因表达模式的主要细胞来源。
研究结果与过去证明抑郁与免疫改变之间存在联系的工作一致。它们为这些关联提供了分子基础，并表明潜在的分子特征可能早在青少年晚期就出现，此时抑郁的发病率往往会增加。
