Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan; Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, 187-8553, Japan.
DNA Chip Research Inc, Tokyo, 105-0022, Japan.
J Psychiatr Res. 2018 Sep;104:202-210. doi: 10.1016/j.jpsychires.2018.08.010. Epub 2018 Aug 6.
Etiology of depression and its vulnerability remains elusive. Using a latent profile analysis on dimensional personality traits, we previously identified 3 different phenotypes in the general population, namely stress-resilient, -vulnerable, and -resistant groups. Here we performed microarray-based blood gene expression profiling of these 3 groups (n = 20 for each group) in order to identify genes involved in stress vulnerability as it relates to the risk of depression. Identified differentially expressed genes among the groups were most markedly enriched in ribosome-related pathways. These ribosomal genes, which included ribosomal protein L17 (RPL17) and ribosomal protein L34 (RPL34), were upregulated in relation to the stress vulnerability. Protein-protein interaction and correlational co-expression analyses of the differentially expressed genes/non-coding RNAs consistently showed that functional networks involving ribosomes were affected. The significant upregulation of RPL17 and RPL34 was also observed in depressed patients compared to healthy controls, as confirmed in 2 independent case-control datasets by using pooled microarray data and qPCR experiments (total number of subjects was 122 and 166, respectively). Moreover, the upregulation of RPL17 and RPL34 was most marked in DSM-IV major depressive disorder, followed by in bipolar disorder, and then in schizophrenia, suggesting some diagnostic specificity of these markers as well as their general roles in stress vulnerability. These results suggest that ribosomal genes, particularly RPL17 and RPL34, can play integral roles in stress vulnerability and depression across nonclinical and clinical conditions. This study presents an opportunity to understand how multiple psychological traits and underlying molecular mechanisms interact to render individuals vulnerable to depression.
抑郁的病因及其易感性仍然难以捉摸。我们之前使用维度人格特质的潜在剖面分析，在普通人群中确定了 3 种不同的表型，即应激弹性、应激易感性和应激抵抗组。在这里，我们对这 3 组人群（每组 20 人）进行了基于微阵列的血液基因表达谱分析，以鉴定与抑郁风险相关的应激易感性相关的基因。在组间差异表达的基因最显著地富集在核糖体相关途径中。这些核糖体基因，包括核糖体蛋白 L17（RPL17）和核糖体蛋白 L34（RPL34），与应激易感性相关上调。差异表达基因/非编码 RNA 的蛋白质-蛋白质相互作用和相关共表达分析一致表明，涉及核糖体的功能网络受到影响。与健康对照组相比，在抑郁患者中也观察到 RPL17 和 RPL34 的显著上调，这在使用汇集微阵列数据和 qPCR 实验的 2 个独立病例对照数据集（受试者总数分别为 122 和 166）中得到了证实。此外，RPL17 和 RPL34 的上调在 DSM-IV 重性抑郁障碍中最为明显，其次是双相情感障碍，然后是精神分裂症，这表明这些标志物具有一些诊断特异性以及它们在应激易感性中的一般作用。这些结果表明，核糖体基因，特别是 RPL17 和 RPL34，可以在非临床和临床条件下在应激易感性和抑郁中发挥整体作用。这项研究提供了一个机会来了解多种心理特征和潜在的分子机制如何相互作用，使个体易患抑郁症。
