Effects of Lithium Monotherapy for Bipolar Disorder on Gene Expression in Peripheral Lymphocytes.
Effects of Lithium Monotherapy for Bipolar Disorder on Gene Expression in Peripheral Lymphocytes.
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锂单药治疗双相情感障碍对外周淋巴细胞基因表达的影响。
DOI：
10.1159/000446348
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Edenberg,HowardJ
中科院分区：
文献类型：
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作者：
Anand,Amit;McClintick,JeanetteN;Murrell,Jill;Karne,Harish;Nurnberger,JohnI;Edenberg,HowardJ
背景：本研究探讨锂单药治疗对双相情感障碍（BD）外周血淋巴细胞基因表达的影响。方法：对22例无药物治疗的双相情感障碍患者（轻躁狂11例，抑郁症11例）进行锂离子单药治疗。密切匹配的健康受试者（n = 15）被纳入对照组，但未接受治疗。在基线和治疗2周和8周后采集血液RNA样本。使用Affymetrix GeneChip®Human Gene 1.0 ST阵列检测RNA表达，然后进行匠心通路分析。第2周和第8周的对比结果无显著性差异，并予以合并。结果：在BD受试者中，56个基因与基线相比有显著（错误发现率<0.1）的表达变化；在第2周和第8周，所有这些的效应大小和方向相似。其中包括免疫相关基因（IL5RA、MOK、IFI6和RFX2）、嘌呤能受体（P2RY14、P2RY2和ADORA3）和信号转导相关基因（CAMK1和PIK3R6）。通路和上游调控分析也显示，锂改变了一些免疫和信号转导相关的功能。差异表达基因与第8周的临床反应无关，但其他参与蛋白质合成和降解的基因与临床反应相关。结论：外周基因表达可能是锂效应的生物标志物。
Background:This study investigated the effect of lithium monotherapy on peripheral lymphocyte gene expression in bipolar disorder (BD).Method:Twenty-two medication-free bipolar subjects (11 hypomanic, 11 depressed) were started on lithium monotherapy. Closely matched healthy subjects (n = 15) were included as controls but did not receive treatment. Blood RNA samples were collected at baseline and after 2 and 8 weeks of treatment. RNA expression was measured using the Affymetrix GeneChip® Human Gene 1.0 ST Array followed by Ingenuity pathways analysis. The results for the contrast of weeks 2 and 8 were not significantly different and were combined.Results:In BD subjects, 56 genes showed significant (false discovery rate <0.1) expression changes from baseline; the effect sizes and directions for all of these were similar at weeks 2 and 8. Among these were immune-related genes (IL5RA, MOK, IFI6, and RFX2), purinergic receptors (P2RY14, P2RY2, and ADORA3) and signal transduction-related genes (CAMK1 and PIK3R6). Pathway and upstream regulator analysis also revealed that lithium altered several immune- and signal transduction-related functions. Differentially expressed genes did not correlate with week 8 clinical response, but other genes involved in protein synthesis and degradation did.Conclusion:Peripheral gene expression may serve as a biomarker of lithium effect.