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首页> 外文期刊>Biology of Mood & Anxiety Disorders >Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in lithium-responders one month after treatment initiation
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Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in lithium-responders one month after treatment initiation

机译：治疗开始后一个月，锂应答者中抗凋亡Bcl2基因家族成员的比例增加

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Background Lithium is considered by many as the gold standard medication in the management of bipolar disorder (BD). However, the clinical response to lithium is heterogeneous, and the molecular basis for this difference in response is unknown. In the present study, we sought to determine how the peripheral blood gene expression profiles of patients with bipolar disorder (BD) changed over time following intitiation of treatment with lithium, and whether differences in those profiles over time were related to the clinical response. Methods Illumina Sentrix Beadchip (Human-6v2) microarrays containing?>?48,000 transcript probes were used to measure levels of expression of gene-expression in peripheral blood from 20 depressed subjects with BD prior to and every two weeks during 8?weeks of open-label treatment with lithium. Changes in gene-expression were compared between treatment responders (defined as a decrease in the Hamilton Depression Rating Scale of 50% or more) and non-responders. Pathway analysis was conducted using GeneGO Metacore software. Results 127 genes showed a differential response in responders vs. non-responders. Pathway analysis showed that regulation of apoptosis was the most significantly affected pathway among these genes. Closer examination of the time-course of changes among BCL2 related genes showed that in lithium-responders, one month after starting treatment with lithium, several anti-apoptotic genes including Bcl2 and insulin receptor substrate 2 (IRS2) were up-regulated, while pro-apoptotic genes, including BCL2-antagonist/killer 1 (BAK1) and BCL2-associated agonist of cell death (BAD), were down-regulated. In contrast, in lithium non-responders, BCL2 and IRS2 were down-regulated, while BAK1 and BAD up-regulated at the one-month time-point. Conclusions These results suggest that differential changes in the balance of pro- and anti- apoptotic gene-expression following treatment with lithium may explain some of the heterogeneity in clinical response in BD patients.
机译：背景技术锂被认为是治疗双相情感障碍（BD）的金标准药物。然而，对锂的临床反应是异质的，并且这种反应差异的分子基础是未知的。在本研究中，我们试图确定双相情感障碍（BD）患者开始用锂治疗后其外周血基因表达谱如何随时间变化，以及这些谱随时间的差异是否与临床反应相关。方法使用Illumina Sentrix Beadchip（Human-6v2）芯片，该芯片包含≥48,000个转录探针，用于测量20例BD抑郁患者在开放前8周和每2周中外周血基因表达的水平。用锂进行标签处理。比较了治疗反应者（定义为汉密尔顿抑郁量表降低50％或更多）和无反应者之间基因表达的变化。通路分析是使用GeneGO Metacore软件进行的。结果127个基因在应答者与非应答者中表现出不同的应答。途径分析表明，凋亡调控是这些基因中受影响最大的途径。仔细检查BCL2相关基因之间变化的时程可知，在锂反应者中，开始用锂治疗一个月后，包括Bcl2和胰岛素受体底物2（IRS2）在内的一些抗凋亡基因被上调，而对BCL2相关基因的改变则受到影响。 -凋亡基因，包括BCL2拮抗剂/杀手1（BAK1）和BCL2相关的细胞死亡激动剂（BAD），被下调。相反，在一个锂无响应者中，在一个月的时间点，BCL2和IRS2被下调，而BAK1和BAD被上调。结论这些结果表明，锂治疗后促和抗凋亡基因表达平衡的差异变化可能解释了BD患者临床反应的某些异质性。

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