Summaries from the XIX World Congress of Psychiatric Genetics, Washington, DC, September 10-14, 2011.
Summaries from the XIX World Congress of Psychiatric Genetics, Washington, DC, September 10-14, 2011.
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DOI：
10.1002/ajmg.b.32017
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发表时间：
2012-01
影响因子：
2.8
通讯作者：
Delisi, Lynn E
中科院分区：
文献类型：
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作者：
Dai, Nan;Foldager, Leslie;Gallego, Juan A;Hack, Laura M;Ji, Yuan;Lett, Tristram A P;Liu, Bao-Cheng;Loken, Erik K;Mandelli, Laura;Mehta, Divya;Power, Robert A;Sprooten, Emma;Stephens, Sarah H;Paska, Alja Videtic;Yan, Jia;Zai, Clement C;Zai, Gwyneth;Zhang-James, Yanli;O'Shea, Anne;Delisi, Lynn E
自杀与重大情感障碍密切相关，患者完成自杀的风险比一般人群高6至15倍。锂是迄今为止治疗双相情感障碍（BD）最有效的药物，对自杀具有良好的保护作用。然而，导致这些临床效果的机制尚不清楚。到目前为止，有几项研究试图确定与自杀有关的生物标记和基因。Sequeira等人（2006）利用死后脑组织进行的基因表达微阵列研究报告称，与对照组相比，有或没有抑郁症的自杀未遂者中编码亚精胺/精胺n1 -乙酰转移酶1 （SSAT1）的基因表达显著减少。这一结果已被其他人复制。为了证实和扩展这些发现，我们测量了两个以自杀行为为特征的BD受试者和健康对照者的两个人群（撒丁岛人，n = 41和加拿大人，n = 24）淋巴母细胞样细胞系（LCLs）中SSAT1基因的表达水平。为了检测锂对SSAT1的影响，将每个LCL分为2个系，分别在1.0 mmol/l的含锂和不含锂培养基中培养7 d。SSAT1的表达在来自对照组的LCLs中显著增加（p< 0.001），在自杀个人和遗传风险低（p< 0.001）和高（p< 0.001）的LCLs中显著增加（p< 0.05），但在来自自杀完成者的LCLs中没有（p< 0.05）。这些发现在加拿大样本中得到了重复，对合并数据集的分析增加了我们发现的力量和意义。与基因表达结果相反，蛋白质研究表明，在将自杀风险不同的3组与对照组进行比较时，SSAT1水平显著降低。这可能提示多胺系统通路中存在代偿作用。这些差异在体外锂处理后减少或消失。另一方面，在体外进行锂治疗或不进行锂治疗的不同自杀风险组的比较中，没有显示出差异。蛋白质组分析还强调了几种蛋白质在至少一种比较或根据锂处理中表达差异。目前正在鉴定这些蛋白质，结果将在会议上公布。总之，我们的研究结果表明，自杀未遂者可能代表了SSAT1功能改变的一组独特的患者。
Suicide is strongly associated with Major Affective Disorders with a risk for completed suicide 6 to 15 times higher in patients compared to the general population. Lithium is to date the most effective treatment for bipolar disorder (BD) with a well established protective effect against suicide. However, the mechanisms responsible for these clinical effects remain unclear. So far, several studies attempted to identify biological markers and genes involved in suicide. A gene expression microarray study performed using postmortem brain tissue by Sequeira et al. (2006) reported a significant reduction in expression of the gene encoding the enzyme spermidine/spermine N1-acetyltransferase 1 (SSAT1) in suicide completers with and without depression compared to controls. This result has been replicated by others. To confirm and extend these findings, we measured SSAT1 gene expression levels in lymphoblastoid cell lines (LCLs) from two populations (Sardinian, n = 41 and Canadian, n = 24) of BD subjects characterized for suicidal behaviour and healthy controls. In order to test the effect of lithium on SSAT1, each LCL was divided into two lines cultured for 7 days in media with and without LiCl (1.0 mmol/l). SSAT1 expression was significantly increased by lithium in LCLs from controls (p< 0.001) and in subjects with low (p < 0.001) and high (p < 0.001) personal and genetic risk of suicide but not in LCLs from suicide completers (p > 0.05). These findings were replicated in the Canadian sample and the analysis on the pooled dataset increased the power and the significance of our findings. In contrast with the gene expression findings the protein study showed that SSAT1 levels were significantly decreased when comparing each of the 3 groups at different risk of suicide with controls. This could suggest a compensatory effect in the pathway of polyamine system. These differences were reduced or disappeared by lithium treatment in vitro. On the other hand, no differences were shown when comparing groups with different risk of suicide either with or without lithium treatment in vitro. The proteome analysis also highlighted several proteins differentially expressed in at least one of the comparisons or according to lithium treatment. These proteins are currently being identified and results will be presented at the conference. In conclusion, our findings suggest that suicide completers might represent a distinct group of patients with an altered SSAT1 function.