Synapsin II Is Involved in the Molecular Pathway of Lithium Treatment in Bipolar Disorder
Synapsin II Is Involved in the Molecular Pathway of Lithium Treatment in Bipolar Disorder
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DOI：
10.1371/journal.pone.0032680
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发表时间：
2012-02-24
期刊：
影响因子：
3.7
通讯作者：
Turecki, Gustavo
中科院分区：
文献类型：
--
作者：
Cruceanu, Cristiana;Alda, Martin;Turecki, Gustavo
双相情感障碍 (BD) 是一种使人衰弱的精神疾病，在普通人群中的患病率为 1-2%，其特征是情绪的严重间歇性变化，从抑郁发作到躁狂发作。最常见的治疗方法之一是锂 (Li)，30-60% 的患者获得成功缓解。突触蛋白 II (SYN2) 是一种神经元磷蛋白，我们之前在一项全基因组连锁研究中将其确定为 BD 病因和/或对 Li 治疗反应的可能候选基因，该研究重点关注对 Li 预防具有良好反应的 BD 患者。在本研究中，我们研究了该基因在 BD 中的作用，特别是与 Li 治疗有关。我们研究了锂治疗对具有优异锂反应者、无反应者以及非精神病对照患者的淋巴母细胞系中 SYN2 表达的影响。最后，我们试图确定Li是否对神经元衍生细胞系中的基因表达具有细胞类型特异性的影响。在这两个体外模型中，我们发现 SYN2 受到 Li 的存在的调节。通过关注锂离子反应 BD，我们已经确定了一些患者锂离子反应的潜在机制。
Bipolar disorder (BD) is a debilitating psychiatric condition with a prevalence of 1-2% in the general population that is characterized by severe episodic shifts in mood ranging from depressive to manic episodes. One of the most common treatments is lithium (Li), with successful response in 30-60% of patients. Synapsin II (SYN2) is a neuronal phosphoprotein that we have previously identified as a possible candidate gene for the etiology of BD and/or response to Li treatment in a genome-wide linkage study focusing on BD patients characterized for excellent response to Li prophylaxis. In the present study we investigated the role of this gene in BD, particularly as it pertains to Li treatment. We investigated the effect of lithium treatment on the expression of SYN2 in lymphoblastoid cell lines from patients characterized as excellent Li-responders, non-responders, as well as non-psychiatric controls. Finally, we sought to determine if Li has a cell-type-specific effect on gene expression in neuronal-derived cell lines. In both in vitro models, we found SYN2 to be modulated by the presence of Li. By focusing on Li-responsive BD we have identified a potential mechanism for Li response in some patients.