A glycogen synthase kinase 3-β promoter gene single nucleotide polymorphism is associated with age at onset and response to total sleep deprivation in bipolar depression
A glycogen synthase kinase 3-β promoter gene single nucleotide polymorphism is associated with age at onset and response to total sleep deprivation in bipolar depression
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DOI：
10.1016/j.neulet.2004.06.050
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发表时间：
2004-09-23
影响因子：
2.5
通讯作者：
Smeraldi, B
中科院分区：
文献类型：
--
作者：
Benedetti, F;Serretti, A;Smeraldi, B
驱动下丘脑视交叉上核生物钟的分子机制可能在情绪障碍中发挥作用。位于糖原合成酶激酶3-β（GSK 3-β）基因有效启动子区（nt-171至+29）的单核苷酸多态性（SNP）（-50 T/C）与双相情感障碍发病的不同年龄有关。GSK 3-β编码一种酶，它是锂和丙戊酸作用的靶点，抑制它会导致临床前模型中的抗抑郁样行为，我们研究了这种多态性对60例抑郁双相I型住院患者对完全睡眠剥夺的急性反应的影响。GSK 3-β启动子突变等位基因（-50 T/C）SNP的纯合子显示双相情感疾病的发病较晚，TSD治疗对感知情绪的急性效应较好（根据VAS评分）。总体而言，这些观察结果表明，这种基因型在双相情感障碍方面具有保护作用。结果证明，与双相情感障碍的可能内在表型的分子时钟相关的基因变体，以及GSK 3-β作为一类新的抗抑郁药物的靶点，但是，在解释这些初步结果时应谨慎，并且必须等待未来的重复研究，因为研究人群中的GSK 3-β *C/C基因型。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
The molecular mechanisms driving the biological clock in the suprachiasmatic nucleus of the hypothalamus may play a role in mood disorders. A single nucleotide polymorphism (SNP) (-50 T/C) falling into the effective promoter region (nt -171 to +29) of the gene coding for glycogen synthase kinase 3-beta (GSK3-beta) has been linked with different age at onset of bipolar illness. GSK3-beta codes for an enzyme which is a target for the action of lithium and valproic acid, and the inhibition of which causes antidepressant-like behaviors in a preclinical model.We studied the effect of this polymorphism on the acute response to total sleep deprivation of 60 depressed bipolar type I inpatients. Homozygotes for the mutant allele of GSK3-beta promoter (-50 T/C) SNP showed a later onset of bipolar illness, and better acute effects of TSD treatment on perceived mood (as rated on VAS). Overall, these observations suggest a protective role for this genotype in respect to bipolar illness.Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, and for GSK3-beta as a target of a new class of antidepressant drugs, but caution ought to be taken in interpreting these preliminary results and future replication studies must be awaited because of the low frequency of the GSK3-beta*C/C genotype in the studied populations. (C) 2004 Elsevier Ireland Ltd. All rights reserved.