Scientists Say They ID Depression Gene (2003)

Scientists say they've identified a flawed gene that appears to promote manic-depression, or bipolar disorder, a finding that could eventually help guide scientists to new treatments.

A particular variant of the gene was associated with only about 3 percent of cases in a study, but researchers said other variants might be involved with more.

Follow-up research might help reveal the mysterious underlying biology that makes some people susceptible to the disorder, and so help scientists devise new treatments, said the study's senior author, Dr. John Kelsoe of the University of California, San Diego.

The work is reported in Monday's issue of the journal Molecular Psychiatry.

Previous studies have suggested that other genes are involved in manic-depression. But one expert, Dr. Melvin McInnis of Johns Hopkins University in Baltimore, said in an interview that he thinks Kelsoe's new work and another recent study provide the strongest evidence for involvement of particular genes in the disease.

Manic-depression, which affects about 2.3 million American adults, involves episodes of depression and mania, states of abnormally high mood or irritability.

While effective treatment is available, scientists would like to find better medications.

Genetics clearly play a role. Kelsoe's work focused on a gene called GRK3, which influences the brain's sensitivity to chemical messages brain cells send each other. Defects in the gene might promote manic-depression by making people oversensitive to these messages, which are carried by dopamine and other substances, he said.

Kelsoe and colleagues found statistical evidence tying a particular variant of the GRK3 gene to the disease. They tracked the inheritance of this variant from parent to child in families with a history of bipolar disorder. Overall, the variant was passed along more often than one would expect by chance to a child who later developed the disease.

That suggests the variant promotes susceptibility to bipolar disorder.

The association between the variant gene and the disorder appeared in one group of 153 families and a second group of 275 families. That association is only statistical, and Kelsoe said researchers now are looking for biological evidence that this variant of the gene acts abnormally.

科学家称他们已经发现了一种引发躁郁症，或称双极性疾患的破坏性基因。这项发现可以最终在躁郁症的治疗方面为科学家们提供指导性帮助。

研究者们在研究中发现，仅有3％的病例证实是和此种基因的一种特殊变体有关，但是其他的变体的诱病率可能会更高。

这项研究报告的作者，圣地亚哥的加利福尼亚大学的约翰·凯尔索博士说，今后的深入研究或许可以揭示这种神秘的隐形生物是如何让某些人患上躁郁症的，这样就可以帮助科学家们制定出新的治疗方案。

这项研究刊登在了6月16日的期刊《分子精神病学》上。

从前的研究发现有其他种类的基因同躁郁症的发病有关。但是位于巴尔的摩的约翰斯·霍普金斯大学的梅尔文·麦金尼斯博士，一位研究躁郁症的专家在一次采访中说，他认为凯尔索博士的新研究和近期的其他有关研究都有力地证明这种病同某种特殊的基因有关。

目前美国有230万成年人饱受躁郁症之苦。这种病的症候主要是间歇性的抑郁和狂躁，出现反常的情绪高涨或者兴奋。

尽管我们现在已经有了有效的治疗方法，但是科学家们还在寻求更好的治疗途径。

研究表明，遗传学显然同这种病有关。凯尔索博士的研究集中在一种成为GRK3的基因上。这种基因影响大脑对化学成分和大脑细胞之间相互传递的敏感度。凯尔索博士说，这种基因的特性可以最终造成人们对这些成分（通常在多巴胺和其他物质中）的过分敏感，而诱发躁郁症。 凯尔索博士和同事们已经发现了同GRK3这种特殊基因变体相关的数据证据。他们跟踪研究了有躁郁症病史的家庭中带有这种变体的父母和孩子之间的遗传情况。总的来说，这种变体通常是会由父母遗传给孩子的，而孩子日后自然也会患上躁郁症。

这就说明正是这种变体诱发了躁郁症。

这种基因变体和躁郁症之间的研究结果是在分别对153个家庭和275个家庭进行调查之后得出的。但是目前这个结果还只停留在数据阶段，因此凯尔索博士说研究者们正在寻找证明这种基因变体反常作用的生物学方面的证据。


译者注：

1. 所谓"躁郁症"（manic-depression），一般而言是指个体有时出现抑郁的症状，有时又出现狂躁的症状，此两种特征不断的交互出现之情形，因此又称之为双极性疾患（bipolar disorder），也就是说个体会出现两极的情绪反应，一为狂躁，另一为抑郁。当个体在狂躁阶段，其出现的特征为情绪异常兴奋、自我膨胀，睡眠时数减少，非常健谈、多话，常常是滔滔不绝讲个没完，另外他们的思考或想法也经常跳来跳去，称之为跳跃性思考（flight of ideas），易分心，在行为上我们可以看到其常常疯狂购物，而不管价钱多少等失控行为特征。当个体处于抑郁的阶段，其特征又显示出心情沮丧低沈、对任何事缺乏反应或兴趣、体重改变、产生睡眠困扰、缺乏活力、负向的认知或看法等等的特征。

2. 多巴胺：一种治疗脑神经病的药物