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标题: yeeyan组:精神分裂症,双相情感障碍共用一种遗传学原因 [打印本页]

作者: woodmqf    时间: 09-2-10 15:01
标题: yeeyan组:精神分裂症,双相情感障碍共用一种遗传学原因
精神分裂症,双相情感障碍共用一种遗传学原因

Caroline Cassels

2009年1月21日

已经进行的最大规模双相情感障碍精神分裂症的家族研究显示这两种疾病共用一种遗传学原因。这项研究推翻了当前流行的观点,认为两种疾病是相互独立且是不同的。

这项研究覆盖了来自于超过200万家庭多于900万的个体,横跨30个年龄段,它说明患有精神分裂症(35985名)或双相情感障碍(40487名)的个体,一级亲属有明显更大的风险得这些疾病。

瑞典斯德哥尔摩卡洛林斯卡学院的研究者发现父母患病所有兄妹得精神分裂症是普通人群的9倍,而得双相情感障碍是8倍。同母异父兄妹得精神分裂症是普通人群的3.6倍,双相情感障碍是4.5倍。

对于同父异母兄妹这种几率更低,得精神分裂症是普通人群的2.7倍,得双相情感障碍是2.4倍。

“我们的结果相当清楚,表明精神分裂症和双相情感障碍在一级亲属的患病风险都是相当高的。”研究调查者Christina Hultman博士告诉MedscapePsychiatry记者。“也有明显的来自异姓兄妹和收养亲属的证据表明风险应该基本上是由于遗传因素而不是环境因素引起的。这使我们认为在这两种精神疾病间有共同的遗传变异。”Hultman继续说到。

这项研究在1月17日的《柳叶刀》上发表。

厚实的发现

虽然传统上,根据不同的症状标准和治疗方法,精神分裂症和双相情感障碍是划为两个不同的疾病,但是,过去十年间很多分子遗传学的研究结果假设这两种疾病可能共用基因。虽然这些发现并非确定无疑,但是Hultman博士和她的同事们觉得他们进一步的研究是正当合理的。

为了检查是否这两种疾病有基因上的关联,研究者建立两个瑞典国民档案的数据连接——一个国家的家族谱系记录和一个国家出院记录(包括所有公开的精神病住院病人准入许可)。

虽然,研究者怀疑这两种疾病存在普遍的遗传联系,但是Hultman博士说大量共享的遗传影响仍令他们惊讶。

研究者也发现个体患有双相情感障碍,那么其所有亲属都会有更高的风险患精神分裂症,包括那些亲生父母患病的收养子。

环境作用小但至关重要

精神分裂症和双相情感障碍的全部遗传可能性分别为64%和59%。同时患有两种病的概率是63%,是由他们的基因特性决定。

共有的环境影响不大,但却是很可观——对精神分裂症贡献4.5%,双相情感障碍4.4%-7%,两者皆有为2.3%-6.2%

依照Hultman博士的说法,这些结果说明某个家庭成员患有任一这些情感障碍都会提高整体的患病风险,因而说明这主要是由于遗传因素影响的结果与共有的环境因素关系不大。

下一步研究包括证实这些发现以及在这些患者中进行分子遗传学研究来识别两种疾病共用的基因。“如果我们能发现这些基因而且能理解它们的生物学功能,这将最终导致更好的治疗效果。”她说。

虽然做出肯定的临床推荐还为时过早,但是研究者和生理学家应该在研究或/和治疗精神分裂症和双相情感障碍时考虑这个普遍的遗传学背景。

当前的医学分类是“错误的”

在编后语中,英国皇家精神病学院, 卡迪夫大学Michael Owen博士和Nick Craddick博士认为这项研究清楚地解释了精神分裂症和双相情感障碍患者的一级亲属有更高的风险得这两种病,并且主要是遗传因素导致的。

他们补充说当前把这些疾病作为无关、自然的疾病实体的分类是错误的,其中包括美国精神疾病协会的精神障碍诊断与统计手册(DSM)和世界健康组织的国际疾病分类手册(ICD)。

“这种共有的基因的信念幸存了下来,尽管事实上,虽然典型的精神分裂症和双相情感障碍是常见的,但是许多病人在病程中都有精神病和情感上的症状并且在不同时候得到两种诊断是很平常的”他们写到。

Owen和Craddock博士已经努力开始修订DSM和ICD手册了,他们总结说这个新的诊断标准“促进精细的疾病测量和对精神病理学的重新评估……最终的临床诊断将允许当前和未来的疗效可以在患者中监控,更好的整合研究于病因,分类与治疗中。”

瑞典国科会工作生活与社会研究委员会和瑞典研究会提供支持。作者报道无价值取向。

《柳叶刀》 2009;373:234-239 摘要,190-191摘要

Schizophrenia, Bipolar Disorder Share Common Genetic Cause
Caroline Cassels

January 21, 2009 — The largest family study of schizophrenia and bipolar disorder ever conducted shows that these 2 disorders share a common genetic cause, a finding that challenges the current view that they are separate and distinct conditions.
The analysis, which included more than 9 million individuals from more than 2 million families over a 30-year period, showed that first-degree relatives of individuals with either schizophrenia (35,985 individuals) or bipolar disorder (40,487) had a significantly increased risk for these disorders.
Investigators at the Karolinksa Institutet, in Stockholm, Sweden, found that full siblings were 9 times more likely than the general population to have schizophrenia and 8 times more likely to have bipolar disorder. Maternal half-siblings were 3.6 times more likely to have schizophrenia and 4.5 times more likely to have bipolar disorder than the general population.
This risk was lower for paternal half-siblings, who were 2.7 times more likely to have schizophrenia and 2.4 times more likely to have bipolar disorder.
"Our results were fairly clear-cut and demonstrated that there was a significant increased risk of both schizophrenia and bipolar disorder among first-degree relatives with either of these diseases," study investigator Christina Hultman, PhD, told Medscape Psychiatry. "There was also evidence from the half-siblings and adoptive relatives that this risk is substantially due to genetic factors vs environmental factors, which allows us to conclude that there is a common genetic variation between these 2 psychotic disorders," Dr. Hultman added.
The study is published in the January 17 issue of the Lancet.
Findings Robust
Although traditionally schizophrenia and bipolar disorder have been classified as 2 distinct diseases with different diagnostic criteria and treatment paths, within the past decade results from several molecular genetic studies have suggested that the disorders may share common genes. While these findings were not definitive, Dr. Hultman and her colleagues felt they warranted further investigation.
To examine whether there was a genetic association between the 2 disorders, the investigators linked data from 2 Swedish national registries — a multigenerational national register and a national hospital discharge register, which includes data on all public psychiatric inpatient admissions.
While the investigators suspected there was a common genetic link between the 2 disorders, Dr. Hultman said they were surprised by the magnitude of the shared genetic effect.
Investigators also found that among relatives of individuals with bipolar disorder, there was an increased risk for schizophrenia for all relationships, including adopted children to their biological parents.
Environmental Effects Small but Substantial
Overall heritability for schizophrenia and bipolar disorder was 64% and 59%, respectively. The comorbidity between disorders was 63% and mainly due to additive genetic effects common to both disorders.
Shared environmental effects were small, but substantial — 4.5% for schizophrenia, 4.4% to 7% for bipolar disorder, and 2.3% to 6.2% for both disorders.
According to Dr. Hultman, these results demonstrate that members of families in which someone has either of these affective disorders run an increased risk of developing the same condition and that this is chiefly the result of genetic factors, with only a slight influence of shared environmental factors.
Next research steps include confirmation of these findings and conducting molecular genetic studies in these patients to identify the genes common to both disorders. "If we find these genes and are able to understand their biological function, this could ultimately lead to better treatment," she said.
While it is still too early to make firm clinical recommendations, researchers and physicians should consider this common genetic background when researching and/or treating schizophrenia and bipolar disorder.
Current Classification "Erroneous"
In an accompanying editorial, Michael Owen, PhD, FRCPsych, and Nick Craddick, PhD, FRCPsych, from the University of Cardiff, in the United Kingdom, say the study's findings clearly demonstrate that first-degree relatives of individuals with schizophrenia or bipolar disorder are at increased risk for both disorders and that this is mainly due to genetic factors.
They add that the current classification of these disorders in both the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM) and the World Health Organization's International Classification of Diseases (ICD) as discrete, natural disease entities is erroneous.
"This belief has survived despite the fact that, although typical schizophrenia and bipolar disorder are often seen, many patients have both psychotic and affective symptoms over the course of their illnesses and it is not uncommon for patients to receive both diagnoses at different times," they write.
With efforts well under way to revise the DSM and ICD, Drs. Owen and Craddock conclude that the new diagnostic criteria "encourage the careful measurement and reappraisal of psychopathology. . . . The resulting clinical diagnosis will allow the efficacy of current and future treatments to be monitored in individuals and better serve research into cause, classification, and treatment."
The study was supported by the Swedish Council for Working Life and Social Research and the Swedish Research Council. The authors report no conflicts of interest.
Lancet. 2009;373:234-239 Abstract, 190-191. Abstract


拍砖 这边走:http://www.yeeyan.com/articles/view/61461/28187

[ 本帖最后由 woodmqf 于 09-2-10 17:26 编辑 ]
作者: woodmqf    时间: 09-2-10 17:05
标题: 转帖:精神与情感:一对姐妹花?董欢霁
  有研究者发现双相情感障碍与精神分裂症之间存在共同的遗传潜质,认为不能将两者绝对独立地看待
  说起双相情感障碍,或者说是躁狂和抑郁这类情绪变化,很多人可能会想起艺术家梵高和舒曼;谈到精神分裂症,几年前奥斯卡获奖影片《美丽心灵》中主角的原型——诺贝尔经济学奖获得者约翰·纳什已让这一疾病名称众所周知。而此两种看似独立的疾病,在遗传背景中是否会存在一定的相关性?这已成为精神病医生之间的一个旷日持久的议题。
  随着研究的不断深入,瑞典卡罗林斯卡医学院Paul Lichtenstein博士最近发表的一篇论文或许离问题的答案又近了一步。在对900万瑞典公民进行调查后,Lichtenstein博士课题组得出的结论是,两种疾病存在遗传相似性。精神分裂症病人罹患双相情感障碍的风险增加;反之,双相情感障碍病人的子女和其同胞(兄弟姐妹)患精神分裂症的危险性高。他的这一研究结果发表在近期出版的《柳叶刀》(Lancet)上。
  
  数据说出事实  
  Lichtenstein博士课题组的数据来自于900万瑞典公民中的200万个家庭,调查涵盖到患者的一级亲属系。研究总共调查了35,985名符合精神分裂症诊断标准和40,487名双相情感障碍的患者。在这其中,有2543名患者属于同时符合这两种疾病的诊断。研究者再从瑞典国家健康卫生中心调研了患者一级亲属的子女及其同胞(兄弟姐妹),以及被收养子女及其同胞。
  数据显示,精神分裂症患者的子嗣或其同胞分别有5.2(95%可信区间:4.4~6.2)和3.7(95%可信区间:3.2~4.2)的罹患双相情感障碍的风险。而在双相情感障碍患者中,其子女和同胞患上精神分裂症的风险分别是2.4(95%可信区间:2.1~2.6)和3.9(95%可信区间:3.4~4.4)。
  精神分裂症患者的一级亲属有着罹患同样疾病的高风险性(其子女的相对危险性为9.9,95%可信区间:8.5~11.6;同胞的相对危险性为9.0,95%可信区间:8.1~9.9)。同样,双相情感障碍患者一级亲属的患病风险同样很高(其子女的相对危险性为6.4, 95%可信区间:5.9~7.1; 同胞的相对危险性为7.9, 95%可信区间:7.1~8.8)。根据以往的研究,这些结果对研究者而言并不出乎意外。
  研究小组对患者收养的子女及其同胞(被收养,与患者无血缘关系)也做了相关的调查。对被收养的子女或同胞而言,其患病的绝对风险与该家族中的同辈(与患者有血缘关系)程度相近,但也发现并不是所有的这类情况中其比值都有统计学意义。如果被收养的子女和同胞的亲生父母没有精神疾病,则他们罹患该病的风险并不增加。
  再者,在父系患病的同胞中,研究者发现其患病风险也要小幅高于母系患病的同胞。
  基于上述这些数据,Lichtenstein博士课题组拟出了这样一个比例,表明个体基因与成长环境对患者发病风险的影响程度:
  精神分裂症——
  ★累积基因遗传效应:64.3%(95%可信区间:61.7%~67.5%)
  ★幼年期的环境影响:4.5%(95%可信区间:4.4%~7.4%)
  ★非环境影响: 31.1% (95%可信区间:25.1%~33.9%)
  双相情感障碍——
  ★累积基因遗传效应: 58.6%(95%可信区间:56.4%~61.8%)
  ★幼年期的环境影响:3.4% (95%可信区间:2.3%~6.2%)
  ★非环境影响:38.0% (95%可信区间:28.7%~32.3%)
  
  研究推动实践  
  Lichtenstein博士在论文中分析说,他们这次调查所发现的遗传倾向率要比那些针对双胞胎的研究低,这可能是因为家族性研究更着重于年龄和非附加基因遗传效应的差异性。而此次的研究之所以有重大意义,是因为研究者成功地发现了两种原本完全独立的精神疾病之间存在共同的遗传潜质,发现了并不能将两者绝对独立地看待。
  “精神分裂症和双相情感障碍有某些共同的致病基因存在,但是这一遗传并不完全等同。”研究者强调了这一点,“不管是精神分裂症还是双相情感障碍,都可能存在一定比例上的基因变异现象,这和其他疾病一样。”
  因此,某些基因可能是这两种疾病的共同致病基因,而某些基因则可能只针对特定一种疾病。分子遗传学、解剖学,以及对一定数量的存在这两种疾病症状的患者进行的研究结论,都证实了两者共同的病因源头。
  在此之前,已经有一些研究者称并没有发现这两种疾病患者的家族中存在基因重叠或风险增加的情况。由此,美国威尔士州Cardiff 大学的Michael Owen博士和Nick Craddock医生在Lichtenstein博士的论文后附加了述评,认为“这一研究提示我们,可能是撇开对双相情感障碍与精神分裂症做独立诊断的时候了”。
  Owen和 Craddock撰文说:“现在有一种普遍的却是错误的看法,认为双相情感障碍与精神分裂症这两种疾病是完全分开的、独立的疾病,最近的诊疗常规中认定它们有着各自不同的病理特征。这一常规之所以成立,是因为典型的双相情感障碍或精神分裂症都很常见,但是仍然有很多患者存在精神上和情感上的双重症状,而在这些症状出现的不同时间并不容易得到及时正确的诊断。”
  考虑到本领域的诊断与统计手册(DSM)和国际疾病分类法(CDS)正处于修改程序中,Owen和Craddock建议,“新的诊断标准应更谨慎地修定诊断名称,还要考虑对精神病理学做重新评估,从而更妥善地做好疾病诊断的分类”。
  
  Tips:  
  双相情感障碍(bipolar disorders)——又叫躁狂抑郁症,主要表现为情感高涨(躁狂)或低落(抑郁),或两者交替出现。早期先兆为双相性性格变异,多呈循环特点,情感变化经常不明原因地“两极分化”,若发展为进行性的、典型性的情感两极分化,主要特征为情感障碍。
  精神分裂症(schizophrenia)——基本个性改变,思维、情感、行为的分裂,精神活动与环境的不协调为主要特征的一类最常见的精神病。主要症状有:神经症样症状,人格改变,情感改变和感知思维障碍等。


作者: 遭遇躁郁之后    时间: 09-2-10 18:29
有道理
作者: 温州抑郁了    时间: 14-3-23 20:28

作者: 现在168    时间: 14-3-23 21:43
本帖最后由 现在168 于 14-3-23 21:46 编辑

该病具有复杂的遗传结构,遗传度在80%到85%之间;同时,该病经常与精神分裂症和重度抑郁症具有一些相似的临床特征,存在一定的共发性及共同的遗传因素。

精神分裂症和BPD的遗传率分别为64%和59%。

两种疾病共有的环境因素较少,但具有实质性意义(精神分裂症4.5%,BPD3.4%)。

共病主要归咎于两种疾病共同的基因叠加效应(63%)
作者: 智空    时间: 14-3-24 10:30
哦。这样子啊




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