Molecular Genetics of Schizophrenia

精神分裂症是一种严重的精神疾病，影响了大约1%的人口。它的特点是所谓的精神病症状，特别是妄想（错误信念）和幻觉（错误感知），后者通常以幻听的形式出现。患者还往往表现出情绪反应的改变，思维和推理的障碍以及奇怪的行为。症状可以从儿童早期就出现，但通常在十几岁晚期和二十岁早期就有临床可检测的发病。这种发病年龄，再加上许多患者对任何形式的治疗反应都很差，甚至根本没有反应，对于那些有反应的人来说，复发通常很频繁，这意味着这种疾病通常影响到绝大多数人。成人生活。这使得精神分裂症成为患者、其家庭和更广泛社会的主要负担。一个世纪以来，人们已经清楚，精神分裂症是家族遗传的，现在人们知道，这主要是由于基因而不是家庭环境。精神分裂症显然是一种脑部疾病，但尽管进行了大量研究，仍无法确定导致这种疾病的特定脑部异常。这些知识可能是开发真正有效的治疗方法所必需的。我们相信，确定精神分裂症背后的异常的最大希望是确定遗传易感性的本质。这已被证明是困难的，因为精神分裂症像其他常见疾病一样，不是由于单一基因突变而发生的，而是反映了大量基因的运作。风险的基因吗?每一种都只会导致患这种疾病的风险小幅增加。真的是出生时遗传的基因组合决定了一个人吗？年代的风险。现代遗传方法第一次允许一个人的绝大多数变异。他的DNA将在一次实验中被评估。如果这项技术应用于足够多的人，就有可能识别出导致某种疾病风险增加的风险基因，即使是很小的风险增加。这种方法已成功地应用于其他常见疾病，如哮喘、糖尿病、心脏病等。我们建议在我们和我们的合作者多年来收集的大量患者样本中使用类似的方法，正是为了进行这些研究。

Schizophrenia is a severe psychiatric disorder, which affects approximately 1% of the population. It is characterised by so-called psychotic symptoms, in particular delusions (false beliefs) and hallucinations (false perceptions), the latter being often in the form of hearing voices. Sufferers also tend to show altered emotional reactivity, impairments of thinking and reasoning and bizarre behaviour. Signs can be present from early childhood, but usually the disorder has its clinically detectable onset in the late teens and early 20?s. This age of onset, combined with the facts that many patients respond poorly or even not at all to any form of treatment, and for those that do respond, relapse is usually frequent, mean that the illness typically impacts on the vast majority of an individual?s adult life. This makes schizophrenia a major burden on the patient, their family and wider society. It has been clear for a century that schizophrenia runs in families, and this is now known to be largely due to genes rather than the family environment. Schizophrenia is clearly a brain disease but in spite of much research, it has not been possible to identify specific brain abnormalities that cause the disorder. Such knowledge is likely to be required for the development of truly effective treatments. It is our belief that the best hope of identifying the abnormalities that underlie schizophrenia is to identify the nature of the genetic susceptibility. This has proven difficult because schizophrenia, like other common diseases, does not occur as a result of a single genetic mutation, but reflects the operation of a large number of ?risk genes? each of which is responsible for only a small increase in risk of the disorder. It is really the combination of genes inherited at birth that determine someone?s risk. Modern genetic methods are, for the first time, allowing the great majority of variation in a person?s DNA to be assessed in a single experiment. If this technology is applied to a sufficiently large number of people, it is possible to identify risk genes that cause even fairly small increases in risk for a disease. This approach has been successfully applied to other common diseases such as asthma, diabetes, heart disease etc. We are proposing to use similar methods in large samples of patients that we and our collaborators have assembled over many years, precisely with a view to undertaking these studies.