孤獨癥病因的新發現

　　孤獨癥患者的大腦中究竟哪里出錯了？這一問題的答案正在一點點地被人們接近。一篇由波士頓兒童醫院的研究人員和波士頓基地孤獨癥協會成員們發表在流行刊物《科學》上的論文揭示了5種新的與孤獨癥相關系的基因缺陷。根據疾病控制和預防中心記錄，已經發現有超過12種的遺傳缺陷和孤獨癥型譜紊亂有關，150個孩子中就會有一個被影響。但好消息是許多基因正開始適合病理樣本，波士頓的研究者們說。波士頓兒童醫院遺傳學領導人及論文的作者 Dr. Christopher Walsh 說：“當它看上去只是一份令人泄氣的基因發展列表時，我們卻從一個正在被顯現的共通路徑中受到鼓舞” 。

　　研究者們觀察了在中東和土耳其一些大家庭中發現的孤獨癥相關基因。堂兄弟姐妹間相互聯姻的大家庭最適合用來做隱性基因的研究。盡管這最近鑒定出的遺傳基因廣泛存在于人體的23對染色體中，但它們關系的功能：都主要體現在學習上。這些基因在大腦中活動在創造，鞏固和修改突觸路徑上——當我們學習新東西時，發生在物理和生物化學上的改變。這一部分暗示了在學習中孤獨癥可能基本上等于是分子的缺陷。

　　孤獨癥的癥狀典型地顯現在0-5歲之間——一個孩子正常得開始學習語言，社交技巧和其他新的能力的階段?？茖W家稱這種成長為“經驗依賴學習，”研究者們還認識到這和在腦電路中的巨大變化有關。至少有300個遺傳基因開開合合用于控制經驗依賴學習。這些基因中有任一的缺陷都有可能導致孤獨癥的癥狀?？赡軙袔装俜N孤獨癥的癥狀變化。從到目前為止研究人員們的發現來看，Walsh 說，“看上去幾乎沒有任何兩個相同的孤獨癥患兒——從所做的發現看，在幾乎每一個孩子中都會有不同的基因突變。”

　　一個令人振奮的發現：在中東家庭里發現的大多數遺傳缺陷并不在基因的商業部分里——鑒定大腦蛋白質的密碼。相反這些缺陷主要位于基因完全或部分開合的鄰近區域里。根據論文主要作者之一的馬薩諸塞州綜合醫院的Dr. Eric Morrow，建議一定的治療或藥物或許可以幫助這些基因活動規則劃。事實上， Morrow 猜想對患有孤獨癥的孩子加強說話和社交行為方面的早期干預計劃通過改變其受影響的基因表現或許會起到效果。（這一觀點已通過白鼠研究證實，實驗證明提供一個豐富刺激的環境可直接影響大腦中的基因表現。）

　　如同大多數的精神紊亂，孤獨癥在很大程度上是通過外部行為來定義的而不是完全的生物學上的理解。像對這種的遺傳研究，Morrow說, “提供了一個幻想的機會去定義病理學。” 為了開始給家庭一個解釋，他說，“是一件很大的事。”

　　在有關大范圍的孤獨癥潛在遺傳病因的陳述里，文章的最初譯文引用了馬薩諸塞州綜合醫院的 Dr. Eric Morrow的話，“看上去幾乎沒有任何兩個相同的孤獨癥患兒——在幾乎每一個孩子中都會有不同的基因突變。”盡管最初的引用內容報道正確，但提出的人卻弄錯了。那引言是由波士頓兒童醫院的 Dr. Christopher Walsh提出的。另外，研究者們指出陳述給出了令人誤解的印象就是所有患孤獨癥的孩子都被認識到有不一樣的遺傳缺陷。事實上，醫生只是對少數患有孤獨癥的孩子們做了檢查。引文已經被修正以反映重要的區別。

　　英文原文：

　　What exactly is going awry in the brains of people who have autism? The answer is very slowly coming into focus. A paper published in the current issue of Science by researchers at Children's Hospital Boston and members of the Boston-based Autism Consortium identifies five new autism-related gene defects. Already, more than a dozen genetic defects have been found to be associated with autism spectrum disorders, which affect about 1 in 150 children, according to the Centers for Disease Control and Prevention. But the good news, say the Boston researchers, is that many of the genes are beginning to fit into a pattern. "While it might seem discouraging that it's a growing list of genes, we can be encouraged that a common pathway is emerging," says Dr. Christopher Walsh, chief of genetics at Children's Hospital Boston and an author of the paper.

　　Researchers looked at autism-related genes found in large families in the Middle East and Turkey. Big families in which cousins sometimes marry cousins are ideal for studying recessive genes. Though the newly identified genes are located in far-flung regions on the 23 human chromosomes, they are related in function: most play a role in learning. These genes are active in creating, reinforcing or modifying synaptic pathways in the brain — physical and biochemical changes that occur when we learn something new. The implication of this work is that autism may fundamentally amount to molecular defects in learning.

　　Symptoms of autism typically emerge during the first five years of life — a period when a child normally picks up language, social skills and many other new abilities. Scientists call this kind of growth "experience-dependent learning," and researchers know that it is associated with enormous changes in brain circuitry. At least 300 genes switch on and off to regulate experience-dependent learning. Defects in any number of them could conceivably result in some symptoms of autism. There may be hundreds of varieties of autism. From what researchers have seen so far, says Walsh, "It looks like almost every child with autism is different from the next — where discoveries have been made, a different gene is mutated in almost every child."

　　One encouraging finding: most of the genetic defects identified in the Middle Eastern families were not in the business part of the gene — the part that codes for a critical brain protein. Instead the defects lay mainly in adjacent regions that turn the gene fully or partially on and off. This suggests that certain therapies or drugs could help normalize the activity of these genes, according to Dr. Eric Morrow of Massachusetts General Hospital, one of the lead authors of the paper. In fact, Morrow suspects that early intervention programs for children with autism involving intensive instruction in speech and social behavior may work by altering the expression of affected genes. (This idea is supported by research with mice, which has shown that providing a rich, stimulating environment directly affects gene expression in the brain.)

　　Autism, like most mental disorders, is largely defined by external behaviors rather than a clear biological understanding. Genetic studies like this one, observes Morrow, "offer a fantastic opportunity to define the pathology." To begin to give an explanation to families, he says, "is a big deal."

　　In a statement about the vast range of potential genetic causes of autism, the original version of this story quoted Dr. Eric Morrow of Massachusetts General Hospital as saying, "It looks like almost every child with autism is different from the next — a different gene is mutated in almost every child." Although the original quote was accurately reported, it was incorrectly attributed. The quote was stated by Dr. Christopher Walsh of Children's Hospital Boston. In addition, the researchers note that the statement gives the misleading impression that all children with autism are known to have different genetic defects. In fact, physicians have examined only a small percentage of children who have autism. The quote has been revised to reflect that important distinction.