【雙語閱讀】外因遺傳與壓力.

　　Science and Technology Epigenetics and stress Baby blues

　　A mother&aposs stress while she is pregnant can have a long-lasting fect on her children&aposs genes

　　RESEARCHERS have known for years that children whose mothers were chronically stressed during pregnancy—by famine, anxiety, the death of a relative or marital discord, for instance—show higher-than-normal rates of various psychological and behavioural disorders when they are adults. They have also known for a long time that those brought up in abusive environments often turn out to be abusive themselves. The second of these observations is usually put down to learning. The reason for the first has remained unclear. A study just published by Axel Meyer, Thomas Elbert and their colleagues at the University of Konstanz in Germany, however, points to a phenomenon called epigenetics as the likely answer. And if Drs Meyer and Elbert are right, it also suggests an alternative explanation for the inheritance of abusiveness.

　　Epigenetics is a type of gene regulation that can be passed from a cell to its daughters. The most common mechanism is methylation. This attaches methyl groups (a carbon atom and three hydrogens) to either adenine or cytosine, two of the four chemical bases that form the alphabet of DNA, depending on the gene involved. The consequence is to inactivate the gene being methylated.

　　In the case of stress, previous studies have suggested that methylation of the gene which encodes glucocorticoid receptors is important. Glucocorticoid receptors relay signals from stress hormones in the blood into cells. In particular, they do so in those regions of the brain that control behaviour. Newborns whose mothers suffered from depression while they were pregnant are known to have more highly methylated glucocorticoid-receptor genes than others. The same is true of children who were abused when young. In infants, the level of glucocorticoid-receptor methylation is correlated with the release, in response to stress, of higher-than-normal amounts of stress hormones. And in rats, such methylation makes young animals especially sensitive to stress, and also fearful of novelty.

　　What has been unclear until now, however, is how long such fects persist. Dr Meyer&aposs and Dr Elbert&aposs study, published in Translational Psychiatry, offers a clue.

　　Their team examined the methylation of the glucocorticoid-receptor gene in a group of children ranging in age from ten to 19 years, and in those children&aposs mothers. The researchers also used a psychological survey to try to determine which of the mothers had been physically or psychologically abused bore, during or after pregnancy. They found that women abused during pregnancy were significantly more likely than others to have a child with methylated glucocorticoid-receptor genes. By contrast, abuse bore or after pregnancy resulted in no such correlation. Nor was the mother&aposs own methylation affected by violence towards her. Taken together, these results suggest that glucocorticoid-receptor-gene methylation happens in the fetus in response to a mother&aposs stress, and persists into adolescence.

　　This has implications for those adolescents&apos long-term health. Dampened glucocorticoid-receptor-gene activity has been shown to increase the risk of obesity, of depression and of some autoimmune diseases. It also makes people more impulsive and aggressive—and therore, if male, more likely to abuse the pregnant mothers of their children, thus perpetuating the whole sorry cycle.

　　Why, in light of such negative fects, have humans evolved to be programmed this way while still in the womb? Part of the answer is probably that not all the negative consequences would have shown up at the time the mechanism was evolving. Obesity, for example, is rare in a state of nature. The other part is that some of the consequences probably have a positive fect. If a mother lives in an environment where fear-inducing experiences are common, say, giving her offspring a sensitivity to fear may be no bad thing.

　　What can be done with such knowledge is unclear. Drugs that demethylate DNA are under development, but are still some way from approval—and, in any case, interfering with epigenetics, which is a widespread mechanism of gene regulation, is a drastic approach. The research might, though, point to the period when intervening to stop abuse will have the greatest fect. Then again, such intervention is always desirable, for the sake of both mother and child.

　　【中文對(duì)照翻譯】

　　科技 外因遺傳與壓力 新生兒藍(lán)調(diào)曲

　　母親孕期壓力過大會(huì)對(duì)孩子的基因造成長期影響

　　研究人員多年前就發(fā)現(xiàn)，如果母親在懷孕期間長期遭受因饑餓，焦慮，親友死亡或婚姻不幸等引起的過大壓力，她們的孩子成年后出現(xiàn)各種心理疾病和行為問題的幾率會(huì)高于平均幾率。 研究人員也早知道，在受虐環(huán)境下成長起來的孩子長大后往往本身也有施虐傾向。人們通常把后面的這個(gè)發(fā)現(xiàn)歸咎于盲目效仿， 而頭一個(gè)發(fā)現(xiàn)的原因卻仍舊模糊不清。 然而，德國康士坦茨大學(xué)的Axel Meyer, Thomas Elbert以及他們的同儕們最近發(fā)表的研究報(bào)告指出，一種被稱為"外因遺傳"的現(xiàn)象很有可能就是這個(gè)問題的答案。 如果Meyer和Elbert博士的結(jié)論是正確的，那它也為施虐遺傳現(xiàn)象做出了另一個(gè)解釋。

　　外因遺傳是一種可以傳給下一代細(xì)胞的基因調(diào)控過程， 最常見的方式是通過甲基化作用來完成， 該作用可以讓甲基(由一個(gè)碳原子和三個(gè)氫原子組成)附著于腺嘌呤或胞嘧啶上。 腺嘌呤和胞嘧啶是DNA四大成分其中之二，而到底附著于哪一個(gè)則取決于具體的基因。 甲基化作用將使甲基化的基因失去活性。

　　以往的研究表明，當(dāng)母親壓力過大時(shí)，負(fù)責(zé)為糖皮質(zhì)激素受體編碼的基因的甲基化具有重要意義。 糖皮質(zhì)激素受體依靠血液中的壓力激素發(fā)出信號(hào)而進(jìn)入細(xì)胞。 尤其值得注意的是，這個(gè)過程在大腦中控制人體行為的區(qū)域進(jìn)行。 新生兒的母親若是在懷孕期間出現(xiàn)抑郁癥狀，他們糖皮質(zhì)激素受體基因的甲基化程度就會(huì)比其他新生兒更高。 幼時(shí)受虐的孩子在這一點(diǎn)上也有相同表現(xiàn)。 胎兒糖皮質(zhì)激素的甲基化程度與人體抑郁時(shí)分泌過多的壓力激素有關(guān)。 而老鼠試驗(yàn)表明，這樣的甲基化過程讓幼小動(dòng)物對(duì)壓力尤其敏感，對(duì)新鮮事物也感到恐懼。

　　然而，現(xiàn)在還沒弄清楚的是，這樣的效應(yīng)會(huì)持續(xù)多久。 Meyer博士和Elbert博士在《轉(zhuǎn)化精神病學(xué)》雜志中發(fā)表的研究報(bào)告給出了答案。

　　他們的研究小組對(duì)一組年齡從10歲到19歲不等的青少年以及他們母親體內(nèi)糖皮質(zhì)激素受體基因的甲基化程度進(jìn)行了測量， 還通過心理測試試著找出哪些母親在孕期中或者生產(chǎn)后曾遭到身體或者心理上的虐待。 研究發(fā)現(xiàn)，孕期中遭到虐待的母親生下糖皮質(zhì)激素受體基因被甲基化的幼兒的可能性要比其他母親高出得多。 相反，在孕前或是生產(chǎn)后遭到虐待的母親則不會(huì)生下這樣的幼兒， 而且她們本身基因的甲基化與否也跟是否遭到家庭暴力無關(guān)。 總體看來，這些結(jié)論表明胎兒糖皮質(zhì)激素受體基因的甲基化是由于母親壓力過大引起的，并且其影響將會(huì)持續(xù)到青春期。

　　這會(huì)影響青春期孩子的長期健康。 事實(shí)證明，糖皮質(zhì)激素受體基因不夠活躍會(huì)增加孩子患肥胖癥，抑郁癥以及某些免疫系統(tǒng)疾病的風(fēng)險(xiǎn)， 也會(huì)讓他們成年后個(gè)性更加沖動(dòng)，更加富有侵略性，因此，如果孩子是男性，他們更有可能施虐于懷著自己孩子的待產(chǎn)婦女，從而造成持續(xù)的惡性循環(huán)。

　　發(fā)現(xiàn)了這種消極效應(yīng)后，科學(xué)家們不禁問道，為何人類還在子宮內(nèi)的時(shí)候就被設(shè)立了這樣的一個(gè)進(jìn)化程序呢? 也許部分原因是，當(dāng)甲基化作用還在進(jìn)化的時(shí)候所有的消極影響不會(huì)當(dāng)即全部表現(xiàn)出來。 例如肥胖癥在極少數(shù)情況下是天生的。 還有一個(gè)原因是，部分消極影響也許會(huì)帶來積極效應(yīng)。 如果母親生活在一個(gè)很容易產(chǎn)生害怕心理的環(huán)境里，那么讓她的后代對(duì)害怕情緒敏感也許并不是壞事。

　　知道了這些真相對(duì)人們有什么意義尚不明確。 讓DNA反甲基化的藥物還在研發(fā)中，并且還未通過臨床證明。另外，外因遺傳是基因調(diào)控的常見手段。從任何角度來說，干預(yù)外因遺傳都是一種極端激進(jìn)的做法。 但這項(xiàng)研究也許會(huì)把科學(xué)家們引向另一個(gè)方向，那就是找出對(duì)基因調(diào)控進(jìn)行干涉從而阻止家庭暴力的最有效時(shí)期。 為了讓母親和孩子們都幸福，這樣的干涉乃眾望所歸。

　　Science and Technology Epigenetics and stress Baby blues

　　A mother&aposs stress while she is pregnant can have a long-lasting fect on her children&aposs genes

　　RESEARCHERS have known for years that children whose mothers were chronically stressed during pregnancy—by famine, anxiety, the death of a relative or marital discord, for instance—show higher-than-normal rates of various psychological and behavioural disorders when they are adults. They have also known for a long time that those brought up in abusive environments often turn out to be abusive themselves. The second of these observations is usually put down to learning. The reason for the first has remained unclear. A study just published by Axel Meyer, Thomas Elbert and their colleagues at the University of Konstanz in Germany, however, points to a phenomenon called epigenetics as the likely answer. And if Drs Meyer and Elbert are right, it also suggests an alternative explanation for the inheritance of abusiveness.

　　Epigenetics is a type of gene regulation that can be passed from a cell to its daughters. The most common mechanism is methylation. This attaches methyl groups (a carbon atom and three hydrogens) to either adenine or cytosine, two of the four chemical bases that form the alphabet of DNA, depending on the gene involved. The consequence is to inactivate the gene being methylated.

　　In the case of stress, previous studies have suggested that methylation of the gene which encodes glucocorticoid receptors is important. Glucocorticoid receptors relay signals from stress hormones in the blood into cells. In particular, they do so in those regions of the brain that control behaviour. Newborns whose mothers suffered from depression while they were pregnant are known to have more highly methylated glucocorticoid-receptor genes than others. The same is true of children who were abused when young. In infants, the level of glucocorticoid-receptor methylation is correlated with the release, in response to stress, of higher-than-normal amounts of stress hormones. And in rats, such methylation makes young animals especially sensitive to stress, and also fearful of novelty.

　　What has been unclear until now, however, is how long such fects persist. Dr Meyer&aposs and Dr Elbert&aposs study, published in Translational Psychiatry, offers a clue.

　　Their team examined the methylation of the glucocorticoid-receptor gene in a group of children ranging in age from ten to 19 years, and in those children&aposs mothers. The researchers also used a psychological survey to try to determine which of the mothers had been physically or psychologically abused bore, during or after pregnancy. They found that women abused during pregnancy were significantly more likely than others to have a child with methylated glucocorticoid-receptor genes. By contrast, abuse bore or after pregnancy resulted in no such correlation. Nor was the mother&aposs own methylation affected by violence towards her. Taken together, these results suggest that glucocorticoid-receptor-gene methylation happens in the fetus in response to a mother&aposs stress, and persists into adolescence.

　　This has implications for those adolescents&apos long-term health. Dampened glucocorticoid-receptor-gene activity has been shown to increase the risk of obesity, of depression and of some autoimmune diseases. It also makes people more impulsive and aggressive—and therore, if male, more likely to abuse the pregnant mothers of their children, thus perpetuating the whole sorry cycle.

　　Why, in light of such negative fects, have humans evolved to be programmed this way while still in the womb? Part of the answer is probably that not all the negative consequences would have shown up at the time the mechanism was evolving. Obesity, for example, is rare in a state of nature. The other part is that some of the consequences probably have a positive fect. If a mother lives in an environment where fear-inducing experiences are common, say, giving her offspring a sensitivity to fear may be no bad thing.

　　What can be done with such knowledge is unclear. Drugs that demethylate DNA are under development, but are still some way from approval—and, in any case, interfering with epigenetics, which is a widespread mechanism of gene regulation, is a drastic approach. The research might, though, point to the period when intervening to stop abuse will have the greatest fect. Then again, such intervention is always desirable, for the sake of both mother and child.

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