【双语阅读】外因遗传与压力.

　　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.

　　【中文对照翻译】

　　科技 外因遗传与压力 新生儿蓝调曲

　　母亲孕期压力过大会对孩子的基因造成长期影响

　　研究人员多年前就发现，如果母亲在怀孕期间长期遭受因饥饿，焦虑，亲友死亡或婚姻不幸等引起的过大压力，她们的孩子成年后出现各种心理疾病和行为问题的几率会高于平均几率。 研究人员也早知道，在受虐环境下成长起来的孩子长大后往往本身也有施虐倾向。人们通常把后面的这个发现归咎于盲目效仿， 而头一个发现的原因却仍旧模糊不清。 然而，德国康士坦茨大学的Axel Meyer, Thomas Elbert以及他们的同侪们最近发表的研究报告指出，一种被称为"外因遗传"的现象很有可能就是这个问题的答案。 如果Meyer和Elbert博士的结论是正确的，那它也为施虐遗传现象做出了另一个解释。

　　外因遗传是一种可以传给下一代细胞的基因调控过程， 最常见的方式是通过甲基化作用来完成， 该作用可以让甲基(由一个碳原子和三个氢原子组成)附着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，而到底附着于哪一个则取决于具体的基因。 甲基化作用将使甲基化的基因失去活性。

　　以往的研究表明，当母亲压力过大时，负责为糖皮质激素受体编码的基因的甲基化具有重要意义。 糖皮质激素受体依靠血液中的压力激素发出信号而进入细胞。 尤其值得注意的是，这个过程在大脑中控制人体行为的区域进行。 新生儿的母亲若是在怀孕期间出现抑郁症状，他们糖皮质激素受体基因的甲基化程度就会比其他新生儿更高。 幼时受虐的孩子在这一点上也有相同表现。 胎儿糖皮质激素的甲基化程度与人体抑郁时分泌过多的压力激素有关。 而老鼠试验表明，这样的甲基化过程让幼小动物对压力尤其敏感，对新鲜事物也感到恐惧。

　　然而，现在还没弄清楚的是，这样的效应会持续多久。 Meyer博士和Elbert博士在《转化精神病学》杂志中发表的研究报告给出了答案。

　　他们的研究小组对一组年龄从10岁到19岁不等的青少年以及他们母亲体内糖皮质激素受体基因的甲基化程度进行了测量， 还通过心理测试试着找出哪些母亲在孕期中或者生产后曾遭到身体或者心理上的虐待。 研究发现，孕期中遭到虐待的母亲生下糖皮质激素受体基因被甲基化的幼儿的可能性要比其他母亲高出得多。 相反，在孕前或是生产后遭到虐待的母亲则不会生下这样的幼儿， 而且她们本身基因的甲基化与否也跟是否遭到家庭暴力无关。 总体看来，这些结论表明胎儿糖皮质激素受体基因的甲基化是由于母亲压力过大引起的，并且其影响将会持续到青春期。

　　这会影响青春期孩子的长期健康。 事实证明，糖皮质激素受体基因不够活跃会增加孩子患肥胖症，抑郁症以及某些免疫系统疾病的风险， 也会让他们成年后个性更加冲动，更加富有侵略性，因此，如果孩子是男性，他们更有可能施虐于怀着自己孩子的待产妇女，从而造成持续的恶性循环。

　　发现了这种消极效应后，科学家们不禁问道，为何人类还在子宫内的时候就被设立了这样的一个进化程序呢? 也许部分原因是，当甲基化作用还在进化的时候所有的消极影响不会当即全部表现出来。 例如肥胖症在极少数情况下是天生的。 还有一个原因是，部分消极影响也许会带来积极效应。 如果母亲生活在一个很容易产生害怕心理的环境里，那么让她的后代对害怕情绪敏感也许并不是坏事。

　　知道了这些真相对人们有什么意义尚不明确。 让DNA反甲基化的药物还在研发中，并且还未通过临床证明。另外，外因遗传是基因调控的常见手段。从任何角度来说，干预外因遗传都是一种极端激进的做法。 但这项研究也许会把科学家们引向另一个方向，那就是找出对基因调控进行干涉从而阻止家庭暴力的最有效时期。 为了让母亲和孩子们都幸福，这样的干涉乃众望所归。

　　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.

上12下

共2页