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创伤后遗症会传给后代子孙吗?

更新时间:2019/6/8 12:50:05 来源:纽约时报中文网 作者:佚名

Can the legacy of trauma be passed down the generations?
创伤后遗症会传给后代子孙吗?

In 1864, nearing the end of the US Civil War, conditions in the Confederate prisoner of war camps were at their worst. There was such overcrowding in some camps that the prisoners, Union Army soldiers from the north, each had the square footage of a grave. Prisoner death rates soared.

1864年,美国内战已近尾声,南方军战俘营的条件极其恶劣,有些地方人满为患,以至于战俘和北方军士兵,每个人都有一块一平方英尺的墓地,战俘死亡率飙升。

For those who survived, the harrowing experiences marked many of them for life. They returned to society with impaired health, worse job prospects and shorter life expectancy. But the impact of these hardships did not stop with those who experienced it. It also had an effect on the prisoners’ children and grandchildren, which appeared to be passed down the male line of families.

对于幸存者来说,这些惨痛的经历影响了他们当中许多人的一生。当他们重返社会时,身体垮了,工作比别人难找,去世得也早。但这些苦难造成的影响并没有随着亲历者的逝去而停止,那些战俘的子孙也受到影响,而且似乎是传男不传女。

While their sons and grandsons had not suffered the hardships of the PoW camps – and if anything were well provided for through their childhoods – they suffered higher rates of mortality than the wider population. It appeared the PoWs had passed on some element of their trauma to their offspring.

虽然他们的子孙并没有亲历战俘营的苦难,但即便童年衣食无虞,死亡率还是比其他人高。战俘似乎是把自己的一些创伤因素传给了后代。

But unlike most inherited conditions, this was not caused by mutations to the genetic code itself. Instead, the researchers were investigating a much more obscure type of inheritance: how events in someone’s lifetime can change the way their DNA is expressed, and how that change can be passed on to the next generation.

但与大多数遗传不同的是,这并非是由遗传编码本身的突变所引起。研究人员正在研究一种更隐秘的遗传:人这一生中发生的事情如何改变了DNA的表达方式,以及这种改变是如何传给下一代的。

This is the process of epigenetics, where the readability, or expression, of genes is modified without changing the DNA code itself. Tiny chemical tags are added to or removed from our DNA in response to changes in the environment in which we are living. These tags turn genes on or off, offering a way of adapting to changing conditions without inflicting a more permanent shift in our genomes.

这个过程名为表观遗传,即在DNA编码本身不变的情况下,基因的可读性或表达发生变化。当生活环境发生改变,我们的DNA会做出细微的化学反应。这些反应将基因打开或者关闭,提供了一种方法,能让我们适应不断变化的环境,而不会对基因组造成更为持久的改变。

But if these epigenetic changes acquired during life can indeed also be passed on to later generations, the implications would be huge. Your experiences during your lifetime – particularly traumatic ones – would have a very real impact on your family for generations to come. There are a growing number of studies that support the idea that the effects of trauma can reverberate down the generations through epigenetics.

如果人一生中所出现的表观遗传变化确实会遗传给后代,那么其影响将是巨大的。你一生的经历——尤其是创伤性经历——将切实影响家里的若干代人。越来越多的研究都认为,创伤后遗症可以通过表观遗传影响几代人。

For the PoWs in the Confederate camps, these epigenetic changes were a result of the extreme overcrowding, poor sanitation and malnutrition. The men had to survive on small rations of corn, and many died from diarrhoea and scurvy.

对于南方战俘营的俘虏来说,这些表观遗传变化是由人满为患、卫生条件恶劣和营养不良造成的。他们的口粮只有一点点玉米,许多人死于腹泻和坏血病。

“There is this period of intense starvation,” says study author Dora Costa, an economist at the University of California, Los Angeles. “The men were reduced to walking skeletons.”

“饥饿问题严重,”加州大学洛杉矶分校的经济学家,也是该研究报告的作者科斯塔(Dora Costa)说。“人们饿得只剩皮包骨头。”

Costa and her colleagues studied the health records of nearly 4,600 children whose fathers had been PoWs, comparing them to just over 15,300 children of veterans of the war who had not been captured.

科斯塔和同事们研究了近4,600名战俘子女的健康记录,并与15,300多名没有被俘的退伍军人后代进行了对比。

The sons of PoWs had an 11% higher mortality rate than the sons of non-PoW veterans. Other factors such as the father’s socioeconomic status and the son’s job and marital status couldn’t account for the higher mortality rate, the researchers found.

战俘儿子的死亡率比非战俘的儿子高出11%。研究人员发现,父亲的社会经济地位、儿子的工作和婚姻状况等其他因素,并不能解释死亡率为何会更高。

This excess mortality was mainly due to higher rates of cerebral haemorrhage. The sons of PoW veterans were also slightly more likely to die from cancer. But the daughters of former PoWs appeared to be immune to these effects.

高死亡率主要是因为脑溢血的比例较高。被俘军人的儿子死于癌症的概率也略高,但女儿似乎不受影响。

This unusual sex-linked pattern was one of the reasons that made Costa suspect that these health differences were caused by epigenetic changes. But first Costa and her team had to rule out that it was a genetic effect.

这种不寻常的性别关联令科斯塔怀疑,表观遗传变化是导致这些健康差异的原因之一。但首先,她和研究团队必须排除这是一种遗传效应。

“What could have happened is that a genetic trait which enabled the father to survive the camp, a tendency toward obesity for example, was then bad during normal times,” says Costa. “However, if you look within families, there are only effects among sons born after but not before the war.”

科斯塔说:“有一种可能是,父亲得以在战俘营中存活的某种基因特征在正常年代是不好的,例如肥胖倾向。观察他的家庭你会发现,只有战后出生的儿子会受到影响,战前的不会。”

If it were a genetic trait then children born before and after the war would be equally likely to show the reduced life expectancy. With a genetic cause ruled out, the most plausible explanation left was an epigenetic effect.

如果这是一种基因特征,那么战前和战后出生的孩子预期寿命都该缩短。排除掉基因原因,最可能的解释就是表观遗传效应。

“The hypothesis is that there’s an epigenetic effect on the Y chromosome,” says Costa. This effect is consistent with studies in remote Swedish villages, where shortages in food supply had a generational effect down the male line, but not the female line.

“我们假设Y染色体存在一种表观遗传效应,”科斯塔说。这种效应与在瑞典一些偏远村庄所做的研究一致,在那里,食物短缺对男性后代产生了影响,对女性后代则不然。

But what if this increased risk of death was due to a legacy of the father’s trauma that had nothing to do with DNA? What if traumatised fathers were more likely to abuse their children, leading to long-term health consequences, and sons bore the brunt of it more than daughters?

但如果死亡风险增加是父亲创伤遗留的其他因素所致,与DNA无关呢?如果是因为父亲受过创伤后更有可能虐待孩子,给孩子健康造成长期影响,而且儿子比女儿受的伤害更大呢?

Once again, comparing the health of children within families helped rule this out. Children born to men before they became PoWs didn’t have a spike in mortality. But the sons of the same men after their PoW camp experience did.

再来比比一家中孩子们的健康状况,这种可能性就被排除了。男性被俘之前出生的孩子死亡率不会激增,但被俘之后出生的孩子死亡率却大大增加。

“It’s a case of ruling out the other possible options,” says Costa. “A lot of it is proof by elimination and what is the most consistent explanation.”

“这是在排除其他可能性,”科斯塔说。“很多都是通过排除法来证明,剩下一个最合理的解释。”

Many of the times when trauma is thought to have echoed down the generations via epigenetics in humans are linked to the darkest moments in history. Wars, famines and genocides are all thought to have left an epigenetic mark on the descendants of those who suffered them.

认为创伤会通过表观遗传代代相传的年代,许多都是历史上最黑暗的时期,战争、饥荒和种族灭绝都被认为在亲历者的后代身上留下了表观遗传的印记。

Some studies have proved more controversial than others. A 2015 study found that the children of the survivors of the Holocaust had epigenetic changes to a gene that was linked to their levels of cortisol, a hormone involved in the stress response.

有些研究颇具争议。2015年的一项研究发现,在二战犹太人大屠杀中幸存者的子女身上,一个与皮质醇水平有关的基因发生了表观遗传变化,皮质醇是一种应激反应激素。

“The idea of a signal, an epigenetic finding that is in offspring of trauma survivors can mean a lot of things,” says Rachel Yehuda, director of the Traumatic Stress Studies Division at the Mount Sinai School of Medicine and an author of the study. “It’s exciting that it’s there.”

“有种观点认为,在创伤幸存者后代身上有某种信号,能发现某种表观遗传,这一观点意义重大,”西奈山医学院创伤压力研究部主任,也是该项研究作者之一的耶胡达(Rachel Yehuda)说。“这很令人兴奋。”

The study was small, assessing just 32 Holocaust survivors and a total of 22 of their children, with a small control group. Researchers have criticised the conclusions of the study. Without looking at several generations and searching more widely in the genome, we can’t be sure it is really epigenetic inheritance.

这项研究的规模很小,只有32名大屠杀幸存者及他们的22名子女,实验的对照组也很小。研究人员对这项研究的结论提出了批评。如果没有对若干代人的观察,没有在基因组中进行更广泛的研究,就不能确定这是不是表观遗传。

Yehuda acknowledges that the paper was blown out of proportion in some reports, and larger studies assessing several generations would be needed draw firm conclusions.

耶胡达承认,这篇论文在一些报告中被夸大了,要想得出确定的结论,需要对数代人进行更大规模的评估。

“It was one single small study, a cross-section of adults many, many years after parental trauma. The fact we got a hint was big news,” says Yehuda. “Now the question is, how do you put meat on the bones? How do you really understand the mechanism of what is happening?”

她说:“这是一项单独的小规模研究,只选取了一部分父母在很多年前受过创伤的成年人。我们得到的启示是个大新闻,现在的问题是,如何解释这个问题?如何真正理解背后的原理?”

Controlled experiments in mice have allowed researchers to hone in on this question. A 2013 study found that there was an intergenerational effect of trauma associated with scent. The researchers blew acetophenone – which has the scent of cherry blossom – through the cages of adult male mice, zapping their foot with an electric current at the same time. Over several repetitions, the mice associated the smell of cherry blossom with pain.

通过在小鼠身上进行对照实验,研究人员能够深入研究这个问题。2013年的一项研究发现,与气味有关的创伤存在代际影响。研究人员对成年雄鼠的笼子吹有樱花气味的乙酰苯,同时电击雄鼠的脚。 数次过后,雄鼠将樱花的气味与疼痛联系在了一起。

Shortly afterwards, these males bred with female mice. When their pups smelled the scent of cherry blossom, they became more jumpy and nervous than pups whose fathers hadn’t been conditioned to fear it. To rule out that the pups were somehow learning about the smell from their parents, they were raised by unrelated mice who had never smelt cherry blossom.

不久,这些雄鼠与雌鼠交配。它们生下的幼鼠闻到樱花味时,会比那些父亲没有对樱花味培养出恐惧感的幼鼠更加神经质、更加紧张。为了排除幼鼠会从父母那里知道这种气味的可能性,它们是由从未闻过樱花气味、毫不相关的小鼠抚养长大的。

The grandpups of the traumatised males also showed heightened sensitivity to the scent. Neither of the generations showed a greater sensitivity to smells other than cherry blossom, indicating that the inheritance was specific to that scent.

受创伤雄鼠的孙辈也对樱花味特别敏感。这两代小鼠都没有对其他气味表现出更强的敏感度,表明遗传只针对樱花味。

This sensitivity to cherry blossom scent was linked back to epigenetic modifications in their sperm DNA. Chemical markers on their DNA were found on a gene encoding a smell receptor, expressed in the olfactory bulb between the nose and the brain, which is involved in sensing the cherry blossom scent. When the team dissected the pups’ brains they also found there was a greater number of the neurons that detect the cherry blossom scent, compared with control mice.

这种对樱花气味的敏感度与雄鼠精子DNA中的表观遗传改变有关。研究发现,幼鼠DNA中的一个基因发生了化学变化,这个基因可以接收气味,基因表达于鼻子和大脑之间能够感知樱花味的嗅球中。研究小组将幼鼠的大脑解剖后发现,与对照组相比,它们探测樱花气味的神经元数量更多。

The second and third generation appeared to have not a fear of the scent itself, but a heightened sensitivity to it. The finding brings to light an often-missed subtlety of epigenetic inheritance – that the next generation doesn’t always show exactly the same trait that their parents developed. It is not that fear is being passed down the generations – it is that fear of a scent in one generation leads to sensitivity to the same scent in the next.

雄鼠的子辈和孙辈似乎并不害怕气味本身,只是对它更为敏感。这一发现揭示出表观遗传经常被忽略的一个细节:子女并不总是表现出与父母完全相同的特征。代代相传的并非恐惧,一代人对某种气味的恐惧会导致下一代对这种气味敏感。

“So this is not ‘apples for apples’,” says Brian Dias, author of the study and a researcher at Emory University and the Yerkes National Primate Research Center in the US. Even the term “inheritance” should be qualified here, he adds. “The word inheritance suggests it has to be a faithful representation of a trait that’s passed down.”

“所以两者并不相同,”该研究的作者,也是美国埃默里大学和美国耶基斯国家灵长类动物研究中心的研究员迪亚斯(Brian Dias)如是说。他还表示,“遗传”一词在这里也值得推敲,“遗传意味着将沿袭的特质原原本本地表现出来。”

The consequences of passing down the effects of trauma are huge, even if they are subtly altered between generations. It would change the way we view how our lives in the context of our parents’ experience, influencing our physiology and even our mental health.

哪怕创伤的影响在代际间发生了微妙的变化,传递它的影响也十分重大。父母的经历会改变我们对生活的看法,影响我们的生理甚至心理健康。

And knowing that the consequences of our own actions and experiences now could affect the lives of our children – even long before they might be conceived – could put a very different spin on how we choose to live.

我们自己的行为和经历可能会影响子女的生活——甚至是怀上他们之前很久的行为经历,知道这一点,可能会大大改变我们选择如何生活。

Despite picking up these echoes of trauma down the generations, there is a big stumbling block with research into epigenetic inheritance: no one is sure how it happens. Some scientists think that it is actually a very rare event.

尽管已经发现创伤会波及几代人,但表观遗传的研究还存在一个巨大障碍:没人知道它是如何发生的。一些科学家认为,表观遗传其实非常罕见。

One of the reasons that it may not be widespread is that the vast majority of one type of epigenetic mark on the DNA – the addition of a clump of chemicals known as methylation – is wiped clean at the very start of life and the process of adding these chemical groups to the DNA begins almost from scratch.

不常见的原因之一在于,DNA中有一种表观遗传印记,其绝大部分在生命形成之初就被清除得一干二净,这指的是在DNA中添加一团名为甲基化的化学物质,将它们添加到DNA的过程几乎是从零开始。

“As soon as the sperm enters the egg in a mammal, there’s a rapid loss of DNA methylation from the paternal set of chromosomes,” says Anne Ferguson-Smith, a researcher studying epigenetics at the University of Cambridge.  “That’s the reason why transgenerational epigenetic inheritance is such a surprise.

“一旦哺乳动物的精子进入卵细胞,父亲染色体中DNA的甲基化就会迅速消失,”剑桥大学表观遗传学的研究者弗格森-史密斯(Anne Ferguson-Smith)说。“所以出现跨代的表观遗传很令人意外。”

“It’s very hard to imagine how you could have epigenetic inheritance when there’s a process of removal of all the epigenetic marks and putting on new ones in the next generation.”

“如果所有的表观遗传印记都会被清除,由下一代重新添加,很难想象为何还会出现表观遗传。”

There are, however, parts of the genome that are not wiped clean. A process called genomic imprinting protects the methylation at specific points of the genome. But these sites are not the ones where the epigenetic changes relevant to trauma are found.

然而,基因组的某些部分并没有被完全抹去。一个名为基因组印迹的过程保护了基因组某些部位的甲基化。但与跟创伤有关的表观遗传所发生变化的地方并不一致。

A recent study by Ferguson-Smith’s group suggests epigenetic inheritance is probably very rare in mice.

弗格森-史密斯团队最近的一项研究表明,表观遗传在小鼠中可能非常罕见。

But other researchers are convinced that they have found the hallmarks of epigenetic inheritance for several traits – in humans as well as animals. What’s more, they think they’ve found a mechanism for how it works. This time it could be molecules similar to DNA – known as RNA – that are altering how genes function.

但其他研究人员相信,他们已经发现了若干特性的表观遗传特征,有人类的也有动物身上的。此外,他们还自认发现了表观遗传的运作机制,认为可能是由于一种类似DNA的分子改变了基因的运作方式,这种分子名为RNA。

A recent paper has revealed strong evidence that RNA may play a role in how the effects of trauma can be inherited. Researchers examined how trauma early in life could be passed on by taking mouse pups away from their mothers right after birth.

最近一篇论文拿出了强有力的证据,表明在创伤如何影响遗传的方面,RNA可能发挥了作用。研究人员在幼鼠出生后立即将它们从母亲身边带走,借此观察早前受到的创伤是如何传递的。

“Our model is quite unique,” says Isabelle Mansuy of the University of Zürich and ETH Zürich, who led the research. “It’s to mimic dislocated families, or the abuse, neglect and emotional damage that you sometimes see in people.”

这项研究的带头人芒叙(Isabelle Mansuy)同时在苏黎世大学和苏黎世联邦理工学院任职,她说:“我们的模式非常独特,有些人会与家人分离,或是被虐待忽视,情感受到伤害,我们模拟了这些情况。”

The symptoms these pups showed as they grew up also mimicked the symptoms seen in children who have experienced early trauma. The mice showed signs of increased risk-taking and higher calorie intake, both seen in child trauma survivors. When the males grew up, they had pups that showed similar traits – overeating, risk taking and higher levels of antisocial behaviour.

这些幼鼠在成长过程中表现出的症状,跟早年受过创伤的儿童症状相类似。这些小鼠更容易冒险,会摄入更多热量,这在从创伤中幸存的儿童身上都能看到。当雄鼠成年后,它们的幼鼠也表现出类似特征——暴饮暴食、爱冒险以及更高程度的反社会行为。

The researchers extracted RNA molecules from the sperm of male mice who had been traumatised and injected these molecules into early the embryos of mice whose parents had not experienced this early-life trauma. The resulting pups, however, showed the typical altered behavioural patterns of a pup whose parents experienced trauma.

研究人员从受过创伤的雄鼠精子中提取出RNA分子,注射到父母早年没有经历过这种创伤的小鼠的早期胚胎中。这些幼鼠的行为模式也发生了特定改变,与父母经历过创伤的幼鼠变化一致。

They also found that different lengths of RNA molecules were linked to different behavioural patterns: longer RNAs corresponded to greater food intake, changed the body’s response to insulin and greater risk-taking. Smaller RNA molecules were linked to showing signs of despair.

他们还发现,不同长度的RNA分子与不同的行为模式相关:RNA较长则食物摄入量更大,改变了身体对胰岛素的反应,并且更爱冒险。RNA分子较小的则会表现出绝望。

“It’s the first time we’ve seen this link in a causal way,” says Mansuy.

“这是我们第一次看到这种联系的因果关系,”芒叙说。

How these RNA molecules alter the behaviour of multiple generations is not yet known. Mansuy is now running experiments in humans to see if similar processes are at work in humans. Initial experiments by other researchers have shown that this does seem to be the case in men.

这些RNA分子是如何改变了几代人的行为目前尚不清楚。芒叙正在人类身上试验,看看类似情况是否也会出现。其他研究者的初步试验表明,男性似乎确实如此。

This research – as well as many of the mice studies – focus on sperm and epigenetic inheritance down the male line. This isn’t because scientists think it only happens in males. It’s just a lot harder to study eggs than it is to study sperm.

这项研究,以及许多在小鼠身上进行的研究都将重心放在精子和雄性后代的表观遗传上。并不是因为科学家认为这种情况只发生在男性身上,而是因为研究卵子要比研究精子困难得多。

But efforts to decipher epigenetic inheritance down the female line is the next step.

但接下来的工作,就是破译雌性后代的表观遗传。

“We had to start from somewhere,” says Mansuy. “But we are looking to have a model of trauma that shows how inheritance occurs via both females and males.”

“我们得先从一个地方开始研究,”芒叙说。“但我们希望建立一个创伤模型,将遗传在女性和男性身上的发生机制都能解释清楚。”

There are other known kinds of epigenetic mechanisms that are relatively little studied. One of them is called histone modification, where the proteins that act as a scaffold for DNA are chemically tagged. Now research is starting to suggest that histones could also be involved in epigenetic inheritance through the generations in mammals.

还有一些已知的表观遗传机制,但相对而言研究得不多。其中一个是组蛋白修饰,即作为DNA支架的蛋白质被做了化学标记。研究渐渐表明,组蛋白也可能参与了哺乳动物代际间的表观遗传。

“I suspect the answer is that all of these mechanisms could interact to give us the phenomenon that is intergenerational inheritance of acquired traits,” says Dias.

“我认为可能所有机制都在相互作用,共同形成了后天特征的代际遗传现象,”迪亚斯说。

The science of epigenetic inheritance of the effects of trauma is young, which means it is still generating heated debate. For Yehuda, who did pioneering work on Post-Traumatic Stress Disorder in the 1990s, this comes with a sense of déjà vu.

受创伤影响的表观遗传科学还很年轻,意味着仍在引发激烈的讨论。耶胡达对这种感觉似曾相识——上世纪90年代,她在创伤后应激障碍(Post-Traumatic Stress Disorder,简称PTSD)方面进行了开创性的研究。

“Where we are with epigenetics today feels like how it was when we first started doing research into PTSD,” she says.  “It was a controversial diagnosis. Not everyone believed there could be long term effect of trauma.”

“我们现在对表观遗传学的研究,感觉就像当年刚开始研究PTSD时一样,”她说。“这是一个有争议的结论,并不是每个人都认为创伤会造成长期影响。”

Nearly 30 years later, PTSD is a medically accepted condition that explains why the legacy of trauma can span decades in a person’s lifetime.

近30年后,PTSD成了被医学承认的疾病,它解释了为什么创伤后遗症会伴随人几十年。

But if trauma is shown to be passed down the generations in humans in the same way as it appears to be in mice, we shouldn’t feel a sense of inevitability about this inheritance, says Dias.

但是迪亚斯说,就算研究表明创伤会像在小鼠身上一样在人的身上代代相传,我们也无需认为创伤遗传就是不可避免的。

Using his cherry blossom experiments in mice, he tested what would happen if males that feared the scent were later desensitised to the smell. The mice were repeatedly exposed to the scent without receiving a foot shock.

还是这个在小鼠身上做的樱花实验,迪亚斯测试了如果害怕樱花味的雄鼠后来对气味脱敏会怎样。实验反复让小鼠闻到樱花味,但不再电击脚部。

“The mouse hasn’t forgotten, but a new association is being formed now this odour is no longer paired with the foot shock,” says Dias.

“小鼠并没有忘记,但正在形成新的联系,樱花味不再意味着脚被电击,”迪亚斯说。

When he looked at their sperm, they had lost their characteristic “fearful” epigenetic signature after the desensitisation process. The pups of these mice also no longer showed the heightened sensitivity to the scent. So, it if a mouse “unlearns” the association of a scent and pain, then the next generation may escape the effects.

迪亚斯观察小鼠的精子,发现脱敏过程后,精子不再有那种“感到害怕”的表观遗传特征。它们的幼鼠也不再表现出对樱花味的高度敏感。因此,如果一只小鼠“忘掉”某种气味和疼痛之间的联系,下一代可能就不再会受此影响。

It also suggests that if humans inherit trauma in similar ways, the effect on our DNA could be undone using techniques like cognitive behavioural therapy.

实验还表明,如果人类以类似的方式继承了创伤,DNA受到的影响可以通过认知行为疗法等手段来消除。

“There’s a malleability to the system,” says Dias. “The die is not cast. For the most part, we are not messed up as a human race, even though trauma abounds in our environment.”

“这个系统具有可塑性,”迪亚斯说。“并非不可改变。尽管我们周围创伤四伏,但人类在大多数情况下并没有被搞得一团糟。”

At least in some cases, Dias says, healing the effects of trauma in our lifetimes can put a stop to it echoing further down the generations.

迪亚斯说,至少在某些情况下,治愈我们的创伤可以阻止它去影响后几代人。

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