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Early stress alters epigenome

Scientists have figured out how stress experienced early in life can cause long-lasting changes in physiology and behavior -- via epigenetics. Image: Max-Planck Institute of Psychiatry, MunichSpecifically, early stress appears to induce epigenetic changes in a specific regulatory region of the genome, affecting the expression of a hormone important in controlling mood and cognition into adulthood, according to a study published online today (November 8) in Nature Neuroscience. This is the fi

By | November 8, 2009

Scientists have figured out how stress experienced early in life can cause long-lasting changes in physiology and behavior -- via epigenetics.
Image: Max-Planck Institute of
Psychiatry, Munich
Specifically, early stress appears to induce epigenetic changes in a specific regulatory region of the genome, affecting the expression of a hormone important in controlling mood and cognition into adulthood, according to a study published online today (November 8) in Nature Neuroscience. This is the first study to depict a molecular mechanism by which "stress early in life can cause effects that remain later in life," said epigeneticist linkurl:Moshe Szyf;http://www.medicine.mcgill.ca/pharma/mszyflab/ of McGill University in Montreal. "This can explain a lot of things that happen to us as humans and our behavior later in life." Stress endured early in life can influence the quality of physical and mental health in adulthood, such as by causing hormonal alterations associated with mood and cognitive disorders. But until now, scientists did not understand the mechanism by which early life experiences can produce such long-lasting effects. According to a common hypothesis, the environment affects mental heath by causing alterations to the physical properties of the genome that influence gene expression -- the epigenome. Indeed, research suggests that DNA methylation, one of the most intensely studied forms of epigenetics, may explain why maternal care has a long-term influence on behavior and hormones in rats. To explore whether DNA methylation is behind the changes associated with stress experienced early in life, molecular biologists Chris Murgatroyd and Dietmar Spengler of the linkurl:Max Planck Institute of Psychiatry;http://www.mpg.de/english/institutesProjectsFacilities/instituteChoice/psychiatrie/index.html in Germany and colleagues examined the methylation patterns of mice that were separated from their mothers for three hours a day for the first ten days of their lives. Specifically, the researchers looked for differences in the gene that encodes arginine vasopressin (AVP), a hormone associated with mood and cognitive behaviors. The AVP receptor is also a promising therapeutic target for stress-related disorders. From 6 weeks of age all the way up to 1 year, mice that experienced early stress -- and showed the predicted behavioral and hormonal differences -- also displayed significantly lower levels of methylation in the regulatory region of the Avp gene in the brain. This hypomethylation was specific to a subset of neurons in the hypothalamic paraventricular nucleus -- a brain area involved in regulating hormones linked to stress. These mice also had higher levels of Avp mRNA, suggesting that lower methylation levels do indeed affect hormone levels. "Essentially the genome memorizes that [early life] stress," said Szyf, who was not involved in the study. "Stress changes methylation, and that stays the whole life." The researchers further determined that the decreases in methylation in stressed mice result from the inactivation of a protein known as MeCP2, which is involved in the initial recruitment of proteins that methylate the DNA. The concept that social states in early life can affect health in later life is "a completely revolutionary idea," Szyf said. This paper provides a "detailed" molecular mechanism by which this can occur, and "gives substance" to this theory. Understanding the molecular details underlying this phenomenon is essential to developing potential therapies for mental disorders that stem from early adverse experiences, Murgatroyd added. "This has given us new insight in how to possibly develop drugs for [these illnesses]." Treatments for reversing the effects of early life stress should begin as early as possible, Spengler said. Reversing the inactivation of MeCP2 might be possible, but "once [methylation] is laid down, you cannot erase [it]," he said. "This is a mark that is very stable." Treatments given later in life, then, must find ways to ameliorate the phenotype, such as by blocking AVP receptors in animals with higher AVP levels, he added.
**__Related stories:__***linkurl:Epigenetic suicide note;http://www.the-scientist.com/2009/08/1/18/1/
[August 2009]*linkurl:An epigenetic inheritance;http://www.the-scientist.com/blog/display/55342/
[19th January 2009]*linkurl:Epigenetics: Genome, Meet Your Environment;http://www.the-scientist.com/article/display/14798/
[5th July 2004]
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Comments

Avatar of: Kimberly Garland

Kimberly Garland

Posts: 1

November 9, 2009

Maybe we should re-think encouraging mothers to go back back to work so soon. Those baby mice had their basic needs met, what stressed them was the absence of their mother.
Avatar of: anonymous poster

anonymous poster

Posts: 9

November 9, 2009

As a previous poster has already said, if these findings can be applied to humans, there are serious implications for the way the Western world treats early childcare. The pressure to have both parents working, and contract out childcare, may create stress in the child which increases the risk of mental health problems - which seem to be on the increase. Maybe rising levels of obesity (as one example) can also be a result of these epigenetic changes. Could this be whatt Westernisation exports to other societies (such as Japan), that have a markedly different range of illnesses from what they had in the recent past?\n\nAll very interesting - maybe we can't undo the damage that has been done to individuals, but maybe we can prevent it in the future.
Avatar of: anonymous poster

anonymous poster

Posts: 77

November 9, 2009

It seems more than a bit of over reach to associate multiple temporary maternal separations in young nursing mice and their long-term effects with the global and indiscriminate term "stress". It may well indeed relate to one kind of stress and give insight into the pathways and long term effects of that type. However, to suggest that all kinds of early stressors in humans are so efficacious and, by implication, mammals in general, is reckless, wrong and bound to unleash a torrent of unwarranted suggestions and demands for all kinds of prescriptions and proscriptions. Witness the vast differences between cultures and how they wean and train their young to produce what each culture values in their grown members - all involve systematic accommodations and deprivations (calculated stressors) to achieve their ends. Headline grabber, for sure, but responsible? Not so much.
Avatar of: anonymous poster

anonymous poster

Posts: 5

November 9, 2009

This is interesting if the effect ends up being real in people. I wonder to what age it lasts. Many people allow their 6 month old babies to cry themselves to sleep. This may help dictate an appropriate age to expect children to sleep through the night alone.\n\nAlso, knowing the effects of early stress could help treat foster children who may be suffering from their early stress both from bad parenting and from loss of their parents.
Avatar of: Hal Stone

Hal Stone

Posts: 2

November 9, 2009

This seems to provide proof that Nurture affects Nature. It may not be direct human proof but wisdom should say that something similar will occur with humans.
Avatar of: Iwona Grad

Iwona Grad

Posts: 13

November 10, 2009

"...This is the first study to depict a molecular mechanism by which "stress early in life can cause effects that remain later in life," said epigeneticist Moshe Szyf of McGill University in Montreal. "This can explain a lot of things that happen to us as humans and our behavior later in life."..."\n\nThough I don't really have time to read thoroughly the paper, it seems that THE DISCOVERY was already made by Weaver et al, Nat Neurosci. 2004 Aug;7(8):847-54.\nEpigenetic programming by maternal behavior.:\n"...Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus....Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible...."\n\nSo again, where is THE DISCOVERY?
Avatar of: anonymous poster

anonymous poster

Posts: 1

November 17, 2009

Someone commented that "Maybe we should re-think encouraging mothers to go back back to work so soon. Those baby mice had their basic needs met, what stressed them was the absence of their mother."\n\nThis is an unwarranted assumption on your part. The effects seen her could just as easily be due to the pups' inability to regulate body temperature in the absence of the mother (a known issue). What we do have here is an environmental condition that produced a lasting molecular change. The mechanisms that link the extended maternal separation to the molecular change still need to be documented.\n\nIt's also worth remembering that multiple, brief (10-15 min) separations from the dam have been documented to IMPROVE rats' resistance to stress throughout their lives (an effect that seems to be mediated by increased maternal licking as noted earlier).\n\nThis is a complicated business, so be vary careful about drawing specific public policy implications from the currently available data.

December 6, 2009

I work with pregnant, birthing and early postpartum women. I think these findings support what midwives and natural birth advocates offer women and newborns - low intervention, gentle, physiologically normal births.\nWe've known what a difference birth outcomes can have on women and babies. Now if only ACOG, insurance companies, and hospital policy makers would just start following, supporting and practicing evidence based OBGYN care, lower their intervention rates and boost solid mother-infant attachment, we may be able to prevent a lot of these early stressors that cause lifelong mental health issues.

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