Stress and Epigenetics II — Early Life Experiences and Methylation

It’s too early to draw lasting conclusions about this stuff, but there’s interesting work going on in the epigenetics of stress.

A few weeks ago, I wrote a post on how stressing out mice during a particular window of time during pregnancy seemed to leave lasting epigenetic effects on descendants. I also mentioned a recent study by the University of British Columbia’s Michael Kobor and his colleagues at UBC and the University of Wisconsin School of Medicine that also hints at some critical windows of epigenetic sensitivity — but in humans. It’s that study I’m writing about now, and it points toward some great areas for follow-up research. (See the bottom of this post for the full reference.)

Most interestingly to me, it suggests that moms under stress leave epigenetic traces on infants of both genders that last at least until they’re 15 years old. What’s more, girls in the study — but not boys — appear to carry epigenetic changes at age 15 that may have originated from going through preschool age with a stressed dad.

I asked Michael Kobor about that last one — the paper mentions that there’s an association between paternal care of preschool girls and adolescent behavior. Is that really such a well-known phenomenon? “I’m a biochemist and geneticist by training, but when discussing this with our co-authors — who’re experts in the field — they were so positively surprised because it fit so well,” says Kobor. “It’s really quite well established in that domain, so they really took that as a confirmation that this approach works,” he says.

But here come the caveats. It’s a very preliminary study in a very new field. And it’s a fairly small sample size, with 109 kids whose parents took part in the Wisconsin Study of Families and Work. “Ideally, we would have liked to do this in a longitudinal fashion, with DNA that was collected at preschool, then again when they’re 15 or 16,” Kobor says.

Also, the epigenetic marks we’re talking about are a collection of methylated CpG sites significantly associated with growing up around either stressed moms or dads — 139 CpG sites in the case of stressed moms and 39 CpG sites in the case of dads. None of the tested CpG sites associated with specific genes showed epigenetic changes significantly correlated to parental stress, so it’s hard to know what the affected CpGs actually do. “As far as the specific genes go, it’s a bit of hand-waving,” Kobor says. “The reviewers  asked us to look at the genes that people have been focusing on immensely in the last couple years in these kinds of studies — the glucocorticoid receptors, BDNF, and those kinds of genes — we didn’t see any changes in those.”

It’s also hard to know if the buccal cells gathered by cheek-swabbing show the same epigenetic marks as neurons would — neuronal epigenetic changes are probably more important to behavior. And brain samples may be just slightly out of the question. “I’m not sure any parent would agree with that approach,” Kobor chuckles.

(Still, there’s a distant possibility that olfactory neurons gathered by nasal swabs might be more reflective of what’s going on in the human brain’s nerve cells — and Kobor says he’s actually talked to a few people about that approach. He also mentions the possibility that peripheral blood could tell researchers a bit about neuronal epigenetics. “Very few people have looked in the same individual at the correlation between brain methylation and, say, buccal cell methylation,” he says. Previous studies of rat epigenetics and mothering behavior used actual brain tissue, of course. “It would’ve been lovely if they’d gotten some buccal swabs too,” he adds.)

Next time, he and his colleagues plan to get a better look at the CpGs associated with glucocorticoid receptors — this study’s array could only test a couple of them. Their newest work uses an array that features more, along with a larger collection of relevant genes’ CpGs. “Now we’re asking the question, ‘Given that there are differences, are there any epigenetic marks correlated with behavior?’”

The newest research is also a longitudinal cohort, so Kobor and the rest of the team will know a lot more about the environment during pregnancy, and they might be able to associate that window of time with epigenetic marks too. “We have an entire suite of similar studies, both locally and with collaborators in the United States that probably look at the early life environment on epigenetics,” Kobor says.

He hopes to have a draft of the next one ready before the end of the year. And other groups are working on the stress connection all the time too. Maybe we’ll find a way to justify yoga to me yet!

(“Grads” photo by Flickr user campdarby reproduced here under a Creative Commons license.)

Essex MJ, Thomas Boyce W, Hertzman C, Lam LL, Armstrong JM, Neumann SM, & Kobor MS (2011). Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence. Child development PMID: 21883162