‘The mind . . . in itself can make a heaven of hell, a hell of heaven’

Remarkable article about how our social experience and the way we come to frame our lives influences gene-expression.

I would’ve bet my eyeteeth that we’d get a lot of noisy results that are inconsistent from one realm to another. And at the level of individual genes that’s kind of true—there is some noise there.” But the kinds of genes that get dialed up or down in response to social experience, he said, and the gene networks and gene-expression cascades that they set off, “are surprisingly consistent—from monkeys to people, from five-year-old kids to adults, from Vancouver teenagers to 60-year-olds living in Chicago.”

The principal pathway through which this works appears to be the immune system.

Normally, a healthy immune system works by deploying what amounts to a leashed attack dog. It detects a pathogen, then sends inflammatory and other responses to destroy the invader while also activating an anti-inflammatory response—the leash—to keep the inflammation in check. The lonely Chicagoans’ immune systems, however, suggested an attack dog off leash—even though they weren’t sick. Some 78 genes that normally work together to drive inflammation were busier than usual, as if these healthy people were fighting infection. Meanwhile, 131 genes that usually cooperate to control inflammation were underactive. The underactive genes also included key antiviral genes.

This opened a whole new avenue of insight. If social stress reliably created this gene-expression profile, it might explain a lot about why, for instance, the lonely HIV carriers in Cole’s earlier studies fell so much faster to the disease. [These mechanisms might also, on the flip side, go a long way towards explaining the placebo effect.]

The effects of these at times remarkably rapid shifts in gene-expression are not only physical, but also mental. A 2004 study examined 57 children “who were so badly abused that state social workers had removed them from their homes.”

Kaufman looked first to see whether the kids’ mental health tracked their SERT [“the so-called depression risk gene—the serotonin transporter gene”] variants. It did: The kids with the short variant suffered twice as many mental-health problems as those with the long variant. The double whammy of abuse plus short SERT seemed to be too much.

Then Kaufman laid both the kids’ depression scores and their SERT variants across the kids’ levels of “social support.” In this case, Kaufman narrowly defined social support as contact at least monthly with a trusted adult figure outside the home. Extraordinarily, for the kids who had it, this single, modest, closely defined social connection erased about 80 percent of the combined risk of the short SERT variant and the abuse. It came close to inoculating kids against both an established genetic vulnerability and horrid abuse.

I was stunned when I read this. Not because it doesn’t make sense (in many ways, it makes all too much sense), but because it opens up such a vista of both hope and sadness; so much misery about for want of a deeply trusted connection.

A later study concluded “[t]he main thing driving screwy immune responses appeared to be not poverty, but whether the child saw the social world as scary.” Not that poverty is irrelevant, of course, but it seems much of its negative effect comes from the social environment it tends to create. An environment where the world, and other people, are far more often viewed as threatening.

The message tentatively coming out of all of this is by no means straightforward. It could easily be construed as deterministic with our environment heavily shaping how we see the world and also, therefore, how we, and our bodies, react. On the other hand, our perceptions seem to be astonishingly important

To an extent that immunologists and psychologists rarely appreciate, we are architects of our own experience. Your subjective experience carries more power than your objective situation. If you feel like you’re alone even when you’re in a room filled with the people closest to you, you’re going to have problems. If you feel like you’re well supported even though there’s nobody else in sight; if you carry relationships in your head; if you come at the world with a sense that people care about you, that you’re valuable, that you’re okay; then your body is going to act as if you’re okay—even if you’re wrong about all that.”

In some ways this all seems a little Norman Vincent Pealish. Only superficially though, I think. Two things make it different. First, a recognition of the bootstrapping dilemma is inherent in the dominant gene-expression processes now known to be at work; if the world seems scary, and you feel alone in facing it, no amount of exhortations to think positively is likely to work. You’re more or less nobbled from day one. Secondly, the value of individual, trusting connections is made heartbreakingly clear. One, it seems, can sometimes be enough, no matter how appalling an individual’s circumstances otherwise.

 

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conrad
conrad
8 years ago

Most of this is a fair bit of hyperbole, and these sorts of articles are often written to exploit it (like this one). You basically start off with a really constrained example from some tiny creature with some tiny brain, and show how you get great environmental effects and find a few genetic correlates that differ. You go up the chain a bit, and finally get to humans, and then find some example of the worst of the worst thing you can think of. Ultra-serious child abuse in this case. You then find out that these kids get bad outcomes under any circumstances. Of course we’ve known this essentially forever, without having to mention the word gene, brain, or anything else (Romanian orphans come to mind as the older classic example), and we’ve also known that looking at these groups doesn’t tell us much about 99% of the rest of the population, since there’s no straight line between worst-of-worst->bad->normal->good.

Even accepting that these cases might tell us something about something, you might notice that you’ve gone from talking about genetics that is still especially poorly understood to complex phenomena so poorly understood and dispersed in terms of the consequences that the best we can do is get correlates with genes. But this really tells us nothing about how the genes map to complex behavior — In their human example, they even note that there are over 200 genes doing different stuff. I’ll point out here that all of these can potentially have different expressions at different time points and interact with each other. So you could have a 200+ way interaction just at one time point, let alone if you want to add time in. And these are just the ones they happened to find that correlate in a nice linear way — you can find this many significant correlations for many simpler functions, so I’m willing to bet as the technology gets better, they’ll find a plethora more. Let alone once they start looking for more complex relationships than is currently done.

So as far as I can tell, we haven’t learnt anything we didn’t know, except that there is some balance between nature/nurture, and that having fancy stories about genes probably helps you get your next grant. They should have given us a picture of brain development differences too. I’m happy to predict the differences before they do the study. They would be: large changes in the hippocampus (stress hormones affect its develpment), and lesser effects in other subcortical and frontal areas. Possibly minor stuff everywhere else for really bad cases. But that still tells us nothing about the function of genes, apart from the fact they have lots of functions and we really don’t know SFA about how they predict complex behavior.

conrad
conrad
8 years ago
Reply to  Ingolf Eide

It’s the next new area of public misunderstanding. The reality is that there were many super finds when looking for single genes, and so people expect greatness (you might like to call this the early low-hanging fruit). But the reality at the other end is that we can’t even define a lot of complex behaviors well. But if you add a genetics story or a brain story and call it neuro-genetics, suddenly everyone believes it, no matter how unfalsfiable it is and no matter how simplistic the models are that are finding what amounts to large numbers of simple correlations.

You then call for huge amounts of money to be spent on public screening etc. .

Here’s a good example from my area:

Here is the press release:

http://news.yale.edu/2013/06/12/yale-researchers-unravel-genetics-dyslexia-and-language-impairment

and you can read the reality from one of the people that has perhaps done the most work on genetics and language of anyone:

http://deevybee.blogspot.co.uk/2013/06/overhyped-genetic-findings-case-of.html

Paul Frijters
Paul Frijters
8 years ago
Reply to  Ingolf Eide

I sympathise with Conrad’s basic point that these gene-expression stories are often old wine in new caskets. What is ‘exciting’ is mainly the young crowd ignoring the old crowd whilst pushing a similar message, ie generational take-over in the journal game.

But I do think there are some real lessons in gene-expression research, the main one being that there is nurture in nature. One of the big points of the existence of epigenetic mechanisms is that it implies that identical twin studies do not necessarily identify the importance of genes, but may merely pick up common gene expression. In terms of research methodology and popular stories about genetics, that is a biggie because it undermines a lot of medical research and gene-based popular social science.

Paul Frijters
Paul Frijters
8 years ago
Reply to  Ingolf Eide

:-) I have a whole post all written on epigenetics and twin studies, simply don’t have the time now to finish it and put it up. Will get round to it when back from Europe.

Sancho
Sancho
8 years ago

All sounds a bit Lamarckist.

It would be silly to suggest that genetics are fully understood and we can just close the book on further theorising, but anything that suggests our genetic legacy can be altered by environment and behaviour should be viewed as wishful thinking until conclusively proven otherwise.

Paul Bamford (aka Gummo T)
Editor
8 years ago

The two stand out points for me in this post were:
– Your mental state influences the behaviour of your immune system (already well known);

– Kids in adverse social environments cope better (and suffer fewer adverse long-term consequences) if there is at least one person in their lives they can trust. That’s also well known, at least to mental health professionals – especially those who specialise in working with kids.

You don’t have to go to the extremes of Rumanian orphanages, or even the Holy Roman Emperor Frederick II’s language deprivation experiment to find examples of people whose childhood social environments will lead, or have led, to problems for themselves and society as a whole in later life.

Focussing on such examples as extreme and unrepresentative is also something that’s been around since the year dot – usually turning up as the rhetorical equivalent of Pontius Pilate’s bar of soap. Doesn’t happen much, tragic but inevitable part of the human condition…

Paul Bamford (aka Gummo T)
Editor
8 years ago
Reply to  Ingolf Eide

That’s something I find fascinating too – well sometimes.

On the other hand, I’m pretty blase about gene expression in the immune system – I suspect a fairly large percentage of the human genome is devoted to it (based on 4 decades old knowledge gained in a B Sc) so it doesn’t come as a shock to learn that 131 genes are involved in controlling the inflammation response.

john r walker
john r walker(@annesanders)
8 years ago

This report is of some interest to this discussion.

The relationship between genotype (code) and phenotype(interpreter of the code) is a bit more complexly intertwined than in the standard teaching model.

john r walker
john r walker(@annesanders)
8 years ago
Reply to  john r walker

The genetically identical twins where ” One girl was quite normal. The other had two vaginas, two colons and a spinal cord that split in two towards the bottom of her back.” is pretty thought provoking.

john r walker
john r walker(@annesanders)
8 years ago
Reply to  Ingolf Eide

yes genetically equal but radically different phenotypes at birth is not something I would have thought possible – the genes and the womb environment were for both twins identical. So how come such a radically different outcome?

conrad
conrad
8 years ago
Reply to  Ingolf Eide

A lot of this debate is basically ending up like a glass half-full versus glass half-empty debate, or indeed a Western psychology vs. Buddhist psychology account of behavior.

As much as it is nice to point out that you can find great differences in some things even in identical twins (or clones), there are also many things where you can find great similarities over groups of twins (like for example, height, VO2 max and any number of other fairly easy to measure things). I don’t think the former of these challenges the idea that twin research is useful and that lots of things have a big heritable component. In addition, no-one is disputing that you can find individual cases where gene expression has changed in one and not the other twin which has then caused a large difference in any number of things — this sort of thing is common enough and it’s well known that, for example, various environmental pollutants can cause it.

conrad
conrad
8 years ago
Reply to  Ingolf Eide

Ingolf, the reason I posted it is that a lot of this stuff is biased. For example, the last sentence you gave is “A small change in a single cell early in development could end up affecting many organs in the resulting adult, for example.”. I realize the context of which it came, but a good question to ask, which anyone can do, is that even with things like the twin differentiation effect, has anyone actually met any identical twins that were massively different? Since the answer here is generally no, we’ve basically learnt that the effect of many of these things is basically small. So examples like the one given are, in fact, very rare (and often not portrayed as so). The original article I was complaining about is biased like this.

Indeed, if you look across a life-span, you’ll find that identical twins actually become more, not less similar, even though the number of genetic differences and the number of differences in genetic expression could of course only have increased over time. This basically tells us that a lot of the stuff reported is, basically, over-hyped in terms of our understanding of the way things work — a decade or so ago, we were still getting told how important single genes were to complex behavior, but because that’s obviously false, now it’s moved on to gene expression instead. This is not to say that individual cases and strange situations that cause different expressions arn’t interesting.

As for the different types of psychology, obviously this is simplistic, but many areas of Western psychology love to find broad generalizations, the main important factors in things and so on (just think of the 5 factor model of personality). If you look at some Buddhist psychology (not that I’m an expert in it), the focus is different, and the conceptualization means that things like individual differences and the multitude of experiences people have had are much more important to understanding behavior (this is much more similar to some types of qualitative psychology). So the idea of fractal effects on behavior, which are ignored in most psychology literature, becomes important (as a side note here, Derek Parfit uses this idea to very good effect in philosophy when discussing the non-identity problem, although as far as I can tell, it is almost never considered in most public debates where it should be important).

If you’re interested but don’t like reading dull textbooks, Herman Hesse was basically obsessed by non-Western psychology, and that is part of the reason he got his Nobel Prize in literature (although personally I found his Magnum Opus, The Glass Bead Game, pretty dull), and these ideas appear in a lot of his writings. The most famous book he had where this sort of stuff appears was Steppenwolf, although I think it is mainly so because hippies liked it for different reasons (basically drug references).

conrad
conrad
8 years ago
Reply to  Ingolf Eide

I agree. Sorry if I am terse of late as it’s grumpy season for academics right now :) .

I’m not sure what the general explanation for things like IQ becoming more similar across age is, or indeed if there is one people generally are agree on. I imagine part is due to early learning having big measurable effects that then maximize out later, so even if twins get quite different environments, they can still max-out at similar levels (but at different times). For example, there are aspects of literacy and mathematics that you can start teaching at quite different ages that initially give you big improvements. But even if you learn them relatively late, it doesn’t make much difference, since most people end up doing them fine (e.g., reading ability). Thus early learning effects can cause big differences that evaporate later. There are also things like twin-differentiation effects which would wear off the longer twins are not living together. However, these might explain some of the reasons you see in the differences from early->mid life, but they don’t explain the mid->old age data.

john r walker
john r walker(@annesanders)
8 years ago
Reply to  Ingolf Eide

The interesting thing is that studies of genetically identical twins that have been, for whatever reason, raised in different environments , has been one of the corner stones of ‘nature vs nurture’ studies.
And I dont think that the suggestion that changes to the genome after conception might sometimes be inheritable is Lemarkian.

PS Conrad re Buddhism are you referring to all three of the main schools of Buddhism?

conrad
conrad
8 years ago
Reply to  Ingolf Eide

John, my reading is far too limited to be able to distinguish who is currently thinking what and how different strains of non-Western psychology (or in fact understanding of behavior) relate to each other. I wish I had more time to read that sort of stuff and really get to know differences in predictions and so on between the groups.

john r walker
john r walker(@annesanders)
8 years ago
Reply to  Ingolf Eide

Conrad
The Mahayana Buddhist tradition is a very broad sangha , has a very pragmatic attitude to methods of achieving enlightenment – if it works , good.

Sancho
Sancho
8 years ago
Reply to  Ingolf Eide

Principles of zen are making their way into mental health care, in Australia at least.

Look into mindfulness and the Smiling Mind program as examples.

john r walker
john r walker(@annesanders)
8 years ago

Morning mist, how nice,
just for once
not to see Mt Fuji.