Physiological evidence has emerged that the care a mother offers her infants can re-set how the offspring respond to stress. The more care, the lower the levels of hormones like adrenaline in reaction to stressful circumstances.
Norman Swan: Physiological evidence has emerged that the care a mother offers her infants can re-set how the offspring respond to stress. The more care, the lower the levels of hormones like adrenaline in reaction to stressful circumstances.
The trouble is that at the moment the findings are in laboratory rats. But according to one of the researchers, Professor Michael Meaney, of McGill University in Montreal, it's at least in part applicable to humans, since a fair bit is known already.
Michael Meaney: It's certainly known from human and studies with monkeys that maternal care is relevant for the development of the animal's ability to deal effectively in behavioural or hormonal terms, with stresses. What wasn't known particularly was exactly how these effects are represented in the brain, exactly how is it that maternal care regulates the development of the brain and in turn regulates the way in which animals respond to stress over the course of their life-span. And that is particularly the focus of this study.
Norman Swan: So you looked at really what happens when - and this was particularly rats - what happens when the mother grooms her child.
Michael Meaney: Exactly. When you look at licking and grooming in the context of an interaction between a mother and her offspring in the rat, that's the principal form of physical contact. I suppose in the loosest terms, it is the rat equivalent of caring, holding and handling one's offspring.
What we did, very simply, was to look at the offspring of mothers who showed more licking and grooming towards their pups, or less licking and grooming towards their pups, again the analogy here being towards greater or lesser degrees of physical contact between the mother and her offspring. We then did what one would ideally like to do in these circumstances, is to follow the offspring through to adulthood, and what we found in fact was that the amount of licking and grooming the mothers afforded their offspring during the first ten days of life, actually correlated very strongly with both the behavioural and the hormonal responses of these animals to stress.
Norman Swan: Before we get to the behavioural, what were the hormonal responses to stress?
Michael Meaney: What we're looking at in particular is the production of classes of stress hormones. These are the catecholamines, most commonly known as adrenaline and noradrenaline and the glucocorticoids and these are the hormones which basically mobilise the body in order to allow it deal successfully with the challenge of a stressful moment.
Norman Swan: The glucocorticoids are the cortisone-like hormones.
Michael Meaney: Exactly.
Norman Swan: So a rat pup which had had a lot of grooming, versus one who had a little grooming, had a lower level of response to stress hormonally.
Michael Meaney: Exactly. And I'd like to emphasise that the animals' response was certainly adequate. It was somewhat more modest and the interesting thing --
Norman Swan: In other words, they weren't going to die as a result of not responding to stress.
Michael Meaney: Absolutely. There was nothing inefficient or insufficient about the animals' response. And what's I think most interesting here in terms of health, is that the magnitude of the stress hormone response to individual challenges, correlates if you will, with the demand of these challenges on the individual's health. That is, the more stress hormones you produce, the greater it's likely to compromise the health of your cardiovascular system and your metabolism in general. So in fact what you really want ideally is an animal and an individual that produces an adequate or stress hormonal response, but one that is not exaggerated, and that was typified by the animals who were the offspring of mothers who showed greater amounts of licking and grooming.
Norman Swan: And what about the behavioural effects?
Michael Meaney: Well the behavioural effects lie very much along the lines of straight fearfulness. The animals who were the offspring of mothers who showed more licking and grooming were much less fearful, much more curious, much more exploratory. In contrast, the animals who were the offspring of mothers who showed less licking and grooming were more timid, more withdrawing and more fearful when confronted with novel situations.
Norman Swan: Isn't it possible though that you've got horse and cart problem here, that there might be something genetically in the offspring of mothers who don't groom a lot, and that they might be predisposed genetically to a higher level of stress and it's nothing to do with the grooming whatsoever.
Michael Meaney: That's entirely possible, or was entirely possible, yes. I agree, that's a very logical conclusion from the study that you've actually looked at. What we've managed to do since that period of time is to show that in fact that we can do via either adoption studies, is to show that in fact these are traits which are inherited, but that it appears that at least in part, the mechanism of inheritance is not dependent on the genome. That is, if we take the offsprings of a mother who is otherwise a low licker and groomer, and transfer those offspring to a mother who is high licking and grooming, that those offspring in fact then come to resemble the mother who is the high licking and grooming animal. So that it is not dependent, if you will, on genetic inheritance, it's more a matter of inheritance, at least in part, that is behavioural in its origins.
Norman Swan: For those of us who have no idea really about a rat's natural life-span, can you just translate in terms of childhood, mid-life and late life, the first ten days, and indeed when these behavioural effects to stress first appeared?
Michael Meaney: Right. I can do this obviously with the caution that species differ dramatically, the old notion that one year of a dog's life is the equivalent of seven in a human's is largely a fallacy. But to give you some idea of the landmarks. That if you were looking at what would be the human equivalent in terms of brain development of the first ten days of life, it would be somewhere around the first six to twelve months of life. And as to when these differences appear, they seem to appear at about what would correspond to adolescence in humans. And I think that in general, when you look for instance at the consequences of various perturbations in parental offspring interactions in humans, that they usually become apparent by about the time the child is beginning say, primary school or somewhat there around.
Norman Swan: Have you tried intervening in rat adolescence to see if you can reverse these stress changes?
Michael Meaney: Well as a matter of fact that's the obsession of one of my graduate students who has very recently presented a paper on exactly that. And I think this is something that's really quite interesting. What she's working with is in fact is something that is I suppose more emblematic of a clinical situation, and that is long periods of maternal separation in young rats. Long periods of maternal separation in rats or in primates and anecdotally in humans, produce animals that are excessively fearful and highly reactive to stress. And what she did was to take those animals in what would be the adolescent stage of their life and expose them to an extremely enriching condition, full of playmates and forms of stimulation, and was able to very largely reverse these effects. So that the animals that came from this particular environment's enriched condition, showed none of the abnormal behavioural patterns characterised by the increased timidity that you would come to expect from long periods of maternal separation. So there is at least some optimism that I think these things are reversible.
Norman Swan: Why would an action like grooming or cuddling a baby re-set - and that's the implication here, is that you've got genes for these stress hormones and presumably there are people in the world who have genes which are more twitchy or are predisposed to produce more stress hormones than others - what's the mechanism for grooming re-setting, that gene that might have a high propensity down to a lower propensity to produce hormones?
Michael Meaney: OK. One of the things that I think we tend to often think about genes is that they are, if you will, the unalterable or immutable by-products of inheritance. Either you inherit a gene or you do not, and that's it, and if you inherit it, then this gene will play itself out and its influence will be felt throughout the lifespan. That's not entirely true, in fact. Genes are molecules, and like other molecules they are subject to regulation by environmental factors. To give you an idea: the structure of the form of a gene influences greatly its level of activity, and in part at least, we have evidence that the genes which are responsible for controlling the stress hormone response during a period of stress, are in fact regulated by maternal care, and the level of activity of these genes is determined by the level of maternal care, and in fact this is a way in which the environment, if you will, almost programs the activity of these specific genes throughout the entire lifespan.
When you look at a rat, or by analogy, in the human, the animal for the most part learns about its environment in relation to its interaction with early caretakers, that, if you will, the developing animal's world. And what I think is actually occurring (and underscore the word 'think' here) is that the early environment is if you will programming the tendencies of the animal to respond either in a very reactive way or in a somewhat less reactive way. And I'll give you an example of what we think is going on here. If you were the offspring of an individual growing up in an environment which was highly impoverished, full of many sources of infection and disease, then it is in your best interest to have a very highly reactive hormonal response to stress, because you're going to need it; you're going to need it to ensure your survival in the short term across what is going to be a very demanding, very challenging and very endangering environment. If on the other hand you happen to grow up in an environment which is somewhat more characteristic of the Western world, where food is somewhat more plentiful, where the society provides a measure of care for you and in general life is not perhaps quite as demanding as it might be in more impoverished areas, then the need for you to have a very reactive hormonal response is not quite as great. And what I think is happening here is that the early environment through parental interactions is basically guiding the development of the brain to, if you will, create biases and tendencies to respond in one way or another, and generally these tend to be very adaptive.
Norman Swan: And the $64 question, which is, how applicable is all this to humans?
Michael Meaney: Well I'll tell you. I'll take you through what we know of the story that we're attempting to put together, and that is as follows:
The early environment regulates the activity of the specific genes in the brain which in turn influences hormonal and behavioural responses to stress, which ultimately then influences vulnerability to disease. Well we do know that amongst humans, individuals who show a greater reactivity to stress, people who produce much higher levels of stress hormones during periods of stress, are at greater risk for the development of heart disease, diabetes, depression, drug and substance related abuse problems, etc. That part is well established in humans.
Norman Swan: Do we know about maternal care and stress levels?
Michael Meaney: That's the second part and in fact actually that part seems to hold reasonably well also. We know for instance that individuals who are the by-product of abusive or neglectful homes are much, much more reactive to stresses. And we believe the link here is very much in terms of altering the way in which these individuals respond to stress. So at least in terms of the evidence that has been mobilised on the human front, it is very consistent with this picture that's been developed in the rat.
Norman Swan: So lots of licking and grooming in post natal wards across the nation.
Michael Meaney is Professor of Psychiatry and Neurology at McGill University in Montreal.
Liu D. et al. Maternal Care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 1997;277:1659-1662
- Dr Norman Swan