October 19, 2009
Animal Kingdom: Lessons Learned
Introduction: Welcome to "Speaking of Science." The National Institute of Mental Health presents a series of conversations with innovative researchers working in a wide range of disciplines to pave the way for the prevention, recovery, and cure of mental illness.
Dr. Insel: This is the first in a series of conversations with individuals who come for talks here at the NIMH, particularly within our Innovation Series. And we are delighted today to have Dr. Robert Sapolsky, who is a professor at Stanford University, with a long history of research in neurobiology and psychobiology, including a great tradition of field studies in human and non-human primatology. One of the things we are hearing about a lot is the idea that stress could leave a sort of footprint that you could find years later. You mentioned before that stress during fetal life, or early in development, can sort of set up a pattern in terms of metabolic homeostasis, or put somebody at risk for instance for diabetes later. Is there a way that you could begin to look at that? Is there a footprint that would be present biologically, that you could take out a blood sample from someone, or look at their genome, and figure out that this is a person who has been scarred by a particular exposure during fetal life, or early in development, and even do that years later. Is there - are there tools for that?
Dr. Sapolsky: You've got your genes that produce proteins. And rather than this picture of genes being autonomously running the whole show, there are switches for them, turning them on and off at appropriate times. And there are mechanisms in which events in the environment can in effect freeze some of these switches on, or freeze them off. And what is now beginning to be realized is some of these ways in which early experience can play out in the whole lifetime is in ways of if not disabling certain genes, certainly making it harder to use them in the future, or conversely over-activating some of them stress has a means to gum up some of the switches for long after.
Dr. Insel: And so those are things you could actually detect, and see basically -- like a footprint or a fossil. You could say Ah! Somebody has actually got the residue of an experience.
Dr. Sapolsky: Or maybe even an apter term would be molecular scar tissue of your adversities.
Dr. Insel: What allows some people to cope better than others, and what are the things that any of us can take from the biological literature, from how through evolution coping takes place that might be of value for us to remember during tough times. I think it was only last night that the president said how do we turn ordeal into opportunity? So what's your thought about the opportunities for coping?
Dr. Sapolsky: Well, again if we are distinguishing between the world of "these are stressful times -- I am going to wind up on the street" versus "these are stressful times in a purely psychosocial way" concentrating on the latter its turfing back to this world of few of these stressors will shorter your life expectancy, few of these stressors will lead our bones scattered on the savannah while predators pick over the leftovers. Instead they are psychosocial inventions. And there is the potential to very powerfully manipulate the psychosocial settings. Again from the same external misery, you are more likely to subjectively feel stressed, more likely to activate a stress response, more likely to get a stress-related disease if you feel like you have no control over what's going on, if you feel like you have no predictive information - when is it coming, what's going on, how long is it going to last, how bad is it going to be? If you are set up to interpret things as getting worse, if you lack outlets from the frustration, if I you lack somebody's shoulder to cry on, social support. And to the extent that one has to fall back on homilies, you know, give me the wisdom to tell the difference between what I can change and what I can't, you don't want to try to control the uncontrollable, you don't want to try to control something that has already occurred. But within the realm where it is realistic, little footholds of control can be enormously helpful. Understanding which outlets are most efficacious, understanding that above all else, we are a social primate, and the support derived by that - again it potentially sounds platitudinous, but these are when they are varying, when they are manipulating an order of magnitude some of the biological outcomes to these things, these are no mere platitudes.
Dr. Insel: Is there a difference between men and women, in terms of vulnerability?
Dr. Sapolsky: There is in a lot of realms, and not surprisingly it's a complex and often contentious field. In lots of ways, where some of the most important differences play out biologically are the ways in which testosterone is not a hormone you necessarily want to have around for your cardiovascular system for example. And the ways in which estrogen is a very desirable hormone to have around. So that's a big difference. And that certainly plays out in terms of, for example, some of the vulnerability to growth disorders during chronic stress there's some gender differences. Where the most meaningful sex differences come from I think is more at the psychological and the psychosocial end. And this is, you know, potentially barreling into all sorts of clichs, but one that is nevertheless supported by the literature, women are far better on the average at taking advantage of social support and emotional outlets than are men on the average. And particularly so doing aging and the responses to stressors at that point, that's an area where there's big differences in coping skills, emotional expressivity, interdependence, all that sort of stuff, very striking differences.
Dr. Insel: What's been the most helpful in your trying to understand the vicissitudes of human psychobiology?
Dr. Sapolsky: I would say, and this is going to be fairly undefined, but just realizing the extent to which all this biology and neurobiology and neurogenetics and all this cutting edge stuff, the extent to which it makes no sense outside of the context of environment, and experience, and how some of the most interesting parts of the brain are exquisitely shaped by the world around you, and the extent to which the genetics of stress and psychiatric disorders are the genetics of vulnerability rather than inevitability. And that's actually possible to start understanding how this works.
Dr. Insel: Thank you very much for joining us. This has been a really a terrific conversation. A lot of the work you are doing currently which is veering off into a new realm of looking at the role of parasites in regulating the stress response and regulating behavior is going to open up a whole new door, and we'll have to have you back at some point to talk with you more about that. Thank you.
Dr. Sapolsky: Thanks.