>> From the Library of Congress in Washington D.C.
^M00:00:05
[ Silence ]
^M00:00:23
>> Good morning.  We're going to have a wrap up of yesterday today.  And I thought what I was going to do, I saw the talks yesterday, I have taken notes, I can summarize them.  But I think I don't have a feel of the cards for what really is of the essence of the work of what these individuals are doing.  So I thought what I would do since most of them are here except Dr. Clauw, and I'll summarize his, is I would ask each of the people who had spoken yesterday to come and spend five minutes or so giving what they think is the essence of what they have to say and where they think it might be going.  And I think, they'll be able to do it better than I.  So I'll start first with George, you want to come up here and do it?
^M00:01:04
[ Pause ]
^M00:01:14
>> Well Phil, you know very well what I discussed yesterday.  And basically, it was an introduction to the concept of stress as disturbance in our steady state homeostasis.  And how this disturbance can damage our tissues, including the brain, and the periphery in the body.  And it's interesting that the same hormones or modulators that help us deal with stress in acute type of you know, stressful situation.  When it's chronic, the same hormones, the same modulators produce the damage.  Starting from the brain where usually what you get is a hyperactive stress system but you can get the other way around and also the hypoactive stress system.  And with everything that this entails from a behavioral point of view.  In the body, the key thing is what chronic stress does to visceral fat which is increased to loss of muscle or sarcopenia, loss of bone or osteoporosis.  And the result in atherosclerosis from the metabolic alterations that chronic stress produces.  It's interesting that people who are chronically-stressed have a pattern of cortisol secretion that's blended at circadian rhythm.  Meaning that in the morning, it's a little lower, and in the evening, a little higher.  And because our tissue sensitivity to glucocorticoids changes during the day and it's most, it's at its highest in the evening when also in stress people cortisol is elevated, went up with the chronic effects of cortisol which is actually metabolic syndrome.  That well-known disease, Cushing's disease or Cushing's syndrome or hypercortisolism is just cortisol-induced metabolic syndrome.  Loss of muscle, collection of visceral fat, insulin-resistance, dyslipidemia, hypercoagulation of the blood, chronic smoldering inflammation, destruction of the endothelium and the blood vessels and death.  Also, chronic stress, it can influence carcinogenesis, for two reasons.  Number one, inflammation by itself is carcinogenic, so if a cell has high NF-kappa B and other mediators of inflammation.  This cell is, has a higher probability to become cancerous, and second is because of the effect that chronic stress has on the immune system.  And the general effect of stress is to suppress innate immunity and to switch T cell immunity and humoral immunity from left to right.  In other words, people who are stressed have decreased cellular immunity and increased type II humoral immunity.  Therefore, chronic stress will predispose somebody for diseases of the type II immunity such as allergic disorders, such as asthma.  Needless to say that stress, especially intermittent stress, has been associated also with type I immunity problems.  And atherosclerosis is one of those.  Atherosclerosis type I, cellular immunity type of problem.  In addition, rheumatoid arthritis, lupus and other autoimmune conditions are affected by stress.  Sometimes, stress is protective and frequent stress is producing vulnerability in the people to express the disorder.  That's it Phil.
>> Thank you George, that's great.  George let me ask you this question.  It seems that in all of these syndromes, inflammation say, is central and the other components, modules that click in you know, in terms of the stress response, central components, peripheral components.  But I wondered, why is it do you think that, in terms of stress, some individuals develop one disorder and not the other?
>> I believe that as Dr. Wadhwa mentioned yesterday, vulnerability is defined by genetic and epigenetic or environmental reasons, constitutional reasons.  So if you have a certain vulnerability, genetic, epigenetic and you find yourself either with an increased activity of the stress system, or a decreased activity of the stress system, you can express the corresponding disorder.  So each one of us have some vulnerabilities, and depending on those stress, it can have a different effect.
>> And so, do you think that the fundamental alterations in the stress system are relatively similar across all of these disorders, but that there is an accentuation of one component or the other, that results in expression?
>> Yeah, that's exactly what I think.
>> So that across the whole spectrum--
>> Across the whole spectrum, yes.
>> --that there's a common thread that gets expressed.  Okay.  Good, thanks George.  The next I'll call upon Philippe if he could summarize for five or six minutes.
>> Okay.  So, I said a number of things but here are some crystal, crystallized essences.  The quality of our attention is the basis for emotional awareness, emotion regulation ability, empathy and then finally compassion and in compassionate or altruistic behavior building on the quality of attention.  That's one key point.  Attention, all the different forms of attention are trainable.  And they manifest as in circuits in the brain that we can actually begin to examine in which different forms of attention, emotion awareness, emotion regulation aren't instantiated.  We can see that with neuroimaging tools.  And the brain circuits, the weights, the nodes, the connectivity itself, as in addition to just the grey matter volume, is modifiable, trainable.  So what we choose to do every morning when we wake up, literally sculpts, the brain, and its connectivity.  Hence, we have a huge responsibility to understand this research laboratory.  The ultimate research laboratory for which you don't need a single grant, a single penny.  Why is this important?  The entire central nervous system, the peripheral nervous system is under the control of the brain.  The brain is under the control and we, human animals because we have a view of self, thinking, self-inquiry, self-reflection, we could actually modify our experience.  Concretely, there are many, many, many stressors.  Even if you don't have anxiety disorders or depression or eating disorders, et cetera, et cetera.  We live in chronic stress.  It does nothing wrong with that.  In fact, that is the grip that allows us to use our incredible ability to think, to feel, to consider and to reflect.  So in fact, that's probably what stimulates us to be human, to really work with ourselves.  So there's nothing wrong with stress or anxiety, or depression.  It's how we then respond to it by taking the challenge to think in a certain way.  And so a few things I did not mention yesterday but Dr. Gold and I just mentioned a moment.  I have a whole different line of research on view of self, in people with anxiety disorders and how different forms of psychosocial interventions modify brain circuits.  And I mentioned that because the view of self, my view is that it really supports the patterns and profiles of emotional reactivity in each of us.
^M00:10:02
And also influences how much we actually use different top down regulation strategies.  Be it attention regulation, cognitive perspective taking, or suppression or even metacognitive skills that we can develop.  There are many, many, many tools for training the mind.  Mindfulness meditation is just one type.  Aerobic exercise can be powerful, cognitive-behavioral therapy can be powerful.  There are many, many different kinds of mental trainings.  And just in the same way that there are proclivities that allow us to, that become vulnerabilities to develop depression, anxiety, bone loss, different immune diseases.  Likewise, we have different proclivities towards different forms of trainings of the mind.  So the responsibility, I go back to that word is for each of us to experiment, be a scientist, discover which methods really, really work at which point in your life as a child, as a parent, as an older adult, to really continue to sculpt the brain, the mind, which are completely fused and plastic, and malleable to invite stress as a tool, as a stimulus to use, in most human capacities.
>> Thank you.  Let me ask you a question.  If you see a patient with severe melancholic depression who's clamped in this anxiety about self, this feeling of worthlessness, and given the organization of the brain that the amygdala, in a sense you know, an enormous plethora of fibers in the cortex.  But the cortex isn't really relatively unable to speak to the amygdala.  How you can modify a disorder like that using the methods that you described?  And it's clear to me when we spoke that you are able to do so.
>> Yeah.  So, what Dr. Gold is mentioning is that, clearly there's a--communication has to happen across all these different brain systems.  And these are psychological systems.  Be it anxiety or melancholy or different forms of suffering, there's a breakdown in communication.  And it is very well documented when there's a huge amygdala, emotional reactivity, there are times when both the tension, prefrontal cortex, thinking, cognitive ability, specifically dorsolateral prefrontal cortex, dorsomedial, and those visualizing brain systems are inaccessible.  So that's actually amygdala hijack and being stuck.  So the question is how can you break through to open that, a conduit, to these resources that are already in the brain.  So one, I mean clearly for, there are many methods to work with you know, deep depression.  In some cases, cognitive therapy, thinking strategies, but that really, that's not the easiest thing when you're really, really stuck.  In initial stage, it might be literally getting somebody up and out and aerobic exercise, out moving.  That's one step.  Then cognitive, when that becomes accessible, thinking in a way, getting a person out of the distorted view of self just enough to be able to take a different perspective than the one that I've been sitting in for the last six months or six years, or 60 years, you know, deep depression.  Another thing is allowing the person to actually experience pleasure, food, exercise can be pleasure.  I have friends of mine, but many people who are actually trying to study how you can--let a person with depression experience pleasure in a way that becomes palpable so they can actually expand the field of view from just as, to start to view himself, to start to view of the world, to start to view of the future, not this horrible triad in depression.  Mindfulness meditation is not for people with major depression.  For anxiety, yes.  Not for depression, clearly, it's not a treatment for depression.
>> Right.
>> You know, it's interesting that it's something like exercise which really recruits so many components of the central nervous system.  And ECT which does the same thing, I'm not saying that they act necessarily in the same way, but somehow, you kind of resynchronize the circuitry by applying a profound stimulus that takes thinking and all of the physical elements that are involved in exercise.
>> Yeah, just like resetting, sometimes, you can even think about jolting the system.
>> Jolting yeah.
>> Kind of breaking things up a little bit.  So there's a little more fluidity, a WD-40.  Now, you know, they used in the last, I'll stop because we have to go on.  That 30, 40 years ago, one of the strategies that did work also was putting people to sleep for seven days.  And they couldn't do it safely then because of the problems with respiratory difficulties and aspiration.  But something that as you say, jolt the system, can be many different things, okay.
>> Thank you, that's so wonderful
>> Roberto, if you could speak for just a moment.  I think you've--both, all of you are doing much better jobs than I would.  And this is a way to do it.
>> Great well, thank you very much to all of you.  Carolyn, for the invitation to come.  I would like to convey five messages.  The first one is intrauterine life is far more rich than we generally believe and I demonstrated yesterday physiologic functions that also show some hints that there are some behavioral expressions during intrauterine life.  In the context of stress, I would say that the stress of being born, this is evidence that is substantial by measuring catecholamines that is also, has a beneficial effect.  And the beneficial effect is number one, it favors the clearing of lung fluid.  Number two, it prepares us metabolically for a state in which we are continuously being supplied by the placenta.  And when that umbilical cord circulation is interrupted, we need to have a means to maintain nutrition, and that is the endocrine system.  And thought, we, that stress prepares us to a transition from a state of sterility where there are no bacteria or viruses, to one in which we are continuously exposed to bacteria or viruses.  I think that these are point that I want to make is, when that stress, that physiologic stress does not take place, then there is increased risk for short-term disease, transient tachypnea of the newborn.  But now, we know from patients who are having elective cesarean section without labor, that there maybe an increased risk for diabetes type I and for asthma later on in life.  The last point, these are--there is pathologic stress and that is the one that is inflicted by pain, by inadequate nutrition and also by infection.  All stresses that occur, at least, nutritional deprivation and infection frequently during intrauterine life can lead to short-term and long-term consequences that are deleterious.  So those would be the key messages of my talk.
>>And Pathik is here, if he could do the same?
^M00:17:41
[ Pause ]
^M00:17:49
>> Good morning, thank you.  So, I think this is an interesting exercise trying to, on the spur of the moment get us to.  [Laughter]  But I think, I think the two sets of things that I wanted to say, the first was to pick up on the--all your speakers from yesterday who discussed the consequences of the nature of the environment we live in, particularly if it's related to challenges and stressors.  The consequences of that for health, so the first point I wanted to make was, those consequences seem to be profound when one considers those effects in the context of fetal life and intrauterine development.  They seem to be larger effects and they seem to be more long-lasting.  So, that seems to a period of time, the time when an individual is developing, when conditions in the environment such as stress have the potential to exert more potent, more long-lasting effects.  So that was one sort of thing.  But then the other thing I tried to talk about, I think with relation to stress was this notion that, unlike non-living entities that somebody else puts together, and constructs.  Living entities play an active role in their own construction.  They play an absolute obligatory, active role from the very earliest or time point which is fertilization.  Part of this activity seems to be directed towards acquiring information about the nature of the environment in which they're developing, and then using this information in some ways to shape various aspects of their development, both structurally as well as functionally.
^M00:20:02
Within limits, I mean, nobody is going to develop generally 12 or 20 fingers.  But there is a lot of structural variation within different cell and tissue types in this enormous functional variation.  And the setting of this seems to be something that a developing organism actively participates in doing, using information about the nature of the whole of his environment.  I tried to say that if one asks what aspects of the environment, then I suggested that there are two aspects that may be particularly important that a developing organism is looking at.  The first one relates to the availability in other aspects of energy substrate on nutrition.  Living organisms cannot synthesize energy and need to acquire it.  And, so where is the energy located, in what form, how intermittently does one get it, what is the composition?  All of this is something that a developing organism is actively looking for information about because this has implications for how she or he wants to modify their systems to most efficiently capture it.  The second set of circumstances that a living organism is looking for information about is what other conditions in the environment that pose a challenge or a risk in terms of either survival or reproductive success or more technically survival until the age of reproduction.  That's the major concern.  It's not a concern after the age of reproduction.  So, so challenges that inflict a large burden of mortality and morbidity particularly in childhood years such as certain kinds of infectious environments or the presence of predators would have been a condition that--so you know the way we might translate that into certain sorts of risky environments now, not literally predators.  Those would be cues that an organism is looking for incorporating in its construction on development.  And the final point I made was that the stress system happens to be a particularly attractive candidate system in conducting this process.  So the stress system is more than just the effects of stress on health and development.  It seems to be a key of system that the brain and periphery use in detecting not only conditions related to mortality, morbidity but even I was suggesting conditions related to energy substrate because it's the stress system that plays a role in redirecting energy.  The basic--if one were to ask, I don't know if George and Phil would agree but if one were to ask in a single sentence in a few words, what is the key role of function of the stress system?  I would propose that it's redistribution of energy across various components.  So if that's the case and if energy is what we're looking for in terms of how do I fine tune my development so that I match the energy substrate, then really, the role of the stress system in development is larger--includes but is larger than just detection, often responses to "stress."  So, I don't know if this makes sense but that's what I was hoping to try and ramble on and so I'll stop rambling that.
>> I think that's great.  I agree with you.
>> Thanks.
>> Yes.  Thank you, and Lorah?
^M00:24:00
[ Pause ]
^M00:24:06
>> Thanks Phil.  I think I have probably three points I want to address.  First, I was glad that adolescents were included in this conference.  Obviously, I think it's a pretty key time period but I hope you got a flavor of that too.  The first key point is I think that adolescence is really a vulnerable time, potentially for some individuals.  And I think Dr. Chrousos mentioned again this morning about how it's not all individuals but there is probably a genetic and constitutional aspect to that.  So it's not all adolescence that bad things happen too.  In fact, it's, you know, probably less than 20 percent or so that go through with really more of a dramatic kind of time period in that lifespan.  Biological transitions are really a key period and adolescence is that biological transition.  I think that can be a period that adolescents are set up and I mean set up either for failure or for success.  So it's not always set up in a bad way but they are set up because that's a time of gaining knowledge, gaining strength but it's also a time with peer pressure and all of those other sorts of things.  So if you can get the right balance, there could be success.  So I don't argue that the prenatal period isn't important but not--we're not going to hit every prenatal kid to make them perfect.  So in adolescence, maybe we can take over from then.  The second thing is I hope you saw that the stress axis does seem to either play a role in this whether it's a cause or a consequence in some of these adolescent conditions, it's not clear.  I gave you the example of dysfunction or dysregulation of the HPA axis for Romanian orphanage children, the child trauma, the maltreatment abuse, that sort of thing, but also thinking about differences in context.  So for example, I showed you that the parent marital relationship and mental health mattered for what a kid's cortisol did.  Gender made a difference and also the foster care, whether it was regular foster care or an embellished foster care really made quite a lot of difference for that.  So, there is the chance for intervention during this period.  So if we pay attention to this period and think about both what can we do within families, what can we do with the neighborhoods and schools, the broader environment of adolescents.  I think that can make a potential difference.  So some famous person once said, "It takes a village to raise a child," so--and I won't tell you what bumper sticker is still on the back of my car, hint, hint.  [Laughs]
>> Lorah, thank you and that's terrific.  In my talk, I talked about the--how the dysregulation of the stress system could result in the behavioral and physiological manifestations of a disorder like a melancholic depression and atypical depression.  But from listening this morning, I wonder, you know, in a sense, you know, since the brain derive a problem and all of this are certainly, have the CNS involved.  The depression is a pleiotropic, complex disease.  You not only have the behavioral alterations but patients with depression have a metabolic syndrome even though they're not obese.  They have osteoporosis even though they don't have risk factors that are necessarily common except perhaps hypercortisolism and increased burden of inflammation and so forth.  But for some reason, all of these manifestations seem to occur in a single individual if they had multiple vulnerabilities.  And maybe, that might be one of the reasons.  It's hard really to get a handful on depression because there's so many genes that might be involved in this pleiotropic syndrome.  It's difficult to just isolate just one or two.  The other point I would make and this gets into then-clause talk is that it seems to me that the anti so-called antidepressants also have pleiotropic effects that they're useful not only in treating say a syndrome like a melancholic depression or other forms of depression but they're helpful say for instance in some of the fatigue states that Dan talked about.  And they're helpful in the treatment of another disorder that has a lot of comorbidity with depression migraine disorder.  And that each of those, a cohort in any way and then perhaps they may share more, involved in the complex genetic disabilities, you know, response that has one common denominator in that some of the patients in each of these responds to what we call traditionally, an antidepressant.  And we need to understand perhaps more that people are studying in a sense, the mechanisms of action of antidepressants that the only ones we have are the ones we can study at this point of the people looking into theoretical systems like the glutamate system.
^M00:30:00
But that--in wondering how these--how these drugs are influencing--what changes in the central nervous system that they're causing that they influence mood that they can influence pain, that they can influence metabolic function, and so forth.  And, you know, and David Spiegel who is here today showed that, in addition to the--the efficis to all of these conflicts, is where stress plays a role in the progression and even of metastatic cancer.  And each can modify the survivability in women who have metastatic breast disease by having them participate in support and psychotherapy groups.  The other issue is that exercise seems to be effective across the boundaries of some of these disorders, depression say, and the pain disorders.  And good nutrition also seems to be involved.  You know, when people say, and this is where I get to think about it differently, folks, when they get up and say, now, well, if, you know also exercise helps, diet helps, you know, and sleep matters.  You know, they may really matter in terms of the fundamental pathophysiology of these disorders.  And they maybe actually--for instance, this stimulates me more to do aerobic exercise now, 'cause I can say I'm synchronizing my brain.  And this is where I'm like getting a, you know, a soft--that course of ECT treatment.  But as long as I have a model anyway, you know, it stimulates me perhaps to invoke this as another way of having the salutary effect of these complex disorders.  And it maybe something more than just simply a generic, and so it's good for you, kind of phenomenon.  So I'll stop here and now we'll go on with our next talk.  Margaret Ensminger is going to talk about stress and socioeconomic status, and other potentially-related issues.  As we get in today more to the societal implications of stress beyond individual susceptibility.
^M00:32:03
[ Pause ]
^M00:32:07
>> Hi, I'm pleased to be here.  I'm Margaret Ensminger.  I'm at the school of public health at Johns Hopkins University.  And I feel like my talk builds on yesterday but is something of a departure because we'll kind of leave this wonderful research site that Philippe talked about and go out to see what society--how society impacts stress.  So I want to do three things--four things.  I want to talk something about the sociological study of stress because this is where outside factors have come under the most scrutiny and talk about the current state of knowledge in that.  And how stress manifests itself in the adverse social environment?  Now I'll use examples from my 35-year longitudinal study of poor African-American community in Chicago to illustrate some of that.  And then if we have time, I'd like to talk about some of the recent work that's gone on about how social inequality influences society as a whole, societal inequality.  So the major themes in the sociological study of stress had been--have stemmed from the study by Holmes and Rahe in 1967, in which they sort of spontaneously discovered that people in the navy who had major life events saw their doctor a lot more often and got sick.  So things like moving, death of a spouse, job loss.  If you counted up those things, you could--you could--it was very highly associated with illness and seeking help.  So the sociologist sort of took off from this.  And they began studying what they call these events as acute stressor events, but then noticed that what was termed chronic stressors were even more important.  These were things that were not acute events but were ongoing issues, difficulty paying bills, difficulty with interpersonal relationships, living in a disorganized dangerous neighborhood.  So there's then a long history then of research that has documented how those things influence not only health and well-being but how they also influence those things that protect us from stress.  And in addition or in connection with this is the thought of cumulative advantage or cumulative disadvantage.  So that idea is that if you start young with disadvantages, these things then--if you fail in school, it accumulates.  You don't--you aren't as likely to graduate, then you aren't as likely to get a job, then you're poor, then you have all the--all the burdens that that brings.  So there's the notion of the accumulative advantage or accumulative disadvantage.  Okay, I think I've sort of talked about this that major changes in people's lives lead to sickness and ill health.  The transition from the focus on acute stressors to the focus on more chronic enduring problems.  And the sociologist then began to think that acute stressors were important but what seem to really lead to more problems were more chronic stressors.  Okay, so one of the big contributions in this area of both psychologist and sociologist has been to document quite convincingly and quite with intensity and depth, the disadvantage that the poor are more likely to have in terms of the stressors that they experience.  So they have an inability to pay their bills, they don't have enough money for housing, they don't have enough money for healthcare, they have difficulty getting appropriate childcare, they live in poor environments, both physically and socially.  So they lived in--more likely to live in neighborhoods with environmental hazards.  They're more likely to have housing that's not kept up, unhealthy living conditions, their children generally go to poor schools, they have worst working conditions, and they have fewer parenting resources.  So that all has been documented over the past 30 years in great detail.  Also, what's been documented is that the poor are less likely to have the coping resources to be able to deal with stress.  So they're less able to keep up social relationships.  This maybe a little counterintuitive but I'm going to show you some data in just a second to back that up.  They have high feelings of failure, because in a society in which if you--if you work hard, you should be able to have money to support yourself when the evidence that people live doesn't support that leads to a feeling of failure.  And they have feelings of not being in control.  Partly, this is related to the kinds of jobs that people have.  So if you have a job where the bottomline is that you contribute, you control your own hours, you control more or less what you work on, you control what you do, that gives you a sense of feeling that you are in control with things.  If you're in a job where you have to ask permission even to go to the bathroom or to work on an assembly line where your job very much--I'm giving you the extreme example now--where your job is very crucial to the whole line, then you don't have that feeling of control.  So what people have shown is that what we do in our everyday lives lead us to this feeling that we're in control of our lives.  The kinds of jobs that poor people, or not even the poor people but the kinds of jobs that don't lead one to feeling in control permeates then not only their work life but their social life.  And then all the accumulations of these stressors lead to poor health which in of itself is a stress.  So here is the data I want to show you on social isolation and poverty.  So this is from a study I'm going to be talking about, it's a 35-year longitudinal study of children that we began with when they were six years old and last interviewed when they were 42.  And there's kind of a romantic image that people who live in poverty still are able to make relationships and have good family feelings.  What this data shows is that they are not as likely to be able to do that.  So we have here a comparison of those people who are poor.  Well, let's see.  A comparison here of those people who are not poor and who are working with those people who are poor and working with those people who are poor and not working.
^M00:40:02
And--I'm sorry, and if you compare these kinds of social relationships that we looked at, organizational ties, church attendance, social support from family, and social support from friends.  We see that almost without exception, the two groups that are poor, even though they're working, poor and not working, are less able to keep up the ties.  So, the only exception to that is church attendance, so those people who are poor and working.  Whereas, likely to attend church is those people who weren't poor.  But social support from family and social support from friends were less.  So, this romantic notion, I'm sure it's true for many people about this romantic notion that poor can count on family and friends, is even--that's even a disadvantage that they often need to cope with.  Here is a neighborhood variable that if you live in a white-collar community which is sort of a proxy measure for being in a middle-class community, you also are more advantaged with regard to social ties.  So this was the idea that I mentioned earlier, the idea of cumulative advantage and cumulative disadvantage that how you start out often cascades then over your trajectory through your life, so that you start out advantaged.  And that--that helps you each step along the way.  Or you just turn out disadvantaged and it accumulates the disadvantages.  Okay, so I'm going to get a little bit more into the Woodlawn Study.  Just to show some of these examples, this is a longitudinal study by community in Chicago, Woodlawn.  It's one of the 76 communities in Chicago.  At the time that the study started 1966, it was the 5th poorest community in the Chicago area, but there was heterogeneity.  This was a time of high racial segregation, so there were very poor people in the community but there were also middle and upper-middle class people who own their own homes.  So there was diversity.  So this is sort of the life course line with when we assess people.  I just want to set the context for this cohort and one of the main points of my talk is that we should not ignore context.  So this is the context for this cohort of young people and there were 1,292.  They came from the--all the public--the 9 public and the 3 parochial schools in Chicago.  So they were born in 1960, the 1950s had been a time of migration from the south, largely from Mississippi and Arkansas-Louisiana to Chicago so that half of the mothers of this cohort were born in the south.  They were born in 1960, the civil rights movement was inactive in the 1960s.  They were in first grade in 1966-67.  The assassination of Martin Luther King took place in 1968.  Riots in Chicago, followed that although not on the south side where this group was.  In Woodlawn, there was a lot of gang activity.  So, you may have even heard of some of the gangs, the Blackstone Rangers, and the El Rukns.  So that was a context that when these kids were going to grammar school that their parents needed to worry about their safety on the streets.  They would have graduated from high school in 1978.  That was also the year of the highest marijuana use in the United States, as documented by Monitoring the Future.  So it was a cohort that grew up at the time of high drug use.  There was a high murder rate in Chicago in the 1980s.  1982, was an economic recession so when these people would have been then joining the labor force, there were very high rates of unemployment.  A good thing that happened to this cohort was the election of Harold Washington in Chicago as mayor.  He was an African-American and he was able to bring the city together.  He was very integrative and brought the diverse population of Chicago together.  Unfortunately, he died 2 years after being elected.  And then in 1986, HIV was recognized as a disease.  So this cohort grew into adulthood with that disease.  Welfare Reform happened in 1996 and then in 2008, Barack Obama was elected president.  I mentioned that because Barack Obama was from the south side of Chicago so this was like Harold Washington.  This was something that may have been positive for this cohort.  This is the sort of a conceptual framework for the Woodlawn study across the top--oops.
^M00:45:17
[ Pause ]
^M00:45:25
I am going--yeah, here we go.  Okay, so this is a life--what we call the life course social field construct across the top or stages of life.  Then the bars are social context where people live their lives.  The first bar is the family, the second bar is the classroom and school, the third bar is peer groups, the fourth bar is your own family, the fifth bar is work, and then the sixth bar is your child's family.  Now obviously, this is an ideal type, not everybody lives that kind of life but these are major social fields where we speculated that adaptation needs to take place.  So we had a very specific reason for focusing on first grade children and that was because it was a time of transition between the family and first grade.  So we were interested in how that period of adaptation occurred.  But then as we've followed people through the life course, we've been guided by these contexts in terms of ones that we need to assess.  Okay, so in first grade, we looked at--we were interested in whether what--how do we know that kids are adapting to school?  So we had lots of interviews with teachers and they gave us the ideas of what is necessary for kids to do well.  And they were pretty consistent.  So there was social contact, there was achievement obviously, maturation, being able to concentrate and focus, the attention that we've mentioned.  And also, being able to conduct themselves with regulation which we've gone on to call a classroom behavior.  We then interviewed teachers about each child in the classroom to assess this adaptation.  What I'm going to do today is look at some adult outcomes at age 32, or age 42.  This is depressant disorder, school attainment and economic status from self-report.  And first, I'm going to connect this to family adversities.  We did something a little different maybe here.  We did what's called the cluster analysis but we--instead of trying to figure out the impact of all of these things separately, we put them together.  So we clustered these things so that we have an individual kind of analysis rather than a variable-oriented cluster analysis.  But these are the variables that we used.  Here are the clusters that we came up with.  The first cluster which we didn't designate should be mother-father but turned out to be mother-father as you can see, had better income, fewer moves, less, more mother's education, older age at first birth, better mother's mental health and less household disorder.  So that was the first cluster.  The second cluster which were mainly mother-alone families, and you can see there the outstanding characteristics of that cluster is poverty.  And then the third cluster which did a little better than the second cluster but also was--the main thing there was that besides being a second adult in the family, not the father, but as second adult, most often a grandmother also had the characteristic of being younger at the age of first birth.  So this is a description of the clusters.  Okay, so if we look at first grade characteristics, there's a clear difference in which children adapted to first grade well.  So those children and mother alone did more poorly that the children in the cluster, the mother-father cluster.  The children in the mother-other did less well in terms of aggressive behavior and less well in terms of achievement.  So they start off showing associations with poverty and adversity.  So, this just sort of summarizes that slide.  Okay, if we look at some adult outcomes, we see that those children from the most adverse cluster were more likely to end up with MDD, major depressive disorder, as assessed by the CD.
^M00:50:07
And also more likely to end up with alcohol use disorder.  So this is over a 35-year period.  Because aggressive behavior has been shown in our studies and other studies to have a long-term impact, we broke this down by aggression also.  So we looked at kids who have no depression and kids who had--I mean, no aggression and kids who had aggression.  And then looked to see how the outcomes would look for that.  And we see that depressive disorder is still mainly related to adversity and not to depression.  Whereas alcohol use disorder is higher in the depressed kids from the mother alone family and the mother-other families.  So we're seeing their impact to both the early aggressive and the early adverse situation.  So again, this summarizes that slide so for depressive disorder, it seems to be at early adversity that matters for alcohol disorder.  It seems to be both the early aggressive behavior and the early adversity.  This slide looks at school drop out in poverty at age 32 and age 42.  And there, we see that for school dropout, aggressive behavior is what seems to matter later on.  For poverty, it seems to be early adversity and for poverty at age 32, for poverty age at 42, it seems to be the early aggressive behavior.  Now, you need to keep in mind in these results that the first cluster, the mother-father cluster had much less aggressive behavior to begin with.  So it's not exactly evening things out in that regard.  So I didn't show you the delinquency in crime data but that's summarized here so that the early aggressive behavior seems to have impact for these later adult outcomes.  So I want to highlight the importance of early aggressive behavior and early adversity here in terms of how kids do.  We've always thought of aggressive behavior as not being only individual characteristic but being an interaction between the environment and the child.  There's some evidence for this and a randomized prevention trial that was done based on the findings of the Woodlawn study where they targeted aggressive behavior in first grade by--kids were randomized, teachers were randomized and teachers then set out clear rules for behavior, rewarded kids in teams.  Now, there wasn't a team that won or a team that lost, each team could win.  But teams are rewarded not based on what individual kids did, but how the team did.  So there was peer pressure built in, for the kids to behave.  That had long-term impact as far as 19, in terms of school success.  Only for the aggressive children, not for the--it was called the universal program because it was in the whole classroom.  But the aggressive kids are the ones who benefited from that intervention.  So this was 19 schools and that's now been replicated in different countries and in different areas in the United States.  So what that prevention shows is not only that there are things that we can do but that aggressive behavior is a malleable behavior.  It's not something that's a characteristic of the kid.  It's something that can be changed.  I want to show a couple more slides from Woodlawn.  Incarceration is a problem in the community such as Woodlawn.  African-Americans are incarcerated at 6 times the rate of white males, 1/3 of African-American men spend time in jail.  Incarceration is more common than going to college or serving in the military.  What we focused on here is the disruption it causes for their families.  So we looked at the mothers of the incarcerated males in our population.  1/4 of the males were incarcerated.  They had--mothers of these males had significantly greater psychological distress and this is even when controlling on their earlier psychological well being and other adversities.  And as far as we could investigate, the mechanisms included the financial burden to the mother of her son's incarceration and the extra burden that she had in terms of caregiving for her grandchildren.  So we would expect they are to be stressed for those who are incarcerated but it turns out that there is also a lot of stress, that's engendered for the family of those who are incarcerated.  This is backing up what Lorah had said about the difficulties of foster care.  We did not have so many children in foster care in our population but their rate of mortality by age 42 was dramatically enhanced.  So you can see here that--oops, the dark blue is the mortality of the non-foster care population and the aqua is the color of the foster care kids.  You can see the extremely high rates of foster care, the high rates of mortality for foster care kids.  So it's 9 times that of the others, at least in the highest part.  Okay, so in thinking about stressors, the social and environmental context cannot be forgotten.  One in four children in the United States lives in poverty.  Poverty comes with many stresses that are often beyond the coping resources of even the most confident people.  Poverty not only brings stressors but it brings--it also impacts the coping resources that we think of to deal with stress in terms of social support, feelings of failure, feelings of control.  And then there's also the problem of the accumulation of adversities.  So, I hope that--I guess the message I want to bring from this is that, you know, when we think about stress, we need to think about the environmental part as well as what's inside of us.  Well, how's my time?  Okay, so I want to go on and just present a little bit of data from the--about social inequality and social inequality here, and its impact on life and what we might think of it with regard to stressors.  By social inequality, I'm referring to the distribution of resources across the society.  So are you in a society where everybody has relatively equal access to wealth?  Are you in a society where people on the top have a lot more than people on the bottom?  This is kind of what the recent movement of the 99 percent versus the one percent has been referring to.  But it's been a topic of study by epidemiologists for the last 20 or 30 years.  And it's generally measured by two ways of measuring.  By measuring the gap between, the income of the top 20 percent with the income of the bottom 20 percent or something called the Gini coefficient, which I'm not going to go into, but it--so, what the epidemiologists have found is that, if you look at more industrialized, richer societies, those societies with more income inequality have worse, have a number of worse outcomes, even if you're controlling on the average income within the society.  So let me--
^M00:58:47
[ Pause ]
^M00:58:51
This work that I'm sighting comes largely from Wilkinson who has been an investigator in this area for a long time, as well as forming a critique of that by Karen Rollinson.  So if you want to look at these things.  Okay, I don't know if you can see this but what this is, is health and social problems are worst in more unequal countries.  And these are countries, these are industrialized wealthier countries.  We see along the bottom here, income inequality and then we see on the vertical axis kind of a summary of health and social problems.  And you can see there, can you read what's included in the problem's life expectancy, math and literacy?  And then countries are arrayed according to their income inequality and their worst problems.  So as you know, the US was--oops, the US here is the top of both.  So we have the highest income inequality and we also have--we do the worst on these things.  
^M01:00:02
This is among industrialized countries.  At the bottom is Japan, Norway, Sweden.  Up there with us is Portugal and UK.  So this is looking at health and social problems by social inequality.  Can you see it?  Yeah, right.  New Zealand and Australia also have high rates so okay.  This is the US arrayed by social inequality of states and I know you can't see this, so let me sort of point out.  So states with low--with low social inequality are Utah, New Hampshire, Arkansas.  And they tend to have fewer--the fewer index is social problems.  Those states with high--New York has a very high index here.  What?  Income inequality, this is Mississippi, Louisiana, Alabama, Texas, so this is looking at the same index by social inequality.  Here, we have levels of trust and this was indexed by asking people within the countries.  How much can you trust other people?  And there is a reason why I'm showing this which I'll get to later.  But again, you see this general relationship that although the US is a little bit of an outlier here, we tend to trust people more than what maybe we would be expected to.  But in general, there is a relationship between feelings of trust in the society and social inequality.  This is the same data presented by US State and New Hampshire in Utah are they are the highest in terms of lowest social inequality and the highest trust, North Dakota.  Life expectancy is higher in the more equal societies.  So Japan has the highest life expectancies, Sweden, next.  US is down sort of toward the bottom, Portugal--
^M01:02:35
[ Pause ]
^M01:02:43
We've heard some about obesity and its relationship to stress.  We see here that, that also is related to the inequality in different societies.  This is school drop out in the United States by state.  Okay, so summarizing this, income inequality is correlated with many health and social problems.  Does this association cause health and social problems independent of other factors?  So that's the big question, people have been struggling with it.  Some of the answers or some of the mechanisms they give are one that's labeled status anxiety.  So this argument goes that one in a very unequal society, one feels anxious about one's status.  So that one is always trying to keep up.  So if the super rich build lavish houses then the merely rich build larger houses and the effect cascades down to the middle class.  So this results in a higher fraction of our incomes being spent on housing and with raised expectations of what is basic for us.  So this then means two-income families are necessary, long-working hours are necessary, so that's one explanation.  Another explanation is that when you have high levels of income inequality, lower levels of trust, there is less willingness to cooperate and support--there is less willingness by citizens to cooperate and support each other. So investments for the common good which are things like--common good would be clean water, fire stations, highways.  So how much is a society willing to invest in these things?  So I guess--I hope that the relevance for stress of all of these is that the societal context may need to be added to the list of stressors that we pay serious attention to.  Thanks.
^M01:04:55
[ Applause ]
^M01:05:04
>> Let's enjoy a 15 minute break for our refreshments.  Oh sorry, do we have time for questions?  Yeah, wonderful, let's take some questions then.  Yes?
>> Can you tell me [inaudible] they get this period level?
>> Yeah, and they've tried very hard to make this data very accessible.  So let's see if I can find the slide where that is.  It was just a slide with two references and, you know, you can download them in three seconds.  And they've tried to make this accessible to the lay as well as to those of us like me who needs sort of an accessibility issue so not that one.
^M01:05:55
[ Inaudible Remark ]
^M01:06:00
Yeah, really.
>> Can we--but what's the solution?  What are some things that you would recommend [inaudible] through justice?
>> Well, I mean I hate to get into political things.
>> Why?
>> Yesterday, the New York Times talked about that this inequality has gotten worse in the last year.  They cite one of the major causes is being the Bush tax cuts that have decreased the middle class, increased the poor and increased the super rich.  So we--I think when we talk about societal inequality, we really need to talk about policy and political things because those are the things that can influence how wealth is distributed.  So in terms of societal inequality, that's what I'd say.  In terms of data from Woodlawn, there is this very successful program that I described.  It's good for kids.  It's good for teachers.  It seems it's cheap.  It's being tried now in different places around the country.  So that's, you know an intermediate, it's called the good behavior game.  I don't mention it because it's a game which doesn't really mean what it is.  But it's--it--teachers then have very--make explicit to the kids what the requirement are for good behavior.  It's good for the teachers because the biggest reason for teachers to leave a school system is burn out from not being able to manage classes.  It's good for the kids.  It's not competitive.  Everybody can win.  It builds up a sense of camaraderie with your peers.
>> Thank you, yeah?  Could you say your name please?
>> My name is Sejal Patel; I'm a historian at the NIH.  I'm wondering, can you describe the--if you still a have working relationship with the Chicago Public School and the Chicago Department of Health?
>> We have an active Chicago Board for the study which is composed of citizens who right now, they don't have to live in Woodlawn because the population doesn't live in Woodlawn.  And there are people on that board that are very actively involved in the Chicago Schools or Chicago Political scene.  So it's not that I do through them but it's that resource.
>> Any other questions?  Carolyn?
>> In terms, I have two questions, in terms of the Woodlawn study, was there a difference in outcome between boys and girls?  And I guess my second question had to do--tell a different issue.  If you look cross-culturally, I gather the important issue is the difference between the top and the bottom, not the relative level of poverty, is that the case?
>> Right, and I didn't show the slides, but if you go to the website, they'll have the slides with the average income and it's just a, you know, random set of dots.  With regard to your first question, I usually always present gender differences 'cause there is a big difference.  Males are much more likely to be aggressive early on in first grade as we have heard yesterday.  They're much more likely to have died.  They are also less likely to have attended college, but they are less likely to be obese.
>> Any other questions?  Wonderful, thank you so much!
>> Yeah, thank you. [Applause]
^M01:10:03
>> So let's have our break, 15 minutes.  So I'm very happy you are here to explore placebo and placebo effects in human society, so I just learned what placebo meant.  Thank you, wonderful.
>> Thank you very much for this invitation.  Actually, probably, you know I'm not a stress researcher.  So what, that I'm here, actually, thanks to George, particularly to the organizing committee for inviting me and for giving me the opportunity to talk in this really beautiful context about placebo and nocebo responses.  So I think I've been invited here for at least two reasons.  The first is that the placebo response today is a very good model to understand how social stimuli, different social stimuli influence the patient's brain and actually can change the patient's brain.  So it's a very good model to understand how the psychosocial context around the patient, around the treatment, can influence the brain of the patient.  And the second reason, I think the second reason is that there are some similarities between a placebo response, at least as far as the neurobiological mechanisms of the placebo effect are concerned.  There are some similarities, of course, there are many differences as well between the placebo response, the stress response.  But I would like to show you particularly not so much for placebo response but for the nocebo response that there are some overlapping mechanisms between the stress response and the placebo response.  So I think these are two--the two main reasons why I was invited here.  I hope my talk will be useful in this context of a stress research.  So let me start with the just by showing you the overview of my talk.  You see that my talk is subdivided into at least the 5 parts.  The first one is about definition of the placebo response of the placebo effect.  We can call it either placebo response or placebo effect.  The definition is very important because there is a lot of confusion about these words, a placebo in the one hand and placebo effect on the other.  And the second part would be about pain, I would like to show you something about pain.  Actually, most of our knowledge about the neurobiological mechanism of the placebo effect comes from the filed of pain and analgesia.  And the third part would be about multi-performance, particularly about Parkinson's disease just to show you that pain is not a special case and there are some mechanisms and some social implications across a variety of medical conditions, not only on pain but other condition as well.  And the fourth part will be about the implications, some possible clinical and social implications about the placebo response.  So let's start with the very definition of the placebo response because the first question I would like to answer is, what are we studying exactly when we started the placebo effect?  So we can define placebo effect a context effect, the effect of the psychosocial context around the therapy, around the patient.  Just imagine a situation like this in which you'd give a medical treatment.  For example, you can give a pharmacological treat--a pharmacological agent, a drug.  If you give a pain killer, there are some specific effect of the painkiller.  If you give morphine, morphine bind to some receptors in the brain and the morphine inhibits the transmission of pain.  But when you give a pharmacological agent, actually, you give a drug within a very complex context.  For example, the site of the hospital of every professionals, of white coat, you know, that the smell of drugs is important as well, the words by doctors, nurses and in general, health professionals are very, very important.  And to be touched by complex machines like a probe of an ultrasound machine is also very important sensory stimuli--stimulus.  So all these sensory stimuli and I would call them socials, a sensory and social stimuli, tell the patient that a therapy is being performed.  So today, we are not so much interested in understanding the specific mechanism of a pharmacological agent, for example, of a painkiller.  What we want to understand, what is going on in the brain of these patients after a representation of all these sensory and social stimuli?  So what do we do?  We replace the real medical treatment with a dummy medical treatment, this is the placebo.  In this way, we have eliminated the specific effect of a pharmacological or non-pharmacological therapy.  And so, we can study what is going on in the brain of these patients following the presentation of all the sensory stimuli.  So in a single word, we can call this set of sensory stimuli and social stimuli the ritual of the therapeutic act. And the ritual of the therapeutic act I will show you that it's very important and it can change of the patient's brain.  So actually, there are many therapeutic ritual in our model and in non-modern medicine.  For example, the ritual of taking a pill, the ritual of a shot, the ritual of acupuncture which is pretty powerful, the ritual of surgery is really very powerful in inducing, that induce positive expectations in the patient.  Medical--the ritual of medical device like this one and the shamanic rituals sometimes are not very different from the rituals of modern medicine.  So in my talk, I would like to show you and I would say that the take home message is that all these sensory and social stimuli and all these therapeutic rituals can use the very same biochemical pathways which are used by the pharmacological agents we give in routine medical practice.  So for example, all these sensory stimuli and all these social stimuli can change the activity of opioid receptors in the patient's brain, cannabinoid receptors D2, D3, dopamine receptors and so forth.  So there is a sort of similar mechanism between the drugs we give in routine medical practice and the rituals we perform in routine medical practice.  A second point which is very important for the definition of placebo effect is that there is not a single placebo effect.  Actually, there are many placebo effects across a variety of medical conditions.  Unfortunately, I have no time to talk about all these medical conditions.  I will draw your attentions on at least two conditions, pain and Parkinson's disease particularly because we know pretty much about the neurobiological mechanism.  But you know, you see here that there are many, many conditions like for--and many systems like the endocrine system, like the immune system.  And in each and every condition, for example in anxiety or in depression, in pain, in Parkinson's disease, different mechanisms take place.  So there is not a single, actually, a single placebo response but there are many placebo responses.  So it is not correct to ask, what is the mechanism of a placebo response?  Actually, it is more correct to ask, what are the mechanisms of different placebo responses across different medical conditions?  So let's start with pain.  You will see that there are some interesting mechanism which are more or less related to stress that are not so much for placebo response but for the nocebo response, particularly.  So I would like to start by showing you a patient.  This woman is a very good placebo responder.  Unfortunately, not all patients respond like this one.  This patient underwent thoracotomy for lung cancer.  You see, this is the surgical wound which is pretty painful.  So if you ask this patient to reach the extreme position, you see here, there is a limitation of the range of movement.  This is not surprising at all of course because the surgical wound is pretty painful.  So if we treat this woman with a placebo, what does it mean exactly?  We give her a sugar pill or we give her a glass of fresh water along with positive verbal suggestions because we tell the patient, inside the pill, there is a powerful painkiller.  But of course, it is not true.  So this is a very good placebo responder.  So you see that if you ask after placebo administration to reach the extreme position, there is a dramatic change in the range of movement.
^M01:20:03
We did nothing inject anything actually here.  We did nothing inject any drug, any pharmacological agent.  We just injected the words, verbal suggestions.  You can also modulate this--the pain, the postoperative pain into the opposite direction.  You can give the very same placebo, you can give these patients the very same sugar pill, but along with negative verbal suggestions.  So you tell these patients, inside the pill, there is a powerful hyperalgesia drug.  So you should expect an increase in pain.  This is what happens, you see, that there is a further limitation of the range of moment compared with the no treatment condition.  So you see, this is a kind of modulation by using verbal suggestions, by using words and not by using drugs, not by using pharmacological agents.  So the crucial question is, from a neurobiological point of view, for a neuroscientist, I'm a neuroscientist, so of course, I am interested in understanding what is going on in the brain of these patients?  Why is there any analgesic effect in this condition after placebo administration?  And why is there any hyperalgesic effect here in these patients after nocebo administration?  So actually, you can modulate pain into opposite directions if you give--you see here, according to different experimental models both in the clinical settings and in the laboratory setting there.  If you give a placebo, this is the baseline, there is a decrease in a decreasing pain.   This is a typical placebo analgesia or placebo analgesic response.  But if you give a nocebo, which means that you give negative verbal suggestions, you see, there is--from the baseline, there is an increase in pain intensity, what we call nocebo hyperalgesia or nocebo hyperalgesic response.  So it is possible to modulate into opposite directions.  So the placebo response, the placebo effect is a very, very good model to understand how different psychosocial stimuli can modulate pain intensity into opposite directions.  So today, we know that actually, a very complex network in the patient's brain is affected by either positive or negative verbal suggestions.  At least 3 systems, the blue one, the red one, and the green one are affected by this kind of verbal suggestions.  So for example, you see here that the placebo analgesic response is mediated by an activation of a neuronal network which uses either endogenous opioids here in blue dye or in the green and the cannabinoids, endogenous cannabinoids.  And nocebo hyperalgesic effect is mediated by CCK.  So let me start with, which is quite interesting, let me start with the placebo analgesic response.  So, the involvement of endogenous opioids and endogenous cannabinoids.  So this is an animation of the brain of responses in different patients.  These are quite complex analysis, a metaanalysis of different brain imaging studies.  And you can see that we can subdivide the placebo response into at least two phases, there's a first step and a second step.  The first step is placebo administration and when you give a placebo actually, you give positive verbal suggestions.  So this is what we call the expectation phase, the expectation step.  In this step, during this stage, the patient expects a therapeutic benefit.  So there is a sort of anticipation of the therapeutic benefit or the clinical improvement.  In this case, the reduction in pain.  And there is a second stage in which there is an inhibition of all those regions in the brain which process pain.  So this is the animation you see here, there is during a placebo administration an expectations phase, there is an activation of different regions in the brain both at subcortical level and the cortical level.  And during the pain stimulation, you see here in blue that this blue region represents the inhibition of different brain areas which process pain information.  So you see for example that here, deep in the brain, the anterior cingulate cortex and other regions are inhibited.  These regions are very important when we perceive pain.  And they are very much related to our perception of pain intensity, pain unpleasantness and so forth.  So how does this system work?  You see here that this system is made up of at least two neurotransmitters.  There is--the first neurotransmitter is represented by endogenous opioids which are morphine-like endogenous substances which are released by our brain during a placebo response.  And the second system is represented by cannabis-like substances or what we call endogenous or endo cannabinoids.  And these endogenous substances bind to some receptors which are present in our brain, the mu opioid receptors and the CB1 cannabinoid receptors.  So these two systems are responsible for the inhibition of different regions, of the activity of different regions which are involved in pain processing.  So it is very interesting that actually, it is possible to block a placebo response because you can use drugs.  You can use pharmacological agents and you can block these kinds of receptors, so you can also block these receptors with the cannabinoid receptors.  For example, there are at least two categories of drugs, one what we call mu-opioid antagonist and the second class of drugs, the CB1 cannabinoid antagonist.  So it is possible to block these receptors.  And if you block these receptors, actually, you can block a placebo analgesic response.  You can see what happens in the brain after the blockage of these two inhibitory systems.  For example, you see here in orange, these orange areas represent that there is a relapse of pain.  So there is an activation again of the different brain regions which are involved in pain processing.  This means that in this case, we have blockage to placebo analgesic response.  We have blocked placebo analgesia.  So this is for a placebo response.  In placebo response, you see that the difference such as stimuli and sensory stimuli can change the patient's brain.  It can activate at least two systems, the endogenous opioid system and the endogenous cannabinoid system.  What about the opposite situation?  So we can give the very the same, we can give the same placebo pill, a sugar pill, but along with the negative verbal suggestions.  And you see here that this is the opposite response.  You give a nocebo which means you give negative verbal suggestions and you can induce what we call nocebo hyperalgesia which is opposite, compared with the nocebo analgesia.  This is quite interesting from a social point of view because there are many situations in our environment which produce nocebo hyperalgesia, just let me show you one example, for example, cellphones.  Cellphones are quite interesting because there are several studies which describe what we call cellphone or mobile phone-induced headache or mobile phone-induced hyperalgesia or cellphone-induced pain, generalized pain usually in the head but also in the neck, you know, in different parts of the body.  Clearly, this is nocebo effect; these are phycological effects because electromagnetic waves have no effect on pain.  And so, I would like to show you what is going on in the subject's brain when these subjects are exposed to negative verbal suggestions.  This is the--an experimental situation just to show you how we run an experiment in the lab under strictly-controlled conditions.  And these are--this is not a patient.  These are healthy subjects as the volunteers and so this is the experimental model we used, you see?
^M01:30:00
We induced what we call experimental ischemic arm pain.  We inflate a cuff, a sphygmomanometer cuff and this is quite painful.  You can see that there is a kind of pain which increases over time.  And then, at the same time, we measure the hypothalamus, pituitary adrenal axis, you see that we measure ACTH.  This is an increase in the ACTH and of course, this is not surprising because the pain is a stressful condition and we also measure cortisol here, the level of the adrenal glands.  So you see, this is a typical response to what we call ischemic arm pain, experimental ischemic arm pain.  So now, we can increase these responses, so we can increase a pain, we can increase ACTH secretion and we can increase cortisol secretion by using the negative verbal suggestions.  If we give a nocebo pill, which means we give a placebo along with negative verbal suggestions.  We tell the subjects, "Now, your pain is going to increase in a few minutes."  You see that this is a typical nocebo hyperalgesic response.  This is a typical ACTH nocebo response.  And this is a typical cortisol nocebo response.  You see that this is very much related, they're very much related to stress research, particular the nocebo counterparts.  Not so much a placebo response but a nocebo response.  So here, you see, we have both subjective pain intensity and objective responses following nocebo administration.  It's quite interesting that all these responses are due to anticipatory anxiety because it is possible to block these responses, all these responses by giving diazepam.  So, this dose of diazepam is capable of blocking all these responses, both hyperalgesic responses and, or hormonal responses as well.  But if you give a CCK antagonist, in this case, we use the proglumide.  Proglumide uses non-specific CCK, CCK A and CCK B that are two kinds of receptors in the brain.  This is a non-specific CCK A, B receptor antagonist.  You can see that there is a very specific effect on the nocebo hyperalgesic response but not on the hormonal nocebo response.  So proglumide has no effect on ACTH and on cortisol but it has a powerful effect on the hyperalgesic nocebo response.  So this is the model we have today, two drugs with two different mechanism.  If you give, you see here, nocebo induced anticipatory anxiety and the anxiety activates at least two different pathways.  The first pathway is the activation of the hypothalamus, pituitary adrenal axis and the second pathway is a CCK, Cholecystokinergic pathways, linking the anxiety with pain.  Actually CCK has a facilitatory effect, facilitatory effect on pain transmission.  So, if you give diazepam, diazepam block anxiety, diazepam is a typical anti-anxiety drug.  So if you give diazepam, you block anxiety so you block everything, you block the activation of ACTH and cortisol but you also block the activation of CCK here.  But if you give proglumide, if you block--specifically, you block the CCK pathway, the CCK receptors; you can block only these pathways, the pathways linking anxiety to pain.  So, proglumide has no effect on the ACTH and cortisol response, it has a specific effect on the CCK pathways linking anxiety to pain.  So, in this case, CCK--the proglumide is not to a real pain killer, it's not a real analgesic drug.  It has a specific--it has quite a paradoxical effect, a strange effect because it has a specific effect on the pathway linking anxiety with pain.  So in conclusion, a negative--negative psychosocial context, this is very much related to stress, to stress research.  Negative psychosocial context can produce different changes in the patient's brain.  For example, it can induce an activation in the release of CCK, of cholecystokinin.  So this is the model we have today and the model we have today is quite interesting because there are at least three neurotransmitters.  On the one hand, you see here, the placebo suggestions, for example, the ritual of acupuncture which is pretty powerful in inducing positive expectations, activate both endogenous opioids and endogenous cannabinoids.  And on the other hand, nocebo verbal suggestions, just in the example of the cellphone-induced headache or cellphone-induced pain can activate a CCK system.  And activation--the activation of this CCK system has a facilitatory effect on pain transmission, so there's an increase in pain, the nocebo hyperalgesic effect.  Well, it is quite interesting that as I said before, it is quite interesting that it is possible to modulate this effect, this psychological effect from a pharmacological point of view.  Naloxone and rimonabant, naloxone is an opioid antagonist and rimonabant is a cannabinoid antagonist.  It is possible to block placebo suggestions by using these two molecules.  And it is possible to block nocebo suggestions by using this molecule, a CCK antagonist blocking both CCK A and CCK B receptors.  So, and what about motor performance?  Very quickly, just in a couple of minutes just to show you, I don't want to go into detail of the neurobiological mechanism but just to show you that pain is not a special case.  All these effect are present across a variety of medical conditions including motor disorders like Parkinson's disease.  Parkinson's disease is quite interesting from a neurobiological point of view because it is possible to study by using in vivo receptor binding.  It is possible to study the release of dopamine in the brain of Parkinson patient and it is also possible to recall from single neurons during the implantation of electrodes for deep brain stimulation of Parkinson's disease.  Just let me show you a couple of slides about what we know today, about the neurobiological mechanism of the placebo response in Parkinson's disease.  And in this case of course, verbal suggestions are not about pain but about motor performance.  Parkinson's disease is a motor disorder.  So usually, when we give a placebo to our Parkinson patients, we tell the patients that, "Now, your motor performance is going to improve."  This is a PET study which uses a raclopride.  For those of you who are not familiar with raclopride technique, I'll just tell you that when you give raclopride, raclopride is--it competes with endogenous dopamine for D2, D3 dopamine receptors.  So if there is a decrease in raclopride binding, this means that there is a release of endogenous dopamine and this is what happens.  You'll see that this is just before placebo administration.  This is right after placebo administration.  You'll see here the red spots.  This is the left striatum.  This is the right striatum which is affected in Parkinson's disease.  And you see that after placebo administration, there is a dramatic decrease in raclopride binding which means that there is a powerful, I mean, there is a release of endogenous dopamine.  Just to give you an idea of the amount of dopamine which is released, following positive verbal suggestions, I'll remind you that we did not give any drug.  But after verbal suggestions, there is an increase in extracellular dopamine of about 200 percent which is really a huge release, which more or less corresponds to a full dose of amphetamine.  Unfortunately, these effects last very--are short-lasting and sometimes are unpredictable.  So, we cannot predict in advance who will respond to placebo, who will not? 
^M01:40:00
So this release of dopamine, of course, this is not surprising, it has a powerful effect on the activity on the neuronal activity of different neurons of different regions in the basal ganglia which are very important in Parkinson's disease and in general, in the motor performance.  So it is possible to recall, it is possible to recall from single neurons during the implantation of electrons for the deep brain stimulation which is a pretty effective treatment for Parkinson's disease for those patients who no longer respond to pharmacological agents antiparkinson pharmacological agent.  So in this case you see, this is the electrode tip, this is an implantation of the electrodes, this is the electrode track.  The electrode tip is in the subthalamic region so we can record from single neurons.  I don't want to go into details here but I will like to show you that positive verbal suggestions can change the activity of single neurons.  For example you see here, this is just before placebo administration, this is the baseline condition, this is the control condition and you see that this is a pathological activity.  There is a very high firing rate of this neuron which is inside the subthalamic nucleus which is the major target for deep brain stimulation in Parkinson's disease.  And so down, we give a placebo which means we give a subcutaneous injection of a saline solution and of course, saline solution is not a powerful antiparkinson agent.  It has nothing to do with the improvement of motor performance.  And when we perform a subcutaneous injection of saline solution along with positive verbal suggestions, we tell the patients, "Now, your motor performance is going to improve."  And you see that there is a dramatic decrease, it is not necessary to describe the decrease here, you see the dramatic change in activity of the neurons in the subthalamic nucleus.  So this verbal suggestion can really change the patient's brain at different levels at the level of single neurons as well.  So, motor performance is also physical performance, just 30 seconds, a 30 or 40 seconds about physical performance because we are working a lot about physical performance.  And I just tell you, within this context, I just tell you that placebo can also boost physical performance in sports and in particular situations like in extreme environments.  So you replace a symptom like pain, like motor performance in Parkinson's disease with a physical performance in sports and in extreme environments.  And also, nocebos which means negative verbal suggestions can prevent good performance.  So, we find the very same effect in the clinical setting and in the physical performance setting, this is quite important and many people are working a lot not only in the clinical setting but in the setting in extreme environments.  For example, we have a beautiful university facility which is at the border of the Italian Swiss Alps and we work, and we work at an altitude of more or less 4,000 meters to understand what happens to--I mean, not so much what happens, how to increase performance, for example, in this unusual situation.  So implications, actually, there are many implications.  This is of course is the last part of my talk.  There are many, many implications but I would like to draw your attention on a single clinical implication which is quite interesting from a pharmacological point of view, from a psychological point of view and I hope we can stimulate some research in the field of stress as well.  And it is quite interesting because this is the model which is emerging today in placebo research, in the clinical setting.  You see that this is quite an interesting model because you see that the ritual of the therapeutic act in the psychosocial context around the therapy can activate some molecules in the brain.  For example, we have seen opioids, cannabinoids, CCK, you know?  So, there is an activation of these molecules and these molecules bind to the very same receptors, to which drugs, we give a routine medical practice, binds.  So, you see for example that the narcotics bind to mu opiate receptors but expectations about the narcotics activated the very same mu receptors.  A negative expectation can't activate CCK but a drug-like CCK use the very same receptorial--by chemical pathway.  So, when we give a drug, for example, when we give a painkiller, when we give a pharmacological agent like morphine, morphine binds to more opioid receptors but expectations about the morphine activates the very same receptors.  So, I mean, the reason an interference between a social stimuli and the drugs we give in routine medical practice.  So the crucial question I would like to ask you now is what happens if we eliminate the psychosocial context, what happens if we eliminate expectations?  So is there--I men, the crucial question is--the key question is, is the action of morphine for example, is the action of a painkiller the very same without expectations, without these importance psychological component.  So, just imagine a situation like this.  This is a routine medical practice, a routine medical practice, this doctor is giving a painkiller, and there is a very complex psychosocial context around the patient, some intravenous lines, some complex machines, some computers, you know, some syringes, these are the context, the usual context in routine medical practice.  And the doctor herself here is a powerful component of the psychosocial context, of course.  And the--so the question is what happens if we give the very same drug at the very same dose with the same infusion rate--I mean nothing changes, but we give the drug in this condition?  So the crucial point here that these patients do not know that any drug is being given, what we call a hidden administration of the drug.  So this patient does not have any expectation about clinical improvements.  Is the action of the drug the same or something changes?  I would like to show you from a clinical point of view--well, actually, this is a very long story, just to make the long story short.  In the couple of minutes, I would like to show you the comparison of four painkillers in this two conditions, these are what we call open injection or if you prefer, an expected injection according to routine medical practice.  And this is what we call a hidden injection or an unexpected injection because in this case, the very same drug and the very same dose with the same infusion of rate and nothing changes is a given by a computer machine.  So the crucial point here is that the patients do not know that any drug is being given.  So here, you will see decrease in pain, the pain reduction and you see this is what happens for buprenorphine in open injection is more effective than a hidden injection and this is true for other painkillers as well.  You see that this is true for tramadol, ketorolac and metamizole 1:48:38 in all these situations, hidden injection is less effective than an open one.  So particularly here for metamizole or for ketorolac, you see that the hidden injection is almost ineffective in reducing pain.  So from a pharmacological, but I would say from a psychological point of view, this is quite interesting because we can separate the real pharmacodynamic effect or the psychological effect.  In this case for example, for metamizole, you see that the real pharmacodynamic effect, the real specific effect of metamizole comes from the hidden injection, because the hidden injection is free of any psychological contamination and I don't use the word contamination with the negative meaning, of course.  The rest is a psychological effect, so you can see that it is possible to study and it is possible to identify a placebo response, a placebo effect actually without giving any placebo.  Let me show you, this is one--it should be one or two last slides but it is quite interesting to see the progression, the time course of the clinical trial and how we run a clinical trial like this with the hidden administration and open administration.
^M01:50:05
So these are classical--this is the clinical trial which tries to answer the question: is metamizole at this dose effective in post thymectomy pain?  So according to classical clinical trial methodology, you know, classical clinical trial methodology uses two groups of patients, one groups receives the real treatment and the second group receives a placebo, this is classical clinical trial methodology.  But in this design, both groups receive metamizole, both groups receive the active treatment but the first group receives an open injection of metamizole according to routine clinical practice, the second group receives a hidden injection of metamizole which is performed by computer.  There is a full informed consent by these patients because this is what we tell the patients, "You will receive metamizole."  But actually, you don't know when the computer is going to deliver metamizole.  It could be, you know, it could be after 1 hour or after 1 hour and a half or after 2 hours, nobody knows.  This is performing according to double-blind party.  And this is the time cause--this is an animation which is more impressive of the clinical trial and these are the two groups of patients you see, this is the open group or expected injection of a metamizole; this is the hidden group, unexpected injection of metamizole.  Again, in this group, the injection is performed by computer and here, the patients do not know and the patients--neither the patient know that the experimenters know when the computer is going to deliver metamizole.  So, the duration of this trial is more or less 6 to 7 hours.  Here, you will see the progression of pain intensity.  We start--you see from a pain intensity of about 5 and here, you see--this is the timing of a metamizole administration and right after metamizole administration, there is a decrease in pain intensity.  Here, there is a decrease then there is relapse of pain.  Of course, here, nobody knows when the computer is going to deliver metamizole, it could here, it could be here, it could here so you see that there is a significant difference between these two groups here, we have an analgesic effect here, we have no analgesic effect.  So, the very end of the trial, of course, we ask to the computer, "When did you deliver metamizole in this group?"  And this is the answer, "In this case, metamizole was delivered here and you see that there is no effect of metamizole in this condition at this dose in this, of course, in these conditions in post thymectomy pain."  What does this means?  This means that this is not a pharmacodynamic effect of metamizole, this is a psychological effect otherwise, there should be no difference between an expected and unexpected injection of metamizole.  So there is no pharmacodynamic effect of metamizole, this is a psychological effect or if prefer, this is a placebo effect.  So, you can see it is possible to identify with the study placebo effect without giving any placebo.  So, at the very end of my talk, you see that this is again the model which is emerging today.  There is an interference between a social stimuli and the drugs we give in routine medical practice.  There are different therapeutic rituals, this is just, for example, just as an example acupuncture and the ritual of a taking your pill, and unfortunately, I didn't have enough time to talk about other medical conditions as well, but you see that this is a very general phenomenon.  It is true in the immune system, it is true in the cardiovascular system in which there is an activation by social stimuli, there is an activation of the beta-adrenergic systems, and--but the general model which is emerging is that the reason interference between social stimuli and the drugs begin with routine medical practice which means basically that different emotional, cognitive, affective factors, psychological factors, and in general, the psychological state of the patients can change the action of drugs because the psychological state of the subject of the patient's use of the very same biochemical pathways which are used by drugs.  So, you can see sometimes, it is very difficult from a pharmacological point of view and from a clinical point of view to say whether or not a drug is really effective.  So, I would like to conclude with the very provocative sentence and to take on message not from me but it is from Voltaire and he said, "Doctors pour drugs of which they know little, to cure diseases of which they know less, into human beings of whom they know nothing."  Thank you very much.
^M01:55:35
[ Applause ]
^M01:55:42
>> So please, any questions?  Philip?
^M01:55:47
[ Inaudible Discussion ]
^M01:55:51
Is there a mic for Philip?
>> Thank you so much.  That was incredibly inspiring and there's so many questions, fantastic research, that's exemplary.  Thank you very much to you and your whole team.  One question is you clearly showed the psychological effect for the--that interacts with the actual pharmacological effect, the additive effect.  But I was also wondering if you've don't studies where you hone in on the message that the physician and or the whole social context is doing to amplify the additive effect of the psychosocial so that there's--for example, you can also say, can the physicians say, "I'm going to give you this morphine, you're really going to get morphine but you know what?  It's not going to work."  And so you have the red bar which is the reduction in pain which is the actual pharmacological effect but can you reduce that effect by a negative message even when the morphine is given?  That's one.
>> Unfortunately, I don't have an answer because we don't know yet.
>> Okay.
>> That's very important point because I will say that one of the future challenge of placebo researcher and pharmacological researcher and neuroscience research in general is that you need to better understand whether the psychological I mean, expectation for example, where the expectation on morphine use the very same receptor simultaneously I mean, or as you say the reason additive effect.  I give morphine without expectation and morphine binds to some mu opioid receptors then I give morphine in full view of the patients.  The patient expects something, expects the therapeutic benefit and in that case, you have a sort of amplifying effect and so I have a recruitment of some more and more opioid receptors, you know?  This is what we call an additive effect.  Otherwise, instead of an additive effect, it is possible that--I don't think this is the case but it is possible that the expectation effect and the drug effect you use simultaneous is the very same receptor which means that they compete for the very same receptors.  I believe my opinion, my opinion is that there is an additive effect, both expectations and narcotics use mu opioid receptors but when you give morphine, there is a recruitment of 50 percent of the mu opioid receptors.  When you give expectation, another other 50 percent is recruited, you know.  That's the very important point.  From a pharmacological point of view, it's quite complex but it's future challenge for research for sure.
>> Research possibility is a measuring the trust that the patient has for the physician.  The higher the level of trust and when you walk in the room and say, "Philip, you are going to get morphine and this is really going to work.  Pharmacological effect should be the same but the additional psychological effect should be even bigger if my expectancy and the trust of the message that you're giving me.  I'm thinking about this in multiple context but that's might be--I'm trying to think of other specific psychological factors that are mechanisms for this psychosocial effect and when I think of the shamans, or, you know, any kind of thing like that is there's a certain--there's a really incredible belief in that person's role, social role and the expectation that they hear, she will heal me, so it's very--yeah.
>> Yeah.  Unfortunately, we don't know very much about trust but we know pretty lot of the expectations.
^M02:00:07
I don't know whether or not they are the same thing, I mean, we could discuss about that.  We know pretty lot about the expectations, you can increase.  You said that you can increase trust, but actually you can increase expectations.  And just to give you an example, there are two different methodological approach in a clinical trial on when you give a placebo.  You can use the double-blind paradigm and in a double-blind paradigm actually, what you tell the patient is that you have a 50 percent chance of receiving either a placebo or the active treatment.  So, this leads to uncertain expectations, but there is a second way to give a placebo, you give the placebo but you tell the patients this is a powerful painkiller which means that you have a 100 percent chance of getting the real treatment.  This of course, is related to certain expectations, it makes a big difference.  The effects--I mean, the magnitude of the placebo effect is much larger, not so much in the double-blind but in the deceptive administration procedure.
>> This is so true because I actually have been working on a paper that is social pain, you're about--with your [inaudible] on, you are about to get criticized or nothing or praised.  But there's 4 and a half seconds before where you don't know what's coming, uncertainty, totally activates fMRI pain matrix.  I mean, a context of uncertainty about what's going to be delivered socially.  So, not even physical pain, it activates the pain matrix in the brain.  [Inaudible] Thank you so much.
>> I know there are many questions.  I think we have time for one more.
>> Maybe two.
>> Two more.
>> Yeah, thank you.
>> I know that some of the people are sensitive to placebo because there are some people who don't respond at all to placebo and is that genetically and epigenetically defined?
>> Yeah, that's an important point and of course, I didn't have time to talk about to t the problem of placebo responsiveness, why some people respond to placebo, why some other people do not.  There are at least two explanations, the first is that basically--very often, I mean, the placebo response is a learning phenomenon.  It's a learning phenomena because if you give a placebo for the first time, sometimes there is a response, sometimes the response is significant, some other times, it's not significant.  You know, it is at the borderline between significant--from a statistical point of view.  But if you give a placebo after repeated administration of effective treatments, for example, if you give morphine on Monday and you give morphine on Tuesday and again morphine on Wednesday and again morphine on Thursday but on Friday you replace morphine with a placebo, you can better virtually old patients, more or less 100 percent of the patients will response to the placebo.  So these are learning phenomenon.  So, some people do not respond to a placebo probably because they have not learned it yet.  The second explanation is genetics.  Unfortunately, we know very little about the genetics of placebo responsiveness, we know something about social anxiety and depression.  There are a couple of studies and so we have to be very careful and we have to be very cautious to consider this genetic data but, there are some genetic bias which respond pretty well to placebos and some genetic bias whether or not to respond and they respond poorly to the placebo treatments.
>> Dr. Spiegel.
>> We'll talk--it reminds me of George Bernard Shaw's quote that a miracle is an event that creates faith, and that what your doing.  But in relation to your learning paradigm, Bob Ader, the late Bob Ader who proved that there is conditioned immunosuppression, raised a very interesting question that perhaps where our home notion of how we used our medications is wrong, that is overtime people should be condition physiologically to the response of the medications and you could probably actually get the same pharmacologic--the same effect with a reduced those and therefore fewer side effects.  If overtime as people became conditioned to the use of the medication, they're expectancy improved based on just their own experience with the medication.  So, if you have any comments about how we use medication in general given that there is this conditioning related to the placebo effect.
>> At conditioning--yeah, there is a very important point both from basic research perspective and the clinical applications as well.  There are many mechanism of conditioning, but when we talk about conditioning, I said, probably in my second of first slide, I said that there is not a single placebo response but actually there are many placebo--many placebo responses.  Sometimes, expectation is more important than classical condition and you mentioned Bob Ader.  Some other times, a classical condition is more important than expectations.  For example, with conditioning, with the classical conditioning, what we call Pavlovian conditioning, you don't need--to use a placebo response, you don't need to trust your doctor, you don't need to believe in the therapy because everything is unconscious.  Pavlovian condition is completely unconscious, so if you want to use a classical condition in procedure in clinical practice, you don't need the patient to be conscious because you need to give pharmacological agent many times, for example, you can give morphine or you can give--this works very well in the immune system in the endocrine system, and if you give an immunosuppressor for example, many times Monday, Tuesday, Wednesday and then your replace the immunosuppressor with a placebo you have a completely unconscious response.  So, from a clinical point of view as you say, from a clinical point of view, I would say that many laps all over the world, I'm trying to exploit this conditioning mechanism in order to reduce the intake of drugs, particularly of toxic drugs.  It is not very easy in psychiatry because the latency of anti-depressants, for example, is very long, you know, if you give an anti-depressant the latency is a couple of weeks even more than a couple of weeks.  So, this is feasible with painkillers with immunosuppressor where the latency is very, very short.  So, in that case, many times in our experience, for example, with Parkinson patients, if we give an antiparkinson agent many times and then we give a placebo, we can induce the very same response.  Unfortunately, there is an extinction phenomenon, so you need the reinforcement.  You cannot go on giving placebos, I mean, but you need it to reinforce by reintroducing into therapy the real drug.  That's a very interesting point, I would say, from a clinical point of view.  We are trying to exploit this mechanism in routine clinical practice.  Yeah.
>> And Norman.
>> Yeah.
>> And then--
^M02:08:10
[ Inaudible Remark ]
^M02:08:15
>> I would just like to echo those who've said the work is really elegant and impressive.  As a clinical psychiatrist who's preaching in a people all the time, many of whom have depression and other conditions that you haven't specifically covered here, I would still say that the work that you've shown can very easily be applied to a clinical practice, because I think that, you know, especially with depressed or anxious people, they have almost, by definition, negative expectations of everything including the drug you might be giving them including everything and to say, you know, we don't know it could be right, it could be wrong, but if we do take a positive attitude towards it, we may very well amplify the effect of the drug.  So, what's to be lost by hoping for the best?  Here's some wonderful data, it's in the pain area or the Parkinson area, but these are just the other brain functions and I wouldn't wait until you've done your studies with depression, with their two week latency and stuff.  I would say, you know, chances are different aspects of the brain could work in a similar way and we know placebo is powerful and I think that, you know, medicine should be given in the most positive way.  And then if they don't work, you know that all your placebo effects, there are nothing and you can change you medicine but I think that the data as presented give a lot of leverage to psychiatrists dealing with a variety of conditions other than those that you've described here, thanks.
>> Thank you so much.  Thank you very much Dr. Benedetti.
[Applause]
>> What?
>> Wait, you have one more, Dr. Benedetti.  Just--
^M02:10:09
[ Inaudible Remark ]
^M02:10:17
>> Is there any evidence or any [inaudible] self-administration of placebo, that is to say--oh, I wasn't on [inaudible].  I was asking about self-administration of placebo and I was going to say for instance, people who were deep meditators, who know how to bring attention to a certain amount of mind control.  Is there a possibility or a likelihood or any evidence or is anyone looking at whether through that mind control, you can decrease some of the negative effects of whether it's pain or whatever.
>> I would say, no.  It's not possible to--I mean, to devise a sort of--can I call it placebo self-administration as you said, because a placebo response, by definition--I mean, by definition, a placebo response needs a social conduct.  And this is very interesting from an evolutionary point of view because in my--actually, I talked about this issue in my latest book, The Patient's Brain: The neuroscience of the doctor-patient relationship.  The first two chapters are about evolution of placebo response of the doctor-patient relationship.  So you know that to induce huge placebo responses, you need a very good social contact.  So I agree that some other situations like, you know, expectations coming from within faith, religious faith can be a very important, but we know very, very little.  By definition, I would say that the social contact and different social stimuli are really the crucial point to induce placebo response.
>> I think probably Dr. Schneider is going to address some of these questions so I suggest we make that transition now.  Thank you so much, Dr. Benedetti.
[Applause]
>> Good morning.  Today, I'd like to talk about the neurocardiology of stress in resilience using meditation as an example and its effects on heart disease of resilience.  We heard yesterday from Dr. Chrousos and Dr. Gold about the effects of stress on cardiovascular disease and today, I'd like to go on to that level in a little bit more detail in terms of physiology and biochemistry and cell biology and then talk about some ways that that might be intervened upon.  The first, why cardiovascular disease and why is it important?  Well, according to the World Health Organization's recent review of global causes of death, this was the United Nation's conference about three months ago.  Cardiovascular disease is now the number one cause of death world wide.  It has been the number one cause of death in developed nations for many decades but now, even developing nations are suffering from this modern epidemic.  And that's from heart attack and stroke equal approximately all other causes combined on average.  What about the causes of cardiovascular disease and why is it increasing worldwide today.  These are data from the INTERHEART Study which is an international study that took place in 40 countries with 50,000 patients with coronary heart disease and looking at risk factors and as you can see, the conventional risk factors are there, smoking, diabetes, hypertension, obesity.  Apo B, ApoA1 is another way of looking at cholesterol and lipids and psychosocial stress has come out internationally as a risk factor for coronary heart disease which is equivalent to or greater than conventional risk factors like hypertension, obesity, and cholesterol.  This is a study on health care utilization looking at behavioral risk factors and tobacco use, exercise, body weight are all risk factors for a variety of chronic diseases that result in Medicare utilization.  And here, we have stress as measured by psychosocial instruments and depression as we heard about yesterday, our major risk factors which exceed more conventional behavioral risk factors for their effects on health care utilization and health care cost.  So we've got an issue here and of course, we'll been hearing about some of the neurobiological mechanisms just now in this conference on how psychosocial factors could influence biology.  Now, looking specifically at cardiovascular disease, it's been found that the psychosocial stress can be thought of in terms of stressors which you've heard about, the stress response which is either psychological response or physiological response and then there are moderators which we'll talk about today specifically such as coping but also social is important even socioeconomic status might be considered a moderating influence.  The physiological mechanisms in general, we've heard a lot about over this conference, the general neural mechanisms includes sympathetic tone, oxidative stress, neurohormones.  We've heard about inflammation and coagulation factors and withdrawal of parasympathetic tone.  Now, those general factors influence the vascular system quite specifically in terms of the cardiovascular system, blood pressure is raised acutely and chronically with activation of these systems even cholesterol is sensitive to cortisol levels and other stress hormones and then their health behaviors which maybe indirect mechanisms by which the stress-related factors affect disease.  More directly, activation of these neurophysiological factors damage endothelium.  It's been shown that animals in cages, for example, monkeys in cages subjected to social stress have higher levels of early atherosclerosis and they can be blocked by beta blockers blocking the sympathetic nervous system.  Endothelial dysfunction is a precursor to atherosclerotic plaque which has several stages in its development and these factors cause ischemia which is decreased blood flow to the heart and related to silent ischemia or painful ischemia.  And then atherosclerosis and ischemia and often blood clotting or thrombosis lead to acute coronary events, heart attack, and eventually death, so each of these stages has been related experimentally in laboratory animals and in many cases in humans to psychosocial factors and particularly psychosocial stressful factors.  So how can we intervene in this cascade of stress and cardiovascular disease?  I'd like to give you an example today of meditation or as we've heard before, deep mediation, in this case Transcendental Meditation, a particular technique that I'll describe that has a fair amount of experimental evidence.  And the theme of today is healing from within, how this experience might help the prevention and treatment of cardiovascular disease.  These are some people practicing this technique.  It's a technique that's practiced for 15 or 20 minutes twice a day, sitting comfortably with the eyes closed and no special position or location.  And during the technique, what people describe is that the active thinking level of the mind becomes more quiet.  One uses a sound which has a traditional name called mantra but it means a sound who's effects are known in a particularly effortless way without focusing on the intention and without open monitoring of the attention either.  It's a technique that actually allows one to experience quieter and quieter levels of the thinking process in an effortless way until one experiences a silent inner state of awareness called transcendental consciousness or transcendence.
^M02:20:04
Dr. Rosenthal will talk more about that in a book that he'll--of that title.  But basically, the word transcendence here means to go beyond, probably has a Greek root I would imagine, possibly.  And the idea here is to go beyond the thinking process to a state of no thinking.  So it's not observing, it's not being mindful, it's not focusing.  It's just a state of restfulness while being awake inside, also called restful alertness.  That state has physiological correlates that I'll go into now, and cardiovascular effects.  This is a physiological correlate at the state of restful alertness or transcendental consciousness.  This is a work done at UC Irvine a couple of decades ago, but it's a classic study that's been replicated several times.  These are cortisol changes in people meditating in the laboratory.  These are controls sitting quietly in perhaps the default network state.  They're just sitting not doing anything with their eyes closed, and these are people who have been practicing transcendental meditation for a couple of years and here they're meditating and here they have their eyes open.  And the middle line shows the controls who are restudied after learning transcendental meditation, and they had a reduction in cortisol during the practice that remains afterwards.  Several other neurohormones have been measured and other neuromodulators.  Serotonin has been shown to change increase with the transcendental meditation practice, there are changes in catecholamines, there are changes in beta-adrenergic receptors, down regulation chronically changes in dopamine activity also.  But because this talk is mainly about clinical disease states, I won't go into too much detail about the more basic science changes.  But I can't help but show you some brain imaging studies because we've talked a lot about brain imaging today in this conference.  This is work done by Andrew Newberg at the University of Pennsylvania.  He is well-known according to Time Magazine for discovering God in the brain, for measuring the--
[Laughter]
And here is an example of that.  These are people--he has measured a variety of practices in the laboratory and these are some of his subjects practicing transcendental meditation and the positron emission tomography changes are several increase in blood flow in the frontal cortex suggesting activation of higher brain centers and overall integration.  There is a decrease in blood flow in the thalamus area, sensory-motor area suggesting reduction and sensory-motor related brain activity, and a decrease in blood flow to the putamen also related to motor activity suggesting withdrawal also in motor activity.  There are also functional magnetic resonance imaging studies which is this slide.  I think I dropped from here.  Let me just go backwards a minute here.  Well, it did get dropped but anyway, Dr. Z.H. Cho at the University of California, Irvine did an elegant study which is not shown in this slide.  It actually was a pain study so very related to our last presentation.  And in that study, people were subjected to a painful stimulus weather in the fMRI in this case thermal stimulus and then before and after learning meditation for--and after 8 weeks later and there were reductions in response in the brain to the painful stimulus and centers the brain having to do with stress including the amygdala and other stress areas.  So how does this relate to clinical medicine?  We've heard a lot about blood pressure and its relationship to stress.  So here are some effects of this stress reduction modality on blood pressure.  This was a meta-analysis done at the University of Kentucky by Jim Anderson who independently reviewed the literature which yielded 10 randomized controlled trials on transcendental meditation and blood pressure.  And the results of that meta-analysis showed significant reductions in both systolic and diastolic blood pressure about 5 millimeters systolic and about three millimeters diastolic blood pressure.  These changes were compared to controls in many case placebo controls.  I should have mentioned that in the context of this morning's talk.  And also are similar to some treatments used in the first stages of hypertension, for example, diuretics often have effects on this order of magnitude.  This is another meta-analysis comparing or looking at all the published literature on mind-body interventions for their effects on blood pressure.  This systematic review in meta-analysis looked at all the high-quality studies.  In this case, studies need to be randomized controlled trials.  They needed to have active controls 'cause now we know that inactive controls may still not control for the placebo effect.  I'm not sure if they controlled for the nocebo effect, but in any case the placebo effect.  And they had to have had at least one replication.  So, when you look at the studies of mind-body interventions which meet those high-quality requirements for experimental design, there are 17 of them, the published literature as of 2007.  And as you can see this--sorry, the study is on progressive muscle relaxation showed no significant effect in those well-controlled studies on blood pressure.  The studies on simple biofeedback who meet those criteria showed no significant effect.  The studies on relaxation assisted biofeedback shows slight increases in blood pressure although that's not significant.  And the combinations of stress management plus relaxation also showed no significant effect.  Of course there are case reports, there are uncontrolled studies, there are observational studies which showed different results but these are the high-quality studies.  And when you look at the studies on transcendental meditation which meet the same criteria, there are continued to be significant effects in reducing both systolic and diastolic blood pressure.  This is work done out in the West Oakland Health Center in California, published in the American Journal of Hypertension.  This is a one year randomized controlled trial in hypertensive individuals.  The blood pressure results were published but I want to show you the changes in anti-hypertensive medication.  In this case, these are changes in medication over the one year of the trial in people randomized, to transcendental meditation, people randomized to progressive muscle relaxation which was matched for non-specific factors.  The muscle relaxation group was matched for instructional time, matched for home practice time, matched for expectation, and matched for enthusiasm and general qualifications and instructor.  And then the third group was a health education group who received education in conventional lifestyle modification for blood pressure, like exercise more and lose weight and avoid salt.  And when you look at the medication requirements for blood pressure over year's time, there was a significant difference between the transcendental mediation group and the other two groups in their meditation--medication requirements on top of reductions in blood pressure.  So the productions of blood pressure and reductions in blood pressure medications during that trial suggesting that the blood pressure reduction was conservatively estimated.  There's been a fair amount of work on stress-reactivity in these groups.  These are series of studies done at the Medical College of Georgia by Vernon Barnes and collaborators.  And in these studies, subject is in the Department of Pediatrics, so these were adolescent subjects with high blood pressure for their age, subjected in this case to a car driving stress.  I suppose for adolescents driving a car at least in laboratory is stressful, maybe for adults, it is too.  And their blood pressure was measured before and after one semester, one high school semester of practicing transcendental meditation compared to a health education control for the same--which had the same amount of class time and expectancy.
^M02:30:05
And after one semester of meditating, there is a reduction in the blood pressure response to the car driving stress compared to an increase in the control group over the same period of time with the same stressor.  So this laboratory stress reactivity has been correlated with long term changes of blood pressure.  So this reduction in acute reactivity may have something to do with resetting the sympathetic nervous in these individuals which may contribute to their lower blood pressure chronically.  These are the fMRI studies.  I suppose we can mention it here because it has to do with stress reactivity.  This may be the neural basis of some of the cardiovascular changes that we saw a minute ago.  I describe to you the study already but this is a graphic response, these are various brain centers which lit up during the stressful stimuli before learning meditation, these are subjects after 5 months.  And you can see at least qualitatively, there is reduction in brain activation and once again, when you look at specific brain centers that reduce activation in response to stress included the amygdala in other stress-related centers.  Diabetes is also been related to chronic stress, diabetes is at least type 2 diabetes related to insulin resistance which is thought to be the basis of the metabolic syndrome or generally which is the clustering of prediabetic state hyperglycemia, high blood pressure, obesity, alterations in lipids, and alterations in inflammation of blood clotting.  This was a study done at the Cedar-Sinai Medical Center in Los Angeles with National Institutes of Health Funding published in the American Medical Associations Journal Archives Internal Medicine.  In this randomized control trial, patients at Cedar-Sinai Medical Center will randomize to either conventional health education for heart disease where they got instructions to exercise more or change their diets and then the control--no, the experimental group that randomize transcendental meditation same class time, same home practice time.  And there were changes in insulin resistance relatively between the group--two groups that were significant.  There was a reduction in insulin resistance which is good, you don't want to resist your own insulin, you want to be sensitive to it.  There are corresponding changes in blood pressure.  So this may be a change in the pathophysiological mechanism of metabolic syndrome in relate to other changes we saw in blood pressure.  And if continued overtime, it would substantially reduce the risk for atherosclerosis as well as diabetes.  This is work again from Medical College of Georgia with adolescents at risk for hypertension.  Looking at weight, body mass index is related to metabolic syndrome as we just mentioned, we just looked at insulin resistance which may have something to do with weight and overweight.  These investigators look at body mass index again over one semester of time in individuals who practice transcendental meditation in this case, in their classroom, 10 or 15 minutes during homeroom in the beginning of the day and 10 or 15 minutes as the last class of the day, compare it to controls, in this case adolescents in this age group tend to gain weight over a semester of time.  But there was a relative reduction or prevention of weight gain in the experimental group which may be related to changes in insulin resistance so that was not measured in these subjects.  This is work done at the State University of New York in Buffalo a number of years ago published in American Journal of Cardiology.  This was a trial where veterans in the VA hospital were inline for coronary artery bypass graph surgery.  At that time, there was a fairly long wait list in the Veterans Administration hospital for coronary surgery.  And they elected to participate while they're waiting for surgery in this non-pharmacologic trial of transcendental meditation or control.  And in the mean time, before and after the intervention, they run on the treadmill and their ischemic responses were monitored by EKG as well as exercise tolerance.  The transcendental meditation group had an increase in exercise duration compared to control, maximum workload, and had a delay of onset of EKG changes indicating ischemia or ST onset which was significantly different.  So, remember from the initial diagram of stress and heart disease, ischemia, myocardial ischemia has been well documented to relate to psychosocial stress.  And here's the example of mind-body intervention to reduce exercise, stress-induced ischemia.  This was a trial conducted at King-Drew Medical Center in Los Angeles, this is in South Central Los Angeles including the Watts community.  This was done in African-American subjects who were at high risk for cardiovascular disease, this work was sponsored by the National Heart, Lung, and Blood Institute published in America Heart Association's journal Stroke.  And in this trial subjects for randomized--continue their usual medical care in addition participated in conventional education, lifestyle modification, they learn all about exercise and weight reduction and dietary changes for heart disease.  The experimental group got transcendental meditation and the investigators measured the thickness of the carotid arteries, carotid intima-media thickness, the thickness of the wall shows changes in early atherosclerosis, and it correlate it with changes in the brain and the heart, it's probably the best noninvasive measure of atherosclerosis.  And as you can see here, there's a relative reduction in thickness of the arteries in the experimental group compared to the control group.  This is the first time that it was shown under experimentally controlled conditions that a mind-body intervention alone could regress atherosclerosis.  Previous studies have shown that lifestyle modification can regress atherosclerosis.  But those studies typically use intensive programs, often with multiple modality involving the dietary changes, very low lipid diets, intensive exercise programs along with mind-body intervention.  But here, we have the mind-body intervention alone regressing thickening of the arteries.  So, how would that effect long term clinical events because we want to look at clinical outcomes there, the bottom line?  This was a study published in the American Journal of Cardiology.  This was the pulled results of two randomized trials using meta-analytic statistical techniques.  One trial was done in Boston by Harvard investigators, randomly assigning older individuals to the transcendental meditation or other active controls including the mindfulness control used at that time and other behavioral controls.  The second study was study of hypertensive individuals in Oakland that I'd showed the blood pressure results earlier.  However, what we and our collaborators did is took this trials independently published and conducted and went back to the national death index records and look at their death rates over maximum of 20 years.  So this is--anyway, retrospective data on prospectively conducted trials, got that one?  And when you look at the mortality rates over 20 years, these are the control groups, these are transcendental meditation groups, there weren't significant different between the various behavioral that controls so we combined them for this illustration.  Overall, there was a 23 percent reduced risk for death from all causes in the individuals practicing transcendental meditation compared to various behavioral controls.  And in consideration of Dr. Spiegel and others interested in cancer research, this--we are primary interested in cardiovascular disease, these are all hypertensive or high blood pressure subjects, but we couldn't help looking at other causes of death.
^M02:40:14
And when you look at deaths from cancer, there's a 30 percent reduction in cancer mortality in the subjects who are not particularly at risk for cancer except for age.  At that time they began participation in the trial, you might notice that there's a particularly strong affect in the first 10 years which seem to have tapered off after--in the second 10 years, this could either be due to two reasons.  One, is that these people were around 60 when they started the study or older.  So there actually, there were not many subjects, subjects of high error rate in these last few years.  The alternative explanation is you have to die sometime.  But at least there was an increase in the average survival rate of more than 20 percent from meditating alone.  This is a brand new study that took 10 years to do.  This was conducted at the Medical College of Wisconsin where individuals with documented coronary heart disease that means they all had coronary angiography which showed significant stenosis in one or more of their arteries.  They all continued usual medical care, the usual drugs, and in addition, we're randomly assigned to either Ed lifestyle modification with meditation or to an educational class for lifestyle modification at this health education based on America Heart Association recommendations for people with heart disease.  And they were followed for an average of 5 years, maximum of 10 years.  And the investigators looked at heart outcomes as heart--end points of death, heart attack, or stroke as the composite outcome.  And when you look at that composite outcome, these are the event rates and the controls.  These are the event rates in the experimental group.  There's a 47 percent reduction in death, heart attack, and stroke in heart disease patients who continued usual medical care, and on top of that, added the experimental lifestyle modification program of 20 minutes twice a day of deep rest, this experience of restful alertness.  Now, this effect is as great or greater than conventional treatment, conventional methods to treat coronary heart disease or to prevent the reoccurrence of coronary heart disease as great or great as aspirin, lipid-lowering medications, or blood pressure-lowering medication.  But the paradox is that this people were already taking aspirin and Lipitor medications and blood pressure-lowering medications.  So this is like the discovery of a whole new class of medications for the treatment of heart disease.  In this case, these are endogenous medication, if you will, whether this is endogenous opioids.  Opioids are other neuromodulators that we've been hearing about today or others that remains to be discovered.  But these are antiatherosclerotic endogenous changes.  Part of this conference is about social implications of stress and social implications of stress resilience so I'd like to touch on some data which relate to public policy today.  We are across the street from the capital.  I'm not from any congressional staffers here or not that maybe there at least an ear shot, hopefully, or read the results of this conference.  These are data on health care cost utilization very much in the news today, health care cost.  These are data gathered from Quebec health utilization records, in Canada, there are centralized health care and centralized health care records and national electronic health record which makes studies of health care utilization under various interventions very practical.  In this case, investigators in Canada drew on the Quebec statistics and compared a group of high-cost utilizers divided into two, one who began transcendental meditation, the other group did not.  Both were matched in this non randomized trial but in this controlled observational study for demographic factors and healthcare utilization prior to learning TM.  And this is about the point of learning transcendental meditation, followed over 5 years time and there were significant reductions and healthcare utilization on the order of 28 percent.  These are physician payments.  There are other data showing in patient utilization also decreases the order of 40 percent.  So this is very relevant to treating and preventing chronic stress-related diseases which consume fairly substantial portion of our healthcare budget, of the Canadian healthcare budget, as well as the American healthcare budget.  I couldn't help but showing some sociological data today, we've heard in previous talks that social stress influences disease, we've heard about socioeconomic status, we've heard about catastrophes, these are data from The Lancet which reported on a natural experiment, that is the Gulf War in the Middle East and looking at heart attack admission rates to hospitals during times of work exacerbation.  This is the time of the beginning of the 1991 Gulf War and these arrows show missile attacks, episodes of missile attacks on Israel.  And then the investigators looked at the hospital admissions in Israel and show that there were correlations between heart attack rates based on hospital admissions and missile attacks.  So not with the people that were hit by missiles and that shrapnel caused their heart attacks.  But these are people who are in a social environment of war stress.  All right, so that's been fairly well-shown that social stress can influence cardiovascular disease, individual stress can influence cardiovascular disease.  We've talked about at least one method to reduce individual stress, one by one, our individual patients, in the previous studies.  But now, I'd like to show you an example of an experiment which attempts to reduce suicidal stress, collective stress in an attempt to improve collective health.  This was--these results of 3 social experiments, by my sociological colleagues, these were published in peer-reviewed journals and replicated 20 times and done independently.  So these were studies in 3 different countries where groups of people gather together to meditate.  In this case, the groups of people were circumcised, mathematically predicted to relate to social effects based on physical models.  These are square root of 1 percent of the population and these communities came together to practice transcendental meditation in some advanced programs and as measures of social stress, these are crime rates, drawn from the police departments in these various communities.  The police department had no interest in these experiments, if anything they had nocebo interest in the experiments, not believing they would work, but agreed to give the results to the investigators and the police investigators--police department ended up having representatives on the review boards for the studies and co-authored these publications.  The bottomline is that the reductions in crime rate in these 3 communities, when large groups of people gather together to meditate, which suggest something that's a little beyond the conventional medical paradigm but according to our sociological friends, there are social effects of stress and from these experiments, social effects of stress reduction.  So the criminal seemed to respond.  All right, so this leads into the paradigm that I want to conclude with today or actually both today and yesterday, we've been talking a lot about mind-body medicine and I'd like to suggest to you a new model of healthcare, several today's and yesterday's investigators Dr. Chrousos, who knows it would come after him, have really shown that this stress, or this mind-body connection in--has a pathological effect.
^M02:50:00
Now, what if we take this mind-body connection and we look at the other direction, can we create a new model of healthcare based on mind-body medicine, use positively or we could call this consciousness-based healthcare using the mind or consciousness and can we think of this as healing from within?  Why do we need a new model of healthcare?  Anyway, I couldn't help but show you some statistics from Barbara Starfield at Johns Hopkins who published in JAMA about 10 years ago but I don't think these statistics have changed very much that when we use conventional healthcare or in the conventional healthcare system, about 250 people, 250,000 people die each year from the side effects of conventional healthcare drugs and surgery.  And when you line this up, with the leading causes of death from conventional sources, modern medicine is a third leading cause of death in the United States.  So not only are we not preventing cardiovascular disease, it's rising around the world and our medical treatments are also killing people.  Therefore, if we could find side effect free methods, wouldn't that be a great contribution to conventional healthcare?  I think some of the data that I've shown you, reviewed with you today, suggest that that may be possible and when we look at a theoretical model, I'd like to expand your consciousness even more today.  It's not expanded enough already by taking some suggestions from my quantum physics friends who say that there are physical models for some of these mind-body effects that we've talked about.  So from the point of view with the physics, the world is made up of molecules, atoms and forces of nature, electromagnetism, strong force, weak force, subatomic particles and these are the various particles, quarks, leptoquarks, that make up atoms and molecules, these are the basic forces of nature and the most recent advances according to our quantum physical friends, are in unifying these forces, and they call this field where all the forces of matter, fields of nature are unified as the unified field.  String theory or superstring theory is the latest emergence of this field theory that Einstein originally predicted, theory of everything, according to these theoretical physicists, one field that gives rise to the physics, chemistry and biology of physical existence.  And according to the Vedic model and this procedure of meditation comes from the ancient Vedic model, that during this experience of meditation, we experience quieter and quieter, more inner states of the mind, until we experience a unified state of mind where there's no thought, no individuality, this universal state of awareness which can be paralleled at least to this universal state described by physics.  And more biologically, if we look at a representation of human physiology, here is a person, actually here is a person up here, sorry.  A person is made up of organs, organ systems like the heart, heart is made up of cells, cells are made up of macromolecules, biochemicals.  Eventually, from the point of view of genomic medicine, the DNA is at the basis of our human physiology but DNA is made up of the forces of biochemistry, forces of chemistry, forces of physics.  So the basis of our molecules is this physical field which is the basis of our physiology and the basis of society.  And what if we could experience that basis of the universe at the bases of our mind?  What if the mind and body were connected?  So if that we're all true, if we could transcend in our awareness, experience that common bases of mind and body, if we can enlighten that field of all the laws of nature, that field of balance, harmony and peacefulness in our molecules, in our physiology, then we could create balance, harmony, peacefulness and less diseases in our physiology.  So that is the theory.  That is our hypothesis and there's a fair amount of experimental test of that, which I have shown you today.  So we've talked about the Neurocardiology Stress and Strategies for Resilience, here's my contact information if you want any further information and all the data is in MEDLINE and PubMed also, so thank you very much.
^M02:55:04
[ Applause ]
^M02:55:09
>> Thank you Dr. Schneider, questions please.  We have a few minutes for some questions.
^M02:55:17
[ Pause ]
^M02:55:21
>> Yes?
>> In terms of you slides, do I understand the slides right to say that not only did health education not help but it seemed to harm?
>> Well, there wasn't a--there wasn't a no treatment control group.  So, one could say that or one could say that was a natural history of the disease.  Because people with cardiovascular disease and atherosclerosis tend to have progression of the disease overtime.  So, I'd rather think it was the natural history of the disease.  But, you know, one could test that.  Yes?
>> Any other questions?  Wonderful.  So, we'll take a lunch break and we'll find ourselves back here at 1:30, is that right?
[Inaudible Remark]
Yeah, that's very short break.  Is that all right?
[Inaudible Remark]
All right, so Dr. Brown says 1:45.  Thank you, thank you so much Dr. Schneider.
>> You're welcome.
^M02:56:37
[ Applause ]
^M02:56:43
Our next speaker, managing stress with transcendental meditation.  My new best friend Norman Rosenthal.
^M02:56:55
[ Applause ]
^M02:57:02
>> Thank you Joan.  Well, I feel very lucky to be able to follow that wonderful talk by Dr. Robert Schneider in which he presented some of the very powerful controlled data in relation to the cardiovascular system.  That was very actually influential to me in terms of becoming interested in this form of meditation.  Just to give you a little bit of a background, I am a psychiatrist for over 30 years and a researcher.  I was at the NIH for 20 years where I worked with the seasonal affective disorder and the light therapy.  And then for about 10 years, I ran a clinical trials research organization where mostly we worked with the drugs, in studying different drugs.  So, you could well be asking, well how did you come to be interested in transcendental meditation?  Well, in my practice, I have a bipolar gentleman who told me maybe 5-6, years ago, he said, "You know, whatever you're doing with your medicines is all very well, but what's really helping me is this technique that is steadying me from day to day of transcendental meditation."  Well, I had done this back in South Africa in the early 1970s off to the Beatles, went to visit Maharishi in Indian, Maharishi being the modern founder essentially, the conceptual founder because it's thousands of years old but he basically more than anybody single-handedly brought it to the west and the rest of the world in its current form, which is geared to make it feasible to the average westerner.  So I have done this in South Africa, but it was a fad of my youth, and so I let it lapse.  But now my patient was urging me to go back and try it again, and I thought, "What's the harm?"  So I got my technique refreshed, started doing it.  And he kind of was persistent in this, he's "Well, has it made a difference in your life?"  I said "Well, actually not really."  He says, "Well, are you doing it regularly like, twice a day?"  I said, "Well actually no, I'm not."  And then it occurred to me that any program whether it's a diet, whether it's exercise or whatever it is that you want to make a change in your life happen, it has got to be done regularly.  So, I--you know, give it a month or two and if it's not doing anything, so be it.  And that's really what I did and after a couple of months, to my astonishment, I found that change is happening in my own mind, my own brain.
^M03:00:01
And here were a couple of specific examples.  If somebody would get in my face to say something annoying or irritating, I had this tendency to zip them right back.  And this was operating on this kind of philosophy that if I didn't get my licks in quickly, you know, I would kind of lose the opportunity, and now, I would kind of find myself thinking, do I really need to zip them back?  What if I waited 5 minutes?  What would I lose?  And then of course after 5 minutes the whole thing becomes so petty.  And then another thing that I've discovered about myself, which I didn't realize is that, sometimes I would get some idea in my head that I was really upset about something.  Let's say I was upset with George Chrousos.  I would say, I've got to call George up.  I've got to figure out what's going on with this thing and we've got to have it out and got to discuss it blah, blah, blah, blah.  And what I was realizing is that I was binding anxiety and tension and anger with action, that suddenly I though if I called him and we worked it out, we sorted it out, we'd all feel much better.  But what really happens is when you're anxious or angry and you call somebody in that state of mind, then you get them upset and angry.  They'd pick it up in your voice and they'll say, "Why is he calling me?  Why is he so upset?  Something must really be going wrong here and you get their fight-or-flight response system activated.  And what I would find happening is, I would say, "You know, why do I need to call him now?  You know, it's not necessary, I'll think about it a little bit."  And then the whole thing would disappear and I would find myself doing something else.  In the next morning, I would send him a one line e-mail instead, which would totally take care of the matter.  So, I realized that it was really influencing my reactivity and my good judgment when it came to issues that get a person keyed up.  And I was thinking, you know, this is very, very interesting.  So, I did a little of my own research.  It's, you know, it was just more amount of research.  You'll see it, it's with PTSD and with some bipolar patients.  The numbers weren't large enough.  They weren't the beautiful controlled studies that we've seen here.  And I thought this is very interesting.  I started using it with my patients with anxiety disorders and other problems.  And then I thought, "Well, let me hit the literature."  And I was amazed to find well over 300 controlled studies, some of them, the ones you've just seen.  And when I saw this cardiovascular research, I thought, "You know, this is really potent, this data, this personal experience, I've seen it help patients.  Why don't I write a book about it?"  So that's what I did and the talk that I'm going to present is really a synthetic talk.  It really is a review of the literature and the thinking about transcendental meditation, organized in the same way that I'll organize the material for my book, Transcendence.  Now, we were just talking about what does transcendence mean, where does the word come from, so on and so forth.  And I had heard that it was a fourth state of consciousness, that they were--there was sleeping, waking and dreaming and then there was a fourth state of consciousness.  And I've been a psychiatrist for 30 years, but I also am a very skeptical person and it seemed a little bit of a woo-woo thing, what is this fourth state of consciousness?  I've never had the fourth state of consciousness and I'm whatever 55 years and so don't tell me about that.  But, I sort of tried to get into it and what I found was exactly what's being described.  That when one does the technique, thinks the mantra as you've been thought, the mind stills down until you get to a point where you're completely conscious, if a pin were to drop, you would hear it, but your nervous system is very, very calm and there's a sense of a disappearance of boundaries, that you don't know where you begin, where you end, what day of the week is it, what time is it?  Not that if somebody, you know, Jolta Devans [phonetic] asks you, would be able to tell them.  But it's that these things don't seem to matter right here and now.  They kind of evaporate and it's a very nice feeling.  It varies from session to session.  Sometimes it can be quite lovely and you can even have unusual experiences like maybe seeing a bit of light or having a sensation of your body moving in space.  But, most of the time, it's just kind of very simple and plain.  And what fascinated me about this state is that obviously it persists through the day to some degree between meditations or you wouldn't have a drop in blood pressure.  Six hours later when your blood pressure is measured, something is carrying over.  And, there are even other forms of consciousness that have been described and when I heard them, they also sounded a little outlandish to me until one day I had--I'd been meditating and I came to have my dinner and we have this place mats that we got at the museum in France where they've got Monet's water lilies in Boston and--and they're kind of I mean they're not high art, they're just like replicas and I'd eaten off of it many, many times, but I set down off to meditating and all of a sudden it was as though I was seeing this for the first time.  It was though I was right there in his gardens at Giverny on a summer afternoon and it was obvious that this feeling from the transcendence had kind of carried over and I was seeing things in a more fine-grained and detailed and beautiful way, and you know I wish I could say that it always happens like that, it only happened once.  I've had other experiences too.  But I think the important thing that I've realized is that this is not really something you do in order to get special effects.  If you get special effects, great, but you don't need to.  It's not a necessary part of the process.  But I think for us who were interested in the mind, it is just very interesting that there are these spaces and chambers of the mind that we don't necessarily interact with unless we have techniques to help us to do so.  So that's what transcendence is.  Do I press something here?
[Inaudible Remark]
Oh, the F would be the one, okay.  This is derived from an article by Travis and Shear who tried to characterize meditation into different categories.  For example, we heard Dr. Gold yesterday talking about focused attention and open monitoring and we did a lovely exercise with that.  Those are two kinds of meditation that had been combined into the mindfulness tradition, and the third one has been called automatic self-transcendence.  And the reason it's given that name is that although you're told to think the mantra, the process kind of goes beyond itself, so that you get into the state where the mantra can even disappear and you're just in the state, and then various the different kinds of meditation that fall into these categories.  Just for those who want the nuts and bolts, there's a lecture involved, there are some steps to learn, couple of lectures and interview, four teaching sessions of followup.  You're given the mantra and how to use it.  There is a fee that is paid to the teacher and these teachers are sort of very well trained, and it is a lifetime fee.  So, nobody ever has to pay again and it's very helpful to check in periodically.  And it--the money goes to the teachers who spend their--basically that's their whole profession.  This is my colleague, Dr. Fred Travis, hooking on a series of electrodes on the model and a lot of the brain research in transcendental meditation has involved the EEG.  And this is how Travis and Shear have tried to separate out the different kinds of meditation.  Looking at how much cognition is involved if you're focusing attention, then you're actively bringing your mind back at the drift.  So if you're open monitoring then there's a list of that, although you're asked to be aware as we were yesterday of the tip of your nostril.  And then notice the transcending part way, you're really asked not to be very aware.  It's intentionally supposed to be effortless and it's almost going on in the background.  So there's a decrease in the degree of cognition and therefore, there is as you would expect a difference in the EEG.  So I think this is quite an important point about meditation because it's banded around as if all meditation is the same thing.  And of course it is, and I think people really need to understand that.  I think as meditation gets more and more respect and as people begin to know more about it, you know I think it behooves them to distinguish between different concept meditation as though it's not just all like, you know, apple pie and you know, mother's love, it's just--you know, let's be specific, let's define exactly what's involved and then we can really begin to really turn it into the science that it deserves to be. 
^M03:10:29
Here are just a couple of examples of different kinds of waves.  The slower ones on the left are alpha, the faster ones on the right are beta.  And what you see on the left here, and every horizontal line here represents one of these leads that was put on this girl's head or in anybody's heads.  So each horizontal line is a single tracing.  What you see is the ones on the left are very much lined up with one another compared to the ones on the right.  They're--they're said to be coherent.  So coherence is a property of brain whereby different regions of the brain are firing at rates that are correlated with one another.  Now they may not be exactly lined up, there may be a lag as one region of the brain influences another or as a wave passes from one to another, there is a lag but the statistics builds that into the analysis, the so called lag correlation.  And I put this here because with TM, brains have been found to be more coherent not only during meditation but between meditations as well.  And this is a sort of cartoon showing the head from above in the upper two figures and from behind or the front in the lower two figures, and the one that sit on the right is from a person who is a meditator where you see more connections between these different brain regions than on the left.  This brain has got two regions flagged which we've already heard a lot about.  The golden region in the front is called the prefrontal cortex and the little gold ellipse over there is the amygdala, and we've heard a lot about these two things.  And basically, what happens through the meditation process is that the prefrontal--the amygdala settles down and quiets down and the prefrontal cortex, there is a balance between these two.  And I like to think of it for example in a corporation as the CEO who runs the show and then there is a fire marshal, and he really plays his role when there is an emergency like a fire.  And, you know, when the fire--when there is a fire, that fire marshal bangs on everybody's door and everybody has to get out of the building including the CEO.  So he takes over when there is an emergency.  But mostly in a good corporation, the CEO should be running the show.  Now what happens if you've got an anxiety disorder or a very stressed person is that that fire marshal is banging on the door day in and day out.  So, the CEO can't get any work done, and that's what happens with the prefrontal cortex.  And it's not just the distraction of the fire marshal banging on your door, it's the--the question of not knowing which time is it a real emergency and which time is it just a false alarm.  It's like the boy that cried wolf once too often.  When is it really an emergency?  So you have to be on high alert all the time because one of these knocks on the door could be a real fire, and then you'd be cooked.  So, a brain during meditation shows increased alpha waves.  That's a soothing type of slow wave associated with reflection and relaxation, but particularly in the front--prefrontal cortex it shows increased coherence in both alpha and beta waves.  Now I'm pushing this thing but I think I did something.  Oh, now healing, luckily I don't have to get into because Robert Schneider did such a great job, but this really would normally cover the terrain that he covered, and to me it's kind of necessary for that to go first because I think it establishes in such a solid way that something is happening with the stress response system.  And we can talk a little more about that, I'll just go right through these wonderful pictures.  Too--and this slide which is a metaanalysis by Kenneth Epley [phonetic] and others, and it's on 146 studies in which TM has had a much greater influence in reducing anxiety than the other techniques that had all been called stress management techniques.  Now this is a 1989 report, so it does not include the mind from the space stress reduction, the new work of John [inaudible] and others.  So, I think it would be very fascinating to investigate how do these two different techniques--do they produce the same effect, do they affect different aspects of anxiety.  I think I would love to see more of a conversation and a discussion going on between people who have delved and thought deeply about these different kinds of meditation because I think that they all must tap into different aspects of altered consciousness that can be used to help our patients and ourselves.  Let's look at one form of anxiety disorder that's unfortunately been all too much in the news and for good reason, and that is posttraumatic stress disorder.  It's been estimated to affect 1 in 7 of the 1.64 million US veterans of Iraq and Afghanistan.  Half of those affected had never sought help for their symptoms.  Half of those who had sought help were inadequately treated and of course, the resources of the VA systems and other systems that handled these people are totally overwhelmed.  So we really need to find other ways to help people help themselves really.  Not everything has to be done with complex machinery, with simulated battle scenarios and complex cognitive behavior strategies about how better to regulate your feelings if you think you've gone over an IED, et cetera, et cetera.  I mean there are some data that that works but it's complex, it's expensive, it requires special expertise and training.  How about a technique that somebody can do anywhere all by themselves without any special equipment?  That's what we thought when we recruited--I jump ahead of myself because there was already a study in the Vietnam veteran era by Brooks and Escareno [phonetic] where 10 veterans given TM training, 12 controls receiving conventional psychotherapy, and after 3 months, 7 of the 10 TM have said, "I'm done, I don't need anymore help."  But the control showed little improvement, which is would make sense because I wouldn't think that regular talk therapy would actually help them at all.  It's not teaching them to regulate their stress response system at all.  We took in--this was 5 subjects with really bad PTSD.  This is--these are different scales that I used.  The blue one is interesting 'cause it's the CAPS, which is the standard--gold standard scale for PTSD and it decreases by almost 50 percent by week 8.  Now, it's only 5 people but some of the stories were very, very striking.  One young man who would--being a driver of a Humvee had gone over an explosive device, an IED, had come back to this country, had gotten on an alcohol problem, was having flashbacks.  Every time he would go over a pothole in the road, he would feel as though he had gone over an IED.  He would have nightmares, disturbed sleep, and one night he woke up with his girlfriend in a choke hold because she bumped into him during the night and he thought she was the enemy attacking him.  And he settled down, the alcohol went way.  He focused on his studies and he said, you know--his girlfriend began to have more respect for him because he became more organized.  And we spoke and I know Joan and I were talking about attention earlier, and attention is such critical function of being able to do anything.  You have to be able to attend to focus.  And the fact is that if you're overwhelmed with stress, you're not going to be able to attend and focus your attention where you want it to be.  It's going to be taken to every emergency and every worry that you have. 
^M03:20:01
That's where your attention is going to go, so you're not going to get much done.  And this man, he was able to get through his degree.  He's holding a good job.  That was just one.  There were several with--similarly, there were three or four with similarly good results.  And this of course just merges them all together.  And, of course, controlled studies desperately need to be done but if you can't imagine how hard it is to get grants to do that, you'd think that the money would--people would be running to give you money, but it's not the case.  It's very hard, it's very hard to get.  Okay, I'm going to shift to drunk--alcohol and tobacco addiction, and I don't want to go in depth here.  There are 19 controlled studies in all in the literature.  They were done between 1972 and 1994.  So as a researcher, my first question would be, well, why did they stop?  If they were so promising, why did they stop, you know, 15 years ago?  Well, when you're dealing with a small field of research like this, a single person's influence has a huge effect, and Skip Alexander was that single person who spearheaded it.  Unfortunately, he was a brilliant man, he died before age 50.  And basically, the area has not been picked up.  We're trying to get people interested.  God knows we need help with our addicts, with our alcoholics and other addicts.  And here again, I mean, if you think of the sitting with the addiction counselor session after session, what are the causes of death, what are the resources involved in that.  If somebody can learn a technique that empowers them, that would be a very nice thing to do.  And I'm not saying we shouldn't use all the new tools, we should.  We should use, you know, Suboxone or Nicorette, or whatever it is that helps people--Antabuse, but it adds something that helps that brain part, that helps the stress part that is fueling pain.  We saw in that earlier presentation, if you can give a benzodiazepine, it helps the pain because so much of the pain is aggravated by anxiety.  So if the anxiety can be relieved, well, wouldn't that be great.  So anyway, I'm just pressing this button like there's no tomorrow.  Hold on.  Just don't give me a remote control, I'm dangerous.  [Laughter]  Anyway, so let's talk about TM in schools.  This is the Visitacion Valley Middle School.  The headmaster is Jim Dierke, a marvelous guy.  They called--this is in a slum.  I don't know if you know where it is you San Franciscans, but it's apparently bounded on three sides by a highway in a bad area, in a slum.  It's in the worst possible place and it was a middle school and they called this guy up the day before and they said, "We don't have a suitable person to run this school, so you will have to do."  And he took the position and it was apparently terrible, it was pandemonium.  One story I was told about how the school was is there was a huge adolescent of about 200 pounds banging a garbage can against the wall of the corridor and it was kind of typical.  There were fights between teachers and students.  It was just the place nobody wanted to be.  And at that point, there was the availability for grants for TM to be taught in the schools.  They called it the Quiet Time program, 12 minutes twice a day and Jim said, "Heck yes, why not."  And this actually wasn't a coincidence.  He says that one time when there'd been some very violent event at a previous school, he had told everybody, just put your head down for 10 minutes and let's calm ourselves down and he said he felt a change in the tone in the school after that.  So that was the sort of inspiration that had helped him pick this program up.  Well, in some years later, this is the change in the attendance before and after the Quiet Time school.  There's now a second school.  You see the red lines?  The red bars are before the introduction and the turquoise bars are after the introduction.  Both schools' attendance that was dropping before the introduction was now improving and grade point average had the same effect.  But the qualitative descriptions were almost more powerful than the data because people who've gone into these school say they just can't believe it's the same school, the atmosphere has been totally changed.  Jim Dierke went on to become the principal of the year for the entire United States based on this experience.  And they really, you know, there are thousands of middle schools sets a heck of a compliment.  Anyway, ADHD might also be helped in some ways because we, as you know, we're dragging our adolescents, you know, up to their eyeballs.  And I'm not saying that stimulant shouldn't be used, I use them myself.  But oftentimes they are stressed, and the stress at least aggravates the ADHD.  And sometimes a stressed child who can't focus and can't concentrate and is all over the place could easily be diagnosed as ADHD.  And instead of dealing with the stress which would be a much more complex thing to do, it's much easier to give them a pill.  But if you've got ADHD, then imagine you get up in the morning and you're late, you're late, you can't get yourself dressed, you can't get yourself organized, you've gotten distracted, you've got to pack your book bag, got to get everything in your book bag.  And you hurry because you are already late and you're stressed so you leave stuff behind.  So you get to school, you're already behind the curve.  So you get anxious, so you don't listen to the class.  But as people settle down, and there's a small series done by Bill Stixrud and Sarina Grosswald, as you--as people settle down, they are able to focus better.  And in the prefrontal cortex, norepinephrine and dopamine are involved in attention and in executive function.  And what's thought to be the case in some people with ADHD is that there isn't enough norepinephrine and dopamine.  And that's why the stimulants which basically act on these neurotransmitters may be helpful.  But in a stressed individual, there may be too much norepinephrine and in fact, there is data that if there's too much norepinephrine, it can also--it's like an inverted U shaped curve, too little is no good, too much is no good, I've called it the sort of Goldilocks porridge phenomenon where it's just got to be in the right place.  So I'm not saying there isn't a role for the stimulants, I'm sure there is.  But let's decrease the stress as well, let's focus on the TM as one way they may be able to do that.  Talking about Maslow's hierarchy of needs, we all know this wonderful pyramid with self-actualization at the top.  Studies have been done with self-actualization, they do have scales, believe it or not, that measure it.  And the TM appears to improve self-actualization as well.  It's interesting, you know, I mean I just think of myself, I haven't written a book for 10 years before this transcendence book.  I didn't have the inspiration, I didn't have the focus, I didn't have the passion.  Somehow all of these things came.  Now that's end of one.  The scientists in the room would be skeptical.  But I think a lot of people find that when you settle down and you calm down and your stress system isn't constantly being challenged, one way I see it is that the TM seems to act as a shock absorber.  I think what happens is that our stress response system is challenged repeatedly through the day, and we're probably having these spikes of blood pressure.  That's probably why the mortality--cardiovascular mortality is so decreased.  We probably keep having this reactivity and these spikes, and I've got to phone George Chrousos to have it out with him about this and, you know, on and on and on false, false alarms [inaudible].  And I'll use George Chrousos because I know what a great sport he is and that he won't--and he won't mind.  And may I say thank you for this wonderful symposium while I have your name up in my mind.  So in any event, I think that what the TM is doing isn't just modulating the stress response system.  And when your stress response system is modulated and that amygdala isn't firing, you're spending more time in your prefrontal cortex.
^M03:30:02
And you kind of like your prefrontal cortex, it's kind of a nice place to be.  You can think about what you want to do, you can think about whether you want to create something, or you have a little bit of extra space to decide what's important, what isn't important, and when--maybe I don't have to do this now and, you know, half of these emergencies if you don't attend to them right away, they disappear.  I just think of all those e-mails that I have to write after 10 o'clock at night.  The next morning, I don't have to write them at all or suddenly they've become very short into the points.  So, I think a lot of emergencies, at least in my own experience and those with my patients are not as urgent as they might sometimes seem to be.  This terrific data, and I won't dwell on that on recidivism.  This is a freely amazing study, Journal of Offender Rehabilitation.  And the numbers are large, starts off with a cohort of 241.  And these are felons, these are not people who, you know, snatched somebody's pocketbook or didn't pay their parking bill.  These are serious folks.  And the recidivism, as you see, is way down even after 5 years where the P is less than not one.  And I've looked at some of these case histories and sometimes these people have impulse problems and, you know, you look at them the wrong way and they can just as easily stick a knife into you.  But what a couple of these people that--whose histories I've read and I've actually--if you're interested in any of these, I've gone into a lot of individual stories in my book.  But one of them, one of the most amazing stories was a multiple felon named Pat Corum in San Quentin.  And he was one of these people who just would zap you literally if you looked at him the wrong way.  And what happened, he says though, he started doing TM and he says he remembers the moment of transition, it was when somebody in the penitentiary [inaudible] him and did something that got his--that got his [inaudible] up and he just walked away.  He said, it just gave me those two or three extra seconds to walk away and decide, do I want to have another murder rap on my name, or maybe there's another way to do this?  So here you've got the actual data, Pat Corum multiplied hundreds of times over.  I'll just end on harmony, it was the last point that I wanted to make in my book in here too.  I've seen couples meditate together and there's like a pool of calm introduced.  You know, oftentimes, a spouse will come home and, have you put the dinner on yet, have you fed the kids, did you stop and get such and such at the store?  And immediately, they're beginning to bounce off of each other their stress.  And to have this opposite experience of meditating together, bringing their stress levels down, going to a nice place in their minds turns out to be a very positive thing in many relationships, it turns out to be positive in groups.  And then of course, the question about whether, you know, if a lot of people are feeling better and being nicer to one another, it kind of creates a chain reaction.  How does chain reaction works?  I don't know, it may be through the simple social network mechanism.  People are now finding that if people in the group lose weights, it sort of has a contagious effect or if they stop smoking, the positive effects can actually be contagious, or whether it's working through some more esoteric mechanism such as Dr. Schneider alluded to, I don't know.  But it can only be a good thing for people to be in a better place and not be upsetting each other's nervous systems.  And I probably end on that note just to show you that is my book and that is my website.  Please come and visit me, I blog regularly.  And it's been a pleasure.  Thank you.
^M03:34:38
[ Applause ]
^M03:34:44
>> Thank you so much.  So, questions for Dr. Rosenthal?  Yes, please?  Say your name please?
[Inaudible Remark]
>> My name is Laura Elsie [phonetic] and I just wondered in your studies, if you'd found out if there is an optimum time for transcendental meditation or whether it, you know, that's an individual thing, 'cause I see myself wanting to set my day up with it.
>> Yeah, you know, it's a really interesting question and I think--I don't think there's any controlled study that people have done it then and they have done it then, and they find that that is better than that.  But you know, through long practice, people find that it's a really good way to start the day.  I will do it before breakfast, you know with--breakfast will increase your metabolism.  And so, to do it before breakfast, certainly before my morning coffee, you know, I would do that and then before dinner if possible.  But I wouldn't be slavish about it.  If something sort of changes the structure of my day, I could imagine doing it differently.  But those are good times and it's good because it's like, it like grounds the day into restful experience as it's very pleasant.  Thanks for asking.
>> Other questions please?  Yes, thank you, and say your name please?
>> E. Ferguson.  Is there an optimum amount of time to meditate? 
>> The amount of time that's recommended is about 20 minutes twice a day.  Now, somebody says, well, can I get away with 15.  Well, that's probably fine.  Some it's all--what about 5 minutes?  And they sort of--how little can I get away with?  And in my own experience, and again, you know, these things are empirically derived.  People do it and they find what--in my experience, 5, 10 minutes, I'm just kind of getting into it.  So, if I were to clip off those last 10 minutes, it would be like I would--it would be like I would take away the best part because it's like this first 5 or 10 minutes I've kind of settled myself down and I'm really in the groove.  I wouldn't want to take those 10 minutes away.  Then people say, well, what about doing it for an hour, I mean isn't it more better?  And there are certain kind of advanced programs but really you can get a tremendous mileage just from 20 minutes twice a day.  So--
>> Anyone else, yes?
[Inaudible Remark]
>> Yeah, I'm just intrigued by the residual effect and that--having done a practice obviously slowing down, pausing, having the environment, or anywhere.  But the--and this is something you just press to--you could think about it in terms of research.  What are the residual effects, you know, how fast his heart rate can backup, or other systems when you come out of meditation and you start your coffee or busy day driving your car.  And so it's not so much question as just intrigued about what are the different patterns of residual effect throughout the day before the next sitting?
>> Well, you know, that's really interesting because if you take an experienced meditator and a novice meditator and you look at their EEG, you will not tell the difference.  So the difference does not show up in the acute scenario.  The difference shows up in the between times.  And aside from the lower blood pressure which takes a couple of 3 months to kick in, I gather, there would be more coherence in the EEG, especially if these people--you know, these transcendent experiences that people have between their sessions, they're a little different but they--just nice feelings.  I was giving a talk the other day and it was a very good friend of mine who had arranged it.  And he said, you just meditated before, didn't you?  I said, yeah I did.  You see, you know, I can tell.  You're talking a little slower, you don't seem to be as cranked up, et cetera, et cetera.  So, something is persisting of a nice quality.  It's hard to really put your finger on.  But I think it's, you know, it's transforming because of what it does between even if you didn't have any fancy effects.  I've had people say, you know, transcend--I say--I ask them, what does your transcendence feel like, 'cause I don't know?  I close my eyes and the next thing it's 20 minutes and--but I feel great since I've been meditating.  So, the--it's the in between and I guess I'm feeling the deficiency of my response because it's very difficult to characterize with precision and it probably varies greatly from person to person.
>> Margaret.
>> Yeah, I'm Margaret [inaudible].  You talked a lot about the impact to sort of slowing you down, making you come or less likely to fly off the handle, what about people who would like to be a little more aggressive who--
>> Well, I'm so glad you asked that, [laughter] because--
>> I mean I'm--you know, I probably don't fly off the handle enough and--
^M03:40:12
>> Well, it's interesting that you asked because when I was touring around with my book, David Lynch, the movie director, joins me.  And he's a long time meditator and actually he has started a really wonderful foundation that has taught school children to meditate all around the world, and you know, just wants to fund people who will never otherwise be able to meditate.  Street workers, young girls on the streets of LA who have got terrible PTSD and are--they've done wonderful stuff.  And he's a wonderful guy, and I like his movies, but he's a wonderful, wonderful guy.  And he says that in the very first meditation he ever had, it was like somebody cut a cable on an elevator and he fell into bliss.  And he gets very excited when he talks about it.  So I talked about, you know, how it's kind of calmed me down, then he takes up the podium.  And he says, people used to say my movies were very dark and I should see a psychiatrist, he says, now I travel with one.  [Laughter]  But when Norman says the meditation calms him down, it makes me want to vomit.  I don't want to be calm, I want to be passionate, I want to be creative, and that's what the TM has done for him.  So, you know, we're all different in our brains.  And we're only different things.  Obviously I needed to be calmed down.  Maybe you're more like David Lynch, perhaps you should consider making a movie.  And--
>> Thank you, Norman.  Caroline?
[Inaudible Remark]
>> Well this is something of a devilish question.  You've been talking specifically about TM meditation.  But our moderator has been meditating for decades for another kind of--other kinds of meditation, and I wonder, Joan, if you would just comment or somehow--I'll just leave this broad, reflect on your own experience of the decades and deep meditation, and retreats that went on for sometimes 3 months, in a different tradition.  And what--is that experience like it--not that one is necessarily better than the other but just--if you could just hold that up in this context.
>> Thank you, Carolyn.  Here I started sitting and practicing Zen meditation in 1965, and--but I was in my 20s.  And, it is--there are many similarities to what the technique that Norman and Robert have described.  Specifically it engages the cultivation of altruism, more of compassion or kindness at the onset.  It also has a strong emphasis on the postural dimension that is our body actually conditions our mental continuum in a very significant way.  Another aspect has to do with the development of attention.  And so, attention has various expressions, whether it's focused attention, and Robert and Norman were describing that, where you bring your attention to selectively to an object, you're not dispersed, it's not divided, but it's very steady.  So, attentional balance is a really important feature that's developed with the steady meditation practice.  Another aspect of the practice that I engaged in is close to what Norman describes in terms of open monitoring or open presence.  And that is a quality of attention which instead of being focused like a laser beam, is actually reflective, panoramic, inclusive, nonjudgmental.  And it is usually not possible for individuals to produce that quality of attention without priming it with focused attention first, really stabilize attention.  And so, the features that arise in Zen practice are related to attentional balance, affective balance or emotional intelligence, cognitive control or metacognitive perspectives.  So, Philippe was speaking about, and I think he also--you referenced at this capacity to really reappraise situations so that you're not appraising them negatively or in, you know, it's sort of a sinking mind way.  And also, in various studies, there's been some quite interesting work done on immune response.  And this is where George and I have connected.  So I think as Norman was saying, to use the word meditation is like us using the word sport.  You know, sport refers to many different kinds of activities and meditation refers to many kinds of activities.  I'm not familiar--I've done the same meditation practice for, what is it, 47 years.  So I'm not familiar with transcendental meditation.  But I think that there are features that Robert and Norman have talked about which are similar to Zen meditation but there are some things about Zen meditation which are quite different.  I also--I'm not sure I agree with the dose effect analysis.  What Richie Davidson and other neuroscientists have seen is that expert meditators, that is the 10,000 plus hours practitioner which I think Robert is probably one of those.  I probably have--could classify my self as one of those.  Philippe, you're probably one of those as well, though you're considerably younger than me.  But nonetheless, I think that mastery over any technique, whether it's wood carving or meditation, takes about 10,000 hours.  And the dose effect that Richie has found for example in expert meditators who engage in compassion meditation are--these are quite distinct differences between an expert practitioner and a naive practitioner.  So I think, you know, it would behoove us since meditation is being introduced in many different settings but different techniques, TM in some settings, mindfulness and others, Zen and others.  I think it really behooves us to, you know, have a very, you know, this metaanalysis that you're speaking about, Norman, you know, for us to really look at the whole corpus of neuroscience research which is, you know, a lot is happening all over the world right now.  To, you know, have a more granular perspective, then we've been able to really have in the past decade.  And this is literally a field that's building.  You know, my own experience has been that, personally I--the word transcendence is maybe not the word I would use for what the purpose of Zen meditation is about.  The purpose is to be very present in this moment in an unfiltered way.  And not, you know, sort of not away from or more than, excuse me, more than but, you know, to have a very precise kind, compassion-based, attentionally balanced, realistic appraisal of this moment as it is.  So I don't think we would apply the word transcendence actually to--as an outcome we would be seeking in our practice.  So that was a good devilish question.  [Laughter]  Sorry I gave such a long circuitous answer.  Now Philip tried to get to me to give a talk here and I actually wanted to talk about stress among clinicians because that's the area that's been my area for many decades, but anyway, you gave me a chance for a small area, and thank you both.  So we'll take one more question.
>> I have a question.
>> What's your name and?
>> Kevin [inaudible].  Have there been any studies on the use of TM with individuals with hyperfocus hypervigilance?
>> Well, I'm not sure which these individuals would be.  I know that people with PTSD are the paradigm of hypervigilant people.  They are on the alert all the time, and they had to be when they were in Vietnam or in Afghanistan.  Here's a wonderful story that somebody told me of.  His patient who was a Vietnam vet, he was standing with his bride on his wedding day in his white tuxedo and a car drove by and backfired.  And this guy was flat in the mud right there.  Hypervigilant, ready to pop off very, very easily.  And so I think that the answer would be yes. 
^M03:50:03
Now, I don't know who else would be hypervision, but all the anxiety states are hypervigilant.  And Bill Stixrud is a neuropsychologist here in the Washington DC area and he's very open about how he was so anxious that two people in one week told him that he was the most anxious person they've ever met.  And that was 40 years ago, he's been meditating all that time and he--it has taken care of the anxiety.  So, I think the answer is yes.
>> Wonderful, so Dr. Spiegel.
>> Thank you.
>> And thank you so much Dr. Rosenthal.
^M03:50:42
[ Applause ]
^M03:50:47
[ Pause ]
^M03:51:32
>> Great, thank you.  Well, thank you very much George and Phil.  Thank you for organizing the meeting and thanks to the Library of Congress, you've been very gracious and I appreciate the tours and the magnificence of this building.  It's a wonderful reminder that governments do good things sometimes.  And the last talk reminds me that you certainly made the case that meditation is a lot better than premeditated murder.  So, I'm glad that you're moving in that direction.  What I'm going to discuss is what we've learned about trying to help people who are dealing with very complex and profoundly life-threatening stressors.  And so, altering one's mental state is one part of a much broader picture of helping people face life with cancer, and a disease that may well shorten their lives.  So, I hope to talk with you about stress and depression, and cancer, the concept of allostatic load, and particularly how endocrine dysregulation is related to cancer stress.  What we do in our support groups to help breast cancer patients cope with the disease, studies about effects of these interventions on survival, possible psychophysiological pathways that could mediate this connection and some conclusions.  In this conference, we've been treated to an array of factors from the biggest social and environmental factors down to individual mindfulness psychophysiological factors that can affect disease.  But it certainly should be no surprise to any of us that disease is not a bottom-up problem, that if you have cancer, you have two problems, you have some cells in your body that have gone back into cell cycle, are growing very rapidly, do not adhere to the kind of contact inhibition that normal cells do and can cause serious problems in the rest of the body.  So, in a sense a part of your body becomes the enemy.  And on the other hand, you have all the things the body does to respond to deviant activity within it.  And that's another part of the factor that is regulated by a variety of factors that affect life and health, including in particular social support.  And I think you've heard from a number of people who have spoken here that we are indeed social creatures, that we define ourselves socially, not individually.  That in fact if you think about it, the human infant has the most prolonged period of helplessness of any mammal.  If the infant could not engage his or her mother in caring behavior, could not form a social relationship, it wouldn't survive.  And frankly, we're pretty pathetic physical creatures, we don't run very well, we don't see very well, we don't smell very well, and our major advantages are the opposing thumb, which is a good thing, and a very large cortex that lets us form social relationship and make plans.  It turns out actually that social support is a powerful predictor of overall mortality.  This is from a review by James House in Science, and what he showed in a number of large studies is that those who are well-integrated socially have twice the overall survival of those who are poorly integrated socially.  This means that social isolation is as bad a risk factor for survival as smoking or having high serum cholesterol levels.  And yet we don't think about fixing people's social environments as a medical intervention and I'm here to tell you that I think it is.  It may interest you to know that the kind of social support that's good for you if you're a man is being married.  The kind that's good for you if you're a woman is not being married [laughter], it's relationships with other women, sisters, friends, family, which leaves me to the unhappy conclusion that having a relationship with a man does your health no good at all regardless [laughter] of your own gender and having a relationship with a woman does your health a great deal of good regardless of your own gender.  Many more people, due to the success in improving treatments for cancer, there are many more people living now with cancer.  In 1971, there were 3 million cancer survivors in the US.  As of the last year account of 2007, there were 12 million.  So while most people think of cancer as a terminal illness, it has really become a chronic illness.  And one of the resources we then have is a lot of people with the same disease who can get together and help one another through it.  Now some of the stress-inducing factors related to cancer are anxiety and depression.  This sculpture was actually done by a Dutch breast cancer patient and I think it's remarkable in depicting her despair.  But the other thing you should know is that it's the only work of art she did in her life.  And so somehow she sat down and created this sculpture, it's remarkable.  Adverse life events can increase the risk of cancer.  So stress can contribute to cancer risk.  It doesn't give you cancer but it can alter the risk.  This is a study done in Finland among 10,808 women.  And any single major traumatic event increased the risk of developing cancer--breast cancer in the next 5 years by 7 percent, divorce or separation more than twofold.  So a variety of major stressors can actually alter the risk of getting breast cancer.  Now not all study show that it's a complex thing but it's enough to keep in mind that stress adds to the risk of getting cancer.  Oksana Polish [phonetic] in our laboratory looked at the time from initial breast cancer diagnosis to relapse.  That's what we call in oncology the disease-free interval.  And the shorter it is, the worse the prognosis.  So the less time you have between initial diagnosis and the recurrence, the more likely you are to die sooner of the disease.  And what she found is a linear relationship between the nature and type of stress and the disease for interval such that those who had suffered a traumatic event had a disease for interval that was only half as long as that of those who had no stress in their history, and those who had a stressful but not traumatic event were in between.  So it suggests that once you have cancer, major stressors can be a factor in the rate of disease progression.  This is a French breast cancer patient depicting her sadness with the illness and depression that Dr. Gold talked so beautifully about is a major factor in many medical illnesses including cancer and the likelihood of having depression increases with the severity of your medical illness.  So cancer patients have--about one out of four cancer patients are clinically depressed whereas, in the general population, the rate of major depression is only three percent.  So they go together and that means that there are opportunities for treatment.  In addition, depression is a bad risk factor, so my colleagues and I published in the Journal of Clinical Oncology last year a longitudinal study in which we looked at the course of depression during the initial year, was it getting better or was it getting worse?  So it was multiple measures of depression and followed these women for survival.  I'll show you a number of survival curves, you've seen a few already, but basically, the idea here is each event of someone dying drops the line so that the more steeply the line drops, the more rapidly people are dying.  The blue line are the women whose depression was getting better, and the gold line are those whose depression was getting worse.  And you can see that over the ensuing 15 years, the ones who had a worsening depression in this baseline year died significantly sooner than those who did not.  So it suggests that depression is a comorbid risk factor for breast cancer progression as we know it is for cardiac disease as well.  So depression is--it makes people miserable in and of itself but it also worsens their prognosis as breast cancer patients.  And the average difference in survival based on worsening or better depression was more than 2 years.  So it's a clinically significant difference as well and it means that we have to attend to the psychiatric as well as the medical aspects of breast cancer.  As I mentioned, many breast cancer patients feel that their body has become the enemy.  My French patient viewed the villain cancer going on the attack here.  And there are multiple stressors living with cancer.  There's the fewer mortality, there's pain, there's important decisions about treatments, reduced physical abilities, mutilating surgery, withdrawal from normal social activities that make you feel good and affirmed, so it's a life changing experience. 
^M04:00:15
And the hope we have as one of my breast cancer patients said is, you know, my life has never been the same since I got cancer but in many ways, it's better.  So how can we get them to better rather than worse with all of these stressors?  Well you've heard about metabolic syndrome in this symposium.  You've heard about the--it's not just the one big shock of being diagnosed with cancer but it's an accumulation of shocks that really are the most serious problem represented by stress.  It's the day after day, hour after hour kind of stress that takes its toll on the body.  And this was defined in a very important article in New England Journal by Bruce McEwen as allostatic load, the cumulative effect of stressors on physiological response systems.  Repeated stress response activation has been associated with dysregulation of the HPA acces in a variety of adverse health consequences.  You've heard about abdominal fat, insulin resistance, coronary artery disease.  There are a number of things that come with repeated hits to the system.  And the HPA is a delicately regulated system.  The main point of this illustration is that there are multiple controls in the brain and in the body to trigger the amount of cortisol and what it basically does is mobilize glucose into the blood.  So are you ready to fight or flee?  That's very valuable when you're facing a saber-toothed tiger.  But if you're not, you don't want it on all the time because then you drain your body's metabolic reserves.  So there are ways in which, as cortisol goes up, there is negative feedback at the anterior pituitary, the hypothalamus at the base of the brain.  And these negative feedback loops stop the excess production of cortisol when they're stressed.  However, and this is a--it's sort of a depiction of that.  And as you heard earlier, norepinephrine will tend to trigger this response and the system will turn itself on and then shut itself off.  But what can happen with repeated stressors is that the system, if it's turned on and off, may either just stay basically stuck in the on position like this or stuck in the off position like this.  And you heard about patterns of cortisol where at a time when you should have relatively little cortisol in your body late afternoon and early evening round about now, you may have elevations in cortisol, and at night you may have elevations that can have profound physiological effects.  So, repeated stressors can lead to dysregulation of the HPA.  Now, waking up is a daily stress test as we all know from this morning and since I'm from California, which means it was earlier for me than it was for you.  So our cortisol levels, the blue line here were very high when we woke up this morning.  But as I said by now, they should be going down.  However, as Dr. Gold mentioned, people with depression often have high relatively flat patterns of cortisol throughout the day, so it doesn't decline as it should.  People with PTSD tend to have low and rather flat patterns so they lose this nice diurnal rhythmicity of cortisol.  We were interested in what those patterns look like among women with metastatic breast cancer.  This is a depiction.  One of my breast cancer patients had been a Silicon Valley engineer and when she got diagnosed with the recurrence she said, you know, I'm not going to die before I become what I always wanted to become, which is an artist.  So she quit her engineering job, she went to art school.  By the time she died, she had produced a large body of work and was teaching art as well.  And she marched into our support group with this dressmaker's maquette that she had redone to illustrate what had happened to her body with breast cancer.  And you see the radiation burns, the TRAM flap reconstruction for a modified radical mastectomy, biopsy scars here.  So the reminders of the disease are with patients all the time.  And what we found was that about three quarters of our patients had abnormal cortisol profiles throughout the day.  They tended to either just stay flat or actually increase throughout the day rather than have this nice normal pattern.  And when we looked at this, Sandy Sefton [phonetic] took the lead on this project.  She's now at the University of Louisville.  We found that the laws of this normal circadian rhythmicity of cortisol predicted earlier mortality with breast cancer.  So the ones with the fatter slope--the flatter slopes like this, the red ones over here died significantly sooner followed out for 10 years than those who had the nice normal patterns, high in the morning, low in the afternoon and evening.  So, disruption of circadian patterns of cortisol with an independent predictor of mortality, independent of all the other risk factors that we looked for with breast cancer.  And we found that it was associated with disrupted sleep, so patients who had these abnormal patterns tended to wake up more during the night.  And we're now analyzing data from an NCI sponsored study looking in detail at laboratory measurements of sleep in cortisol to understand better the relationship between these two.  So maintaining circadian patterns is a good thing.  And one of the lessons that I think you've heard throughout this but I'll emphasize is that to manage stress, and stress including cancer, you've got to sort of be in training, you've got to do what your grandmother told you to do.  Eat well, sleep well, and get plenty of exercise because all of those things are good for stress management and good for your body.  So what can we do to help people with anxiety, stress, and depression related to breast cancer?  Well, there are a variety of psychopharmacological treatments that I only have one slide to discuss, and then various kinds of psychotherapy to help people cope better with the illness.  And this is my psychopharmacology slide, it's the New Jersey Turnpike.  So what we developed was a treatment called supportive-expressive group therapy with my mentor and colleague [inaudible].  And it involved seven themes, we meet for 90 minutes once a week to face and discuss all of the problems that people deal with with breast cancer, we build new bonds of social support.  So, the fact that you feel excluded from normal life by having cancer is your ticket of admission to the group.  And one of the great things is you not only receive help, you give it.  Many of these women come to feel like experts in living, and I'll show you an example of how they give help to one another even dealing with very stressful events.  And we thought when we started this more than 30 years ago that we might be stirring up trouble.  Many oncologists said you're going to demoralize these women.  They're going to watch one another die and get demoralized.  And I'm here to tell you that's not what happens.  Indeed, through expressing emotion, through getting closer to one another, giving, as well as receiving support, they can detoxify their fears of dying and death.  They can focus on the problem, the ultimate problem none of us can answer which is that we die but how they die becomes very important.  They can reorder their priorities in life, improve communication with families, communicate better with their doctors, and learn to manage symptoms using techniques like self-hypnosis.  No, oops, sorry, wrong way.  So one of the things we try to do in managing the stress is convert anxiety into fear and depression into sadness.  We try to get people to look at what's troubling them enough that they can really figure out what it is that's triggering the emotional reaction they have.  Your emotions are your friends, they're not your enemy.  So figure out what they're telling you.  And as Dr. Gold mentioned, you know, one of his patients said, I wish I could have a good cry.  That's what we try to do is help people focus on what it is that's making them depressed or anxious.  Thomas Jefferson whose wonderful library we visited over here said, when angry, count to 10 before you speak, if very angry count 100.  Mark Twain said, when angry, count 4, when very angry, swear.  [Laughter]  So I'm here to tell you that Mark Twain was not a meditator.  [Laughter]  Shakespeare of course put it best.  He said, "Give sorrow words; the grief that does not speak whispers the o'er-fraught heart and bids it break."  We found actually that we could change the way these women manage their emotion.  And I think this maybe the first psychotherapy trial where we're showing in a randomized trial so people don't choose which group to be in, we assign them, that we could change the way they handle their affect.  And the yellow line shows that the women in our supportive-expressive groups over a year tended less to suppress their anger, fear, and sadness.  They would talk openly about it, whereas the controls tended to do it a little bit more.  And they felt more that they were managing their emotions better even though they were much less controlled.  So many people think it's like Pandora's Box, if I start to cry, I'll never stop.  And they learn, as many meditators do, that if you just watch the storm go by, you can understand what's happening and manage it better.  So what I'd like to do is show you an example of how we try to do this in the group.  We talked very openly about death and dying, we grieve losses in the group.  When one member died, Madeline wrote these little cards that she distributed to the group.  Dear Eva, whenever the wind is from the sea [inaudible] and strong, you are here.  Remembering your zest for hilltops and the sturdy surf of your laughter gentles my grief that you're going and tempers the thought of my own.  So this is one of our groups when they learned that the first death had occurred in the group.  He has such a gentle way of asking questions.  [Laughter]  And, you know, he was right.  I mean, that was the essence of what we were doing.  Moyers told me later that journalists are people who explain things they don't understand, which I appreciated.  But he was right, that's what we were doing.  And yet, you could see a lot of sadness and pain in the group.  But they were learning to face death and they were learning to--at focus on the aspects of death and dying that they could do something about which is, to let people know sooner so you can say your goodbyes.  So even with death, they were finding some aspect of it that they could manage, which made them feel less helpless. 
^M04:10:02
Now, let me see if I can resume the show here, okay.  One of our members put it very nicely.  She said, what I found in the group, being in the group is like that fear you have standing at the top of a tall building or the edge of the Grand Canyon.  At first, you're afraid to even look down, I don't like heights.  But gradually, you'll learn to do it and you can see that falling down would be a disaster.  Nonetheless, you feel better about yourself because you're able to look at it.  That's how I feel about death, I can't say I feel serene but I can look at it.  So we tried to help people face the worst.  And I'm convinced that after more than 30 years of doing this, that this helps people, it strengthens them, it doesn't weaken them, although not everybody gets it.  I'm sorry, Mr. Randy, our test show you have two weeks to live.  And he says, can I take them in August?  He didn't--[laughter] didn't quite get the concept.  It's a terrible stressor for families.  And we try to help their families communicate more openly and clearly with patients about what they want and need.  Patients often feel punished by their treatment and reluctant to talk with their doctors.  So we encourage them to communicate clearly, to give the list of questions at the beginning, not the end of the appointment with the doctor, and to find doctors who can respond to what their needs and concerns are.  Well, does this help people or not?  There are side effects to any treatment.  He's saying, do you remember what you were feeling before you ate the other members of the group?  It's a rare side effect.  But we actually found in a randomized trial that women who were in our group for a year were less anxious and depressed than those in the controlled condition who got more anxious and depressed, randomized clinical trial.  And we replicated that finding 15 years later.  It just takes about 15 years to do one of these studies.  And we got the same result, basically more reduction in distress in the treatment group than the control group.  We also taught our patients a self-hypnosis exercise.  Now, there was a question earlier in the placebo lecture and one thing I--I'm not--it was a fabulous lecture but I don't agree that you can't give yourself your own placebo.  And in fact, what we do is teach people self-hypnosis so that they can learn to reduce or even eliminate their pain by altering perception in parts of their body, imagining a sense of cool tingling numbness, you can literally reduce pain.  The pain system is, as you heard, a top-down system as well as a bottom-up system.  So you stub your toe, the signal goes up through the lateral spinothalamic track into the brain.  But descending input from the cortex, as you've heard eloquently today, can change your perception of pain.  As you see here, the baby is getting the shot here and the father is the one who's in pain actually.  So this is an electro--an evoke-related--an event-related potential study we did.  And the big picture here is that the normal brain response to a series of shocks administered to the wrist is the red line, this one here.  But if you hypnotize people and give them exactly the same set of shocks and tell them their hand is in ice water, you see that the brain just shuts down perception of the pain.  So it's--and very early, this is tenth of a second after the shocks are administered.  This P100 wave just disappears.  The P200 and 300 are only half as big.  So it's not just that they react differently to the pain once they feel it, they literally change how much pain they feel.  And you can teach people this as a self-administered placebo, only stronger actually than the placebo effect.  And parts of the brain involved include this anterior cingulate cortex you've heard about as well as the prefrontal cortex that tends to inhibit response and somatosensory cortex as well here where you process pain signal.  So you can really change the pain that you feel.  And indeed, we found in this randomized trial that women who were in our group therapy wound up with half the pain that the control group did on the same in very little amounts of medication.  So it can be a powerful analgesic and has the added advantage of giving people a sense of mastery, a sense of being in control of the experiences that they're having.  And this is another one that we replicated a mere 15 years later.  So, given the title of the talk that Dr. Gold asked me to talk about, let me tell you what we found about not just quality of life but quantity of life.  We--at the time we did the original studies, Carl Simonton was writing a lot about how you could visualize your white cells killing cancer cells and lo and behold, it would happen.  And I thought it was an interesting idea except I didn't see any evidence that it did happen.  And what you could then do is make people feel guilty for not visualizing well enough when their breast cancer progressed.  So I thought we knew we helped them emotionally.  Wouldn't it be interesting to see what happened to them physically?  And I was not expecting much.  But what we found was very surprising.  This is another one of those survival curves.  And what you see is that by 48 months, all of the control patients had died and a third of the treatment group were still alive.  It was an 18-month median difference in survival, favoring the intervention group.  Now all the three of them did eventually die of breast cancer.  These women were not just hanging on and miserable, they were doing very well in these outline years.  There were no differences in treatment that they received, chemotherapy and radiotherapy that could account for the difference.  They lived better and it turned out they lived longer.  So, this study has attracted a fair amount of attention.  Last time I counted on Google Scholar, there were 2,222 citations to it.  Some very excited, some very critical.  Let me tell you what has been discovered since we did that study.  We did a replication trial.  And what we found was that the type of breast cancer you had made a difference now some 20 years later.  So women with estrogen receptor positive, better prognosis breast cancer, we didn't see any difference between the treatment and the control groups in survival.  But, among the women with estrogen receptor negative, a poor prognosis breast cancer, they got the same treatment effect that we had seen in the original study.  Now there could be many reasons for this.  But one that we think is plausible is that the hormonal treatments for breast cancer have gotten a whole lot better in the last 30 years than they used to be.  And this is a study showing that mortality is going down in breast cancer in the last several decades largely because we are blocking estrogen in women's bodies.  We're blocking its production, we're blocking estrogen receptors, and they're living longer with breast cancer.  So it may be that the one group that is exempt from that effect, from that benefit, are the ones who have estrogen receptor negative breast cancer.  So it could be that that's the reason for the difference between our true studies.  Recently, Barbara Andersen in Ohio State published a randomized trial using group therapy of a more educational cognitive behavioral kind than ours was but many of the same principles.  And she found also lower rates of relapse and mortality in women who were randomized to group therapy than control patients.  So independent study, same result, and this is a 10-year followup that she published a few years later showing the same effect, that these women continue to live longer if they were randomized to group therapy.  Recently, in the New England Journal of Medicine, there was a study in what you might consider the worst possible setting.  It was palliative care for people dying of non-small cell lung cancer.  And they were randomized to get palliative care or to have routine cancer care at the Mass General Hospital.  What they found was the women randomized to the palliative care had less than half the depressive symptoms than control patients, and they lived two and a half months longer on average, a statistically significant difference, in the setting where you think there was no possibility for longer survival.  So just providing emotional support, control of pain, treating depression, even at the very end of life with a very bad prognosis cancer resulted in longer survival.  So the tally to this point is that eight randomized trials show that psychotherapeutic intervention of one kind or another result in longer survival with various cancers, which is pretty surprising.  I wouldn't have bet that 30 years ago.  There are seven other studies that show no difference in survival.  In about four of those studies, there was no emotional benefit from the intervention so it's hard to imagine that there'd be a survival benefit.  In some, there was emotional benefit than no survival benefit.  So we still need to do more research but I'm glad to say that the studies are not random.  There are no studies that show that psychotherapy kills cancer patients.  None of them make them worst, some of them make them better.  So in the last few minutes, what I'd like to do is discuss what we think maybe going on that could link emotional and social support to slower progression of cancer.  And there are a variety of possibilities that involves stress management, the endocrine hypothalamic-pituitary-adrenal axis system, immune function, and a few others as well.  There was a recent study that showed that cortisol itself, if you take normal mammary tissue from mice and you put cortisol on it, the cortisol inhibits the expression of the gene BRCA1, this is a cancer control gene that when mutated, elevates the risk of getting breast cancer from about eight or nine percent to 85 percent.  So if you inhibit the function of that gene, you may be enhancing the risk of developing cancer.  And there's reason to think that steroid hormones like cortisol may inhibit expression of that gene.  We also found that high cortisol levels and depression in our cancer patients was associated with lower delayed type hypersensitivity.  This is the old TV test that you got where you had, you know, a little bit of tuberculin put under your skin, and two days later, you see whether you've got swelling and a bump.  If you do, you've got a cellular immune response to the antigen.  This is a pretty low-tech and crude but in vivo measure.  It tells you how the body is actually functioning. 
^M04:20:01
And it shows that patients who were depressed and who have high levels of cortisol tend not to have--be able to mobilize the same level of immune response which can have consequences for cancer as well.  In fact, the women in our groups who had these more abnormal diurnal patterns of cortisol had lower numbers of natural killer cells.  Natural killer cells have a CD56-positive antigen on their membranes.  They kill, transform the dying cells, including cancer cells.  And women with lower NK cells are more likely to die sooner of breast cancer.  So there is special class of lymphocytes that are involved in cancer surveillance and we see fewer of them in patients with abnormalities of diurnal cortisol.  This is a cancer patient's image of what she was like before and how she felt getting treated.  Some recent publications from Thaker and Sood and colleagues has shown something else that's very interesting.  And that is that this is an animal model but showing the daily stress with the secretion of norepinephrine, you've heard about norepinephrine as the hormone from the adrenal medulla that increases your heart rate and blood pressure, will also stimulate vascular endothelial growth factor, VEGF, which causes blood vessels to grow and can make a much nicer home for cancer that has metastasized.  'Cause one of the challenges for cells invading a new part of the body is to secure a blood supply so that they can get nutrients and oxygen.  VEGF helps them to do it.  And if you have more VEGF around, they're more likely to do it.  So they showed that norepinephrine will trigger more VEGF and more tumor growth.  And that if you block the norepinephrine with drugs that block it like beta blockers or with inhibitory RNAs that block the production of it, you actually slow the production of VEGF and the potential stress-induced growth of tumors.  Now this sounds a little abstract, although they have some very interesting pictures here of the growth of blood vessels and tumor in animals that were stressed here versus those that were not.  But they have a model that was sufficiently compelling, that people got an interesting idea.  There's a drug called isoproterenol, it's a beta-blocker that is used primarily to treat high blood pressure.  They figured there're a lot of women with breast cancer who also have hypertension, and some of them will be treated with beta-blockers.  So if there's anything to this, the women who happened to be on isoproterenol for their blood pressure might actually have a better outcome than those who don't.  And sure enough, propranolol, not isoproterenol I'm sorry, propranolol is the beta-blocker.  And propranolol, in fact, women who are on propranolol had better survival than women who were not.  So, the beta-blockers actually seemed to have a clinical utility in blocking the rate of progression of breast cancer.  So drugs that affect our stress response systems actually now seem to have an effect on cancer progression as well.  Finally, you heard a little bit about telomeres yesterday.  Telomeres are the ends of the DNA that help the DNA to replicate.  As they get shorter, we age basically.  And Elizabeth Blackburn who won the Nobel Prize for this a few years ago, Elissa Epel, Firdaus Dhabhar published a very interesting study showing that high stress was associated with shorter telomere length.  So the idea is that, basically, stress ages you.  And it turns out that this is also related to cancer incidents and mortality because as the telomeres get shorter, DNA replication gets more unstable.  And it's more likely to lead to tumor genesis.  And so there is evidence that telomere length which can be potentially controlled by stress may also have an effect on the rate of cancer progression.  So there are a number of pathways that can connect the way we handle stress and face it, our social support, our emotional expression, and factors like norepinephrine, cortisol and even telomere length that could plausibly affect the rate of breast cancer progression.  We think that cancer stress is like--it is best handled by facing rather than fleeing fears including fears of death, altering your perception including modulating pain perception, coping actively, expressing rather than suppressing emotion, and enhancing social support.  So the ideas to convert one from someone who feels mutilated and scared to someone who like the Winged Victory of Samothrace, you don't look at that beautiful sculpture on the Louvre and say, oh my, there's a woman who's missing her arms and her head.  It's an image of transcendence and that's what we try to help these patients do, and they help one another to do it.  Now you would think modern medicine would have made more of this already.  He's saying, I'm sorry Mr. McConnell, your insurance plan only provides for empathetic nodding and a side and downward glance, could you turn up the volume, I want the Supreme Court to hear this.  [Laughter]  There's a 200-dollar co-pay for any additional words of compassion not to exceed 40 words or three expressions of sympathy or condolence.  So I wish it were funny, it's actually true.  And the fact that medicine has been colonized by the insurance industry is hampering our ability to offer patients the kind of support you heard about in the placebo talk, the kind of support we offer in these support groups, the kind of positive expectations patients need.  And one other fact I will leave you with is that the hated inefficient bureaucratic government health insurance system, Medicare, which does underpay us somewhat for our work.  You know what their overhead cost are?  2.7 percent.  You know what the overhead is in private insurance?  27 percent.  So, private insurance is 10 times less efficient than government-administered healthcare.  And people don't seem to get it or understand it.  And all the money that could be going to pay physicians, and nurses, and psychologists, and social workers to help our patients cope with their illness is instead going into the coffers of the insurance industry.  And I think that's a tragic mistake.  Thanks.
[Applause]
Thank you.  The other thing that kills me, forgive me for one other comment.  Have you ever heard a mother proudly say, there he goes, my son, the provider.  You know, the term provider to me is as insulting as any ethnic slur.  I didn't go to medical school to be a provider, I went to be a physician, a doctor, a clinician, there are lots of respectful words.  When European nations colonized Africa, they came up with demeaning terms for the natives to justify taking over their countries.  And that's what's happened with healthcare in the United States.  And it's a real tragedy because we know here that what we are doing can help patients live better and live longer, and our ability to do what is being actively interfered with.  Well, my French cancer patient, and the French have a great healthcare system by the way, said, you know, you have some good days, she felt attacked by her cancer and she did the particular thing that French do best, she made a meal of the crab, her cancer, and says, [foreign language] which I pass on to all of you.  So, in summary, stress and its management affect mind and body.  Circadian cortisol and other circadian rhythms mediate this relationship.  Depression and psychosocial support may affect cancer progression as well as quality of life.  Feeling better may lead to healing better.  It's not just mind over matter, it isn't.  But mind matters.  I want to thank the patients who gave generously their time and effort to help me bring this to you.  This is our Center on Stress and Health, and they're a great group of researchers and clinicians.  I want to thank our funding from the National Institute on Aging, the National Cancer Institute, the National Institute of Mental Health, the California Breast Cancer Research Program, the Dana Foundation, and the MacArthur Foundation among others.  Shakespeare said, "When we our betters see bearing our woes.  We scarcely think our miseries our foes.  The mind much sufferance doth o'erskip.  When grief hath mates, and bearing fellowship."  But remember that the mind-body relationship is nothing to fool around with.  He's saying, what happened here, sergeant.  He says it's a placebo overdose.  We're pretty sure he only thinks he's dead.  [Laughter]  Thank you for your attention [inaudible].
^M04:28:14
[ Applause ]
^M04:28:19
Thank you.
>> Thank you so much, Dr. Spiegel.  So, questions please.  Yes?
>> Yes, ma'am?  Yeah, there we go.
>> My question is, you know, and again I'm speaking as a layperson, I've--
>> Sure.
>> --made that very clear.  Is that--aren't those recommendations that you made basically good for the general public?  Because what I find with American society is that people try to pretend like death doesn't really happen.  And so therefore, it's something that none of us can avoid.  And then when people get there, it's as if they are surprised.  So I remember when Frank Sinatra died, they expressed surprise that Frank Sinatra died.  Frank Sinatra was pretty old when he died.  So, you know, I mean it was inevitable, but don't you think that these are things that we should incorporate basically into our conversations and our relationships.
>> I think you're absolutely right.  You know, we do pretend that death doesn't happen.  Frank Sinatra was actually dead several years before he got in.  [Laughter]  You'd never know.  But you know, I have to say, one of the things that appalled me the most about a lot of things in the first 10 years of this country in this decade, was the decree from the previous president that there would be no images of dead soldiers returning back from Iraq.  And I thought, what is this?  What disrespect to the sacrifice these people are making, and to pretend that it doesn't happen.  And the worst thing is that what passes for a press in this country obeyed the order which blew my mind frankly.  I don't understand that in a free country.  There was a woman in Los Angeles who had herself buried bolt upright in the front seat of her Maserati. 
^M04:30:03
And so she were just going to drive off somewhere underground.  And the worst, the worst part of all this, you know, there's a wonderful old spiritual, you've got to walk that lonesome valley by yourself.  How do we comprehend death?  We can't really understand non-being, but we do, by being alone, isolated, separated from a loved one.  So what do we do when people are dying?  We isolate them 'cause we don't talk about it and I think one of the things that makes these groups, but you're right, for many other people to work, is that at the moment when you're most terrified, you're not alone with that terror, you're with other people.  And that counters that dread about death because you're with other people sharing it, so I think you're absolutely right.  We have gotten ourselves into a lot of stupid situations by not seriously looking at the consequences of what we're doing.
>> It reminds me of the Woody Allen joke, I'm not afraid of dying, I just don't want to be there when it happens.
>> When it happens.  That's right.
[Laughter]
>> But I think your point is so well take and, you know, we've introduced sex education to schools.  I think it's really important to make mortality, the truth of it more evident--
>> I agree.  I agree.
>> --in our educational systems.
>> Yeah.
>> The natural world will teach you if you look into it.
>> Yeah.  Well it's, you know, it's a sort of American obsession with winning above all.  You know, sooner of later, we're all going to lose on that score and you might as well--and in fact what we found is the reason we started these groups was that the existential victim that you don't really live authentically until you face the contingency of life.  And what we found was these women lived more authentically because they were facing their mortality, 'cause they knew they weren't going to live forever.  So, you don't waste time, you trivialize the trivial.  Irv Yalom said, cancer cures neurosis.  You know, you don't have time for it.  And so it's an enriching experience, it's not just facing a loss, it's enriching.
>> Well, I think Plato said the same thing.  You know this encounter with our mortality is the very bedrock of the spiritual path.  More questions?
>> Yes?
>> Yes?
>> [Inaudible] Have you studied the application of these group scenarios with some of the other stress factors we've talked about today?
>> Well--
>> Such as substance abuse, poverty and the others?
>> Yeah.  Poverty, that's a big one.  Substance abuse, sure.  I mean if you look now, you know, with all the medicalization of treatment for substance abuse for example.  To be honest with you, any doctor will tell you that the best thing we have for alcohol abuse is AA and it's not perfect.  But people get in a group together, they understand one another, they say, "My name is Fred, I'm an alcoholic, I am powerless over alcohol," and they support one another, day in and day out.  And frankly most of it, you know, it's sobering to realize for example that heroin was invented to treat opium addiction, and methadone was entreated--it was invented to treat heroine addiction.  And so you kind of you get the picture that we're--we're trying hard but we haven't gotten there.  So, certainly, self-help and mutual support is terrific for substance abuse problems of various kinds.  Poverty is a bigger socioeconomic problem than that.  But frankly, people who have a common problem getting together and dealing with it together in person and increasing now on the internet, can often be a real genuine help to one another.  So yes, I think it's a model that can apply in many different--and if you go any disease now, you go on the internet, you'll find a disease oriented group with--often with group meetings of one kind or another and that's a good thing.
>> Thank you so much.  Any other questions?  Yes?
>> Yes sir?  Yeah.
>> I'm a massage--oops.  I'm a massage therapist for a living and I've been--and most of my clients come to me for pain management work for back pain, slip discs, things wrong with their body.  And in the course of working with people, I've had the opportunity to work with a number of people, either women with breast cancer, or folks with--one client with bone marrow cancer.  As their therapist who spent time with them, I ended up getting the questions they couldn't ask their doctor.  I ended up being the one to point them to counseling groups to try and get them involved in support groups.  For those of us who are at this end of offering therapy where I'm not involved in research 'cause it's not what I do, what should I--what kind of training should I try and get so I can help my clients better?
>> Well, that's a nice question.  I think there are, you know, it depends on--you know, each of our specialties have certain kinds of training programs that give us some added skills.  And, you know, when you're--it's a very intimate thing to be touching somebody's body and I suspect it opens up a lot of intimate feelings and desire to discuss.  I think if there are programs that sort of teach people what's called active listening where you can kind of listen and merely just say back to the person what they've said, where you're not judging it, you're not answering questions you can't answer, but just responding and keeping the emotional tone open.  You may have noticed in this movie that when Sheila started to cry, there was profound silence, nobody was rushing in to reassure her anything, they just let her cry.  So just being open to the expression of emotion and perhaps engaging in some active listening can be very helpful, and then pointing them in the direction of some, you know, more focused support for their illness can also be a very good, good thing.  Yes?
>> [Inaudible] over here in DC, you mentioned in person and internet, is there any data or anecdote and qualitative differences between the two?
>> Well, it's still early, there haven't been--there are beginning to be some very good studies of internet-based support groups, we did one a number of years ago when the internet wasn't nearly as fast.  And so people were in a synchronous group, so there was a leader and 10 members, but they were typing and you were watching the type show up on the screen.  It actually worked surprisingly well, we actually saw significant reductions in depression.  There are now some research programs in UCLA ,University of Wisconsin using either iPads or iPhones so that people can get in touch with one anther when they have a problem and they have a kind of network set up like a Twitter network or if they're in trouble they can be in touch.  I think we're going to know a lot more.  I would say what we know so far is that they work surprisingly well actually.
^M04:36:26
[ Inaudible Remarks ]
^M04:36:31
>> I can, I can tell you that my students in my stress management course at AU often accuse me of having group therapy as opposed to they expected to come in and be taught how to manage their stress.  And the way I run the class was in a circular, typical therapy circle and they were shocked at how many of their stressors they had in common with others.  And although it took them over the course of a few weeks into the semester to realize they were not that unique, they were shocked at how much stress was relieved just knowing they were not the only one experiencing it and learning what they could control and what they couldn't control.  And it was a very effective method for them and--
>> I'm very glad to hear that.  It makes perfect sense and a lot of the additional stress, you know, Dr. Gold talked about the kind of the anxiety about the self.  And if you try to take responsibility for things you don't control, A, you can't control them, and B, you feel bad about yourself for no good reason.  So when these women in our groups get together and they see that you know what, there are eight other people whose friends started getting weird on them when they were diagnosed with breast cancer.  And it isn't 'cause they forgot their birthday or couldn't go to a party, it was because their friends are freaked out about their having cancer and they don't know what to say, you feel very different.  And the other thing is that you are there to give as well as receive help.  So you've learned how to deal with some of these things, you can help someone else do it, and that makes you feel better about yourself too.  So, this kind of interaction you learn a lot and you also learn to help a lot and that makes you feel much more in control of whatever these stressors are.
^M04:38:06
[ Inaudible Remark ]
^M04:38:12
>> Isn't it, it's nice as a teacher and as a therapist to be made to feel pretty irrelevant.  And your job there is to set it up and get it going and make sure--and there will be bumps along the way that you need to deal with actually.  There are bad groups as well as good ones.  You know, there is somewhere, you sort of stir the pot and then nobody talks about it and they jump on to something else or somebody dominates, you've got to deal with that.  There's a skill involved in running it.  But the people come to feel correctly that they are the ones that are helping one another and it's true, that's what you're there to make happen.
>> And I want to appreciate what Dr. Chrousos said to me last year with regards to what interventions were relevant in relation to stress.  And, you know, he talked about diet, exercise, sleep.  But one of the vectors that you addressed was relationship.  And I also remember there are two other, by the way.  One of them is flow and the other one is doing good and being good.  You know, living a life that's meaningful and is beneficial, I really appreciated that list you shared with me. 
>> Yeah.
>> So, I would like to--you'll be available for questions at the break just so that we stay--
>> Yeah, I will at the break, yeah.
>> --within the constraints of time, is that okay?
>> Sure.
>> And we'll take a 15-minute break and then Dr. Reissman will do her presentation followed by Dr. Chrousos.  Thank you so much, Dr. Spiegel.
^M04:39:42
[ Applause ]
^M04:39:45
>> Dori Reissman, Dr. Reissman is going to give the next talk on acute and chronic effects of stress and strategies for resilience.
^M04:39:56
[ Pause ]
^M04:40:08
>> Good afternoon, I get myself oriented on here and then we'll get going and there we go.  So I'm Dori Reissman.  I'm coming to you today from across the other side of the district for the Centers of Disease Control.  And I was asked to talk about stress in work, I think the title that might have been in the program was acute and chronic stress and strategies for resilience.  Well, I'm going to focus this on the issue around work and specifically emergency response work.  If you're curious as to why I'm wearing this uniform, I'm part of the public health service which is one the seven uniform services in the United States.  We don't have the same military grade weapon, we just have our mouths and our brains.  So we go off trying to fight disease that way.  Okay, so when we're thinking about worker protection, people who work and how they get not hurt and not sick because of the jobs they do, we think rather broadly and stress is a big piece of that.  The question is, what is it about stress?  Is it something we can avoid?  Is it graded in some way?  I think earlier in your conference, you heard a bit about the chemicals involved, the parts of the body that have neurological connections, neuroendocrine system, and all those things that I saw reflected in Dr. Spiegel's talk as well.  These are all things that we have to take into consideration when we're thinking about work and stress.  Except you have the extra added layer that there's an employer involved, or if you're a self-employed that you've done this to yourself.  So, let us think about preventing injury, preventing illness, looking at the environment around us whether it's this podium and the fact that I could fall off here if I didn't have a good sense of balance.  This is a workstation for me at the moment.  Or think about operational considerations which might be, if you're in a office setting, your operations might be answering the phone and pretending that, you know, various methods need to be done to follow through on request or having computer algorithms to follow when certain request come your way.  So operations can go anything from office work to out in the street when you see law enforcement officers or firefighters fighting a fire, or policing a scene.  Those are operations as well.  When we think about exposure, you're thinking about exposure to everything.  The air we breathe, the people we talk to and have to interact with, some of whom we have to listen to, the way in which our own mind is able to function, how we fit it in terms of our lifestyle and dietary habits, these are all environment depending on how big you want to make it, and what the outcome is that we might want to measure.  And I'll talk about that in a couple of minutes.  One of the things that becomes very important in a work setting is thinking about the resources that are available.  Resources are people, it's equipment, sometimes it's just time.  And those resources become incredibly important when we're considering what the issue of stress might be.  I'm not exactly sure how you heard about stress in the very beginning of this but a lot of times when I talk to audiences that are not in the research realm, they're not in the heavy science realm, it's helpful to put this in terms of a pathogen or, you know, you could think of it as a cohabitator just like the bacteria that are in the air, colonate your airway and your food tube, your esophagus, that's the same thing.  Stress caught us constantly but when does it become something that invades our ability to fend off, our ability to bounce back?  And when is your system overloaded and can't respond the way it should?  I think about that in terms of resilience and that's more of a term of art, if you will, that's been emerging in the past 5 to 10 years.  I'd say I started looking at the question of resilience around when 9/11 happened in 2001.  And at that point, resilience was not a common word in anything but child psychology.  So the word really came at that point from child psychology but I've heard lots of definitions of this.  Anything from comparing it to resistance which would be like a steel bar that you try and bend and if you are able to finally bend it, you overcome its resistance you break it, you don't--you're not able to bend it back.  To a rubber bar that if you take it out of its normal equilibrium and you let it go, it springs back into place.  I'm thinking of it more along those lines.  When you bend out of shape but you can spring back to yourself, okay.  It's the early adaptation to being bend out of shape or stressed in that distress kind of way.  Adversities can be anything.  In the work place they could be a bullying situation or a really bad match between you and the people that you have to answer to or having to produce more than you possibly can and in with die or circumstances if you don't like loss of a job.  I find resilience as a very useful concept when you think about it organizationally.  Any of you who do work know that a company does well when the culture behind it is supporting the workers and supporting the positive aspects of the worker's life.  That positive aspect isn't just having a baseball game that the employees play against each other.  But it goes all the way into all the employee policies that might be made for how much leave time do you get, whether you can tell a work, whether you have to punch a clock, how strict the people are about protocol whatever that protocol might be for, how managers are allowed to instruct their underlings, if you will, is it allowed to be rather abusive, is it allowed to be overly constrictive.  These are all elements that are tied to the productivity of your workforce.  So if you think about that broadly, it is organizational dynamics.  Now, because I work at NIOSH, which is the National Institute for Occupational Safety in Health.  Safety and health was the long time, the thing that we used to think about.  But there's a third leg in that stool, that's been missing for a long time and that is resilience.  You can be safe and you can be healthy but not resilient.  So they're not the same, they overlap, they interact and it's difficult to get some of these points across specially in the federal government where I work and trying to make a difference on the kinds of workforces that we are dealing with and I primarily, I'm dealing with hazardous occupations like fire fighting, law enforcement, constructions, mining, agriculture, these are dangerous jobs.  So, you ask and you can see why, you know, the miner there comes because we have a big division of mining.  We mine for, you know, we look at the workers and all the commodities but coal is a very big thing and has had an accidents in the recent several years that have hit all your newspapers.  So the question would be resilience.  How does it affect the worker?  How does it affect the work place?  Does it affect how long somebody stays on the job?  That's staff retention, yes it does.  Does it affect how well you can recruit people?  Well, a smart person who is looking for a job who's not desperate okay is going to talk to the co-workers and get a sense of what it's like to work there?  Can I see myself work there?  Do I want to be there?  Or is just really a cready place?  Okay, is it really not so much fun and not a good thing?  What's the morale?  What's the motivation behind?  What make people thick?  For me, at Centers for Disease Control, the thing that makes people thick there is acquisition of new knowledge, making a difference in peoples' lives in terms of their health and that really is the motivating force.  Sometimes, you know, you can go to other federal government, departments and agencies and see that what makes a difference there might be perhaps whether you're able to protect the environment in a successful way.  It's not so much about the human beings, it's about the plants and the animals and the dirt.  I can't call it dirt, the soil.  I had roommate in collage, she didn't like the word dirt.  So when you're thinking about health and safety, you have to really be thinking about what are the cause?  If you are a boss, you want to know what the cause, what the bottom line is.  How many workers compensation claims arise out of stress?  I think you probably heard about stress related to blood pressure, to ulcers, to arthritis.  Okay, that those are three already very costly medical conditions, heart attacks, strokes, and I can go on in cancer.  I think is there's also connection with stress in cancer as you heard a lot about and very much enjoyed that talk sir.  So the worker compensation claims, if people are becoming stressed or they're becoming ill from chronic illnesses, their mind or they have a lot of things going at home that takes their attention away from their job, they're distracted, they're more likely to not be thinking about what they're doing in the moment and if the job that they're doing is physically or psychologically hazardous, you're chances of making a mistake and getting hurt or sick from that are much higher.  So there's a connectivity to all this, so I'm trying to make it very practical and bring it back home.  Right now I'm the medical director of the World Trade Center Health Program which is the federal response to what happened in 2001.  And I can tell you that disability and early retirement totally affected the New York City Department of Firefighters, the Fire Department of New York.  They lost half their force either to retirement.  I'm not even talking about the 343 who died that day but they lost half their force to medical disabilities.  You know, you think about these things and you think that's a large event and so that's something you can really focus your efforts around.  But then there's the everyday events that happened that might not be so traumatic but they can really squeeze the life out of somebody while they are trying to earn a living for their family.  So for those of you in the audience who actually are in the research realm and like to see these kinds of logic models, if you look at your left, you're seeing the worker demographics, what's the supply of labor that's going into that?  What's the technology?  What's the economy?  No matter how large a societal variable you want to look at, you could put it on this particular logic model, it would fit.  The next thing as you come over is, how is a job organized?  Everybody has an organization to the work that they do.  Some of it self-imposed, some of it imposed by the nature of the work itself and other times you have in positions made upon you because of somebody who bosses you around and wants to do with a certain way just because they said so.  So the way an organization practices, the way your job is designed has a huge impact on stress.  That's different then what you see below which are the physical and chemical exposures that we usually think about in safety and health.  So I mentioned mining before.  Mining, you're going miles underground in a very dark environment.  That's very dusty so you have to think about knocking the dust down so you're not breathing them, getting black lung it it's coal, or getting silicosis if it's other kinds of mining.  So you're thinking about these things plus with the darkness and the noise of the machinery, you loose hearing, you loose some sight.  There's a lot of things that people compromise by being miners, okay.  So those will be good examples of a very tangible, physical and chemical exposures.  But how does the exposure, the work organization, how does that interact with us as people?  That's the mechanism box and it varies quite a bit.  It could be biologically, you could become a sick.  There was something in the air like your co-worker decides that they're going to take their mental heath day on the day they're feeling well but when they have the flu, they're coming to the office and they're going to give it to you because that's what the flu does, it just jumps around to people very quickly.  So there's a biological mechanism, it's also a behavioral one if you want to think of it that way.  But a different kind of behavioral mechanism might be just not paying attention to the safety restrictions you should have at work.  There was a case that I investigated long ago when I worked in New York City where there were window washers, it--that happens to be a father son business in the family and they do the high rises and they have to strap in so that they don't fall.  Well, sometimes they don't strapped in because they're bigger than that, they're stronger than that, it's stupid, it's a waste of time until their body falls several stories and smashes on the street.  And then you have the entire business affected by that.  That's behavioral, that's judgment and behavior.  So cognitive kind of what is in there with judgment and behavior.  So then the last column here would be what are the kinds of outcomes we would look for?  What we would we measure if we wanted to do this either for policy, for laws, for research?  What do we want to measure?  You can measure illness, it's tangible, somethings broken or it's not, it's ripped open or it's not.  Psychological injury is a lot harder to measure, a lot harder to measure.  Something is going wrong with the body system.  Your blood pressure going up is a dysfunction.  When it becomes hypertension is when it sustains not going down to safer levels where you risk affecting your heart or you risk stroke that's when it's labeled hypertension and interventions are done either with dietary changes, lifestyle changes or medication.  So that's when you're in disease.  All these things interact with each other quite a bit.  So I added something to the chart.  This part of it it's not on the NIOSH website because I've been fighting that fight for awhile, but traumatic experience is in there, that's the disaster, the bad incident, the horrible thing that happens at work.  I think recently in Ohio where the gunmen came to school, that's traumatic incident for the teachers, for the security people, for the clean up people, and the students, okay?  The resistance and resilience is something I spoke about earlier.  Resistance is also important.  We try to do things with resistance by dressing warmly enough, eating well enough, not going outside, getting soak and wet and then stepping into a freezing cold area, right?  That would lower your resistance to infection, affects your immune system.  But we can think about resistance psychologically to trying to support somebody's ability to deal with their emotions, okay.  And then the last thing that belongs on the very last column is recovery, which nobody seems to really talk about, they talk about what's wrong but not what's right, at least in most of medicine.  So I'm going take another step back again to the work organization just to see if I didn't cover some of these.  And I think some of them are out but this is just to open your mind to a different way of thinking about stress that maybe you hadn't been before.  But how many hours in a row you work before you take a rest?  That's the work-rest cycle that tends to be more of an issue with manual labor, very physical labor.  But since I don't have--that's not my job I can tell you it's a problem because I'll sit in front of my computer doing my mental thinking and writing on the computer for hours before I realized when my dog comes over with his leash, he says, "It's been 4 hours, I want to go out now."  That's the only reason I get up, it's not because I remember that I should.  And at that point when I stand up, my back is stiff, my legs hurt, I might start getting a headache.  And I'm not unique, this is what you hear all over the place, these are white collar jobs.  This is where we've moved to instead of the service industry, we've moved to a lot of this kind of intellectual stuff with computers, with phones sitting still and that's a problem.  The job design or things that we spoke about, how much controlled you have or how your job is designed?  If you think about it as, you know, a long line of things where you're making sausage you might have piece meal stuff and you have no choice but to do a repetitive motion over and over and over again, you have no control over what you're suppose to do.  You're stuff in the sausage into the linings, that's your job, period.  Versus somebody who might be a middle manager, who has to be able to take complex information and move it upward.  And you also have to be able to take complex information and break it into its component parts to get the workers who are working for you to do their job and to do it well so that you shine.  There's a lot of different skills that go in to job design and interpersonal skills.  I love the fact that there was a lot of--at least in the last talk there was a lot of discussion about social support.  Social support at work is just as important as your friends outside of work because where do you do spend most of your day at work?  The only other place that you spend it is in bed sleeping.  And you might be having support there but it's in your dream, it's very different, okay?  So when we're thinking about building what we can about resilience in organizations and resilience in workforces, we really have to think about job design, interpersonal supports, managerial training, mission and culture.  And you have to think about the career of the people that you're working with.  They're not there just to be commanded, they're there to grow because taking meaning in your work that you do is often a motivator for people, it's not just to earn a paycheck, it's making a difference, it depends on the level of skill they have and how much control they have over the kind of work that they are really going to do it all.
^M05:00:10
So, the thing I have down here I think it's an orange, yeah, orange or yellow down there.  When the requirements of a job or a bad match or a poor match to the capabilities resources or needs of the worker you have negative job stress.  I'm just going to let that sink for a minute, mismatch between person and environment.  And there's been a lot of research on that.  If you're thinking about things that are potentially traumatic, meaning psychologically traumatic.  If you're afraid for your life, if you get a severe injury and you don't know how you're going to function after that.  And you can't control it.  And you can't predict it.  These are all the adjectives use for trauma that go in a bad direction.  If you lose the things that connect you to this world whether it's a loved one, a loved place, or that's a physical place, or loved place in life, your station in life.  You don't realize you have one until it's taken away.  And that's what disasters do.  They take these things away and people see that.  And then there's sensory overload.  You know, one of the things I was thinking about when I was listening to Dr. Spiegel speaking, he was talking about social support and I immediately--in the internet.  And I thought about, "Huh, social networking, I kind of avoided that because I find it to be sensory overload.  I wonder if that's something that we can't teach in the younger generation."  How to use social networking to build the right kind of information flow that supports them as a person?  That might really change the way a lot of the internet and these other things that we do or use in the future.  So to move a little bit quicker here on some of the issues around, what it's like to be in an emergency responder?  How do we think about emergency response?  There's a life cycle to health and safety.  We think about it before an event happens.  When an event is going on?  When you're leaving that event as an individual and also as the agency that employes you and then what happens later.  At NIOSH, we've created this, in case there's anybody here who's really interested in emergency response, I urge you to go take a look at this particular document.  And I think this will be up on the website eventually so you'll have access to it.  A lot of what we learned in 9/11, in Katrina, in all the disasters that happened in between, the SARS, which was the Severe Acute Respiratory Distress syndrome, the Anthrax attacks, more recently the gulf oil spill.  All these things are teaching us the same thing.  When we're thinking about the first part, I guess when circle my finger here you can't see it, so I'll just sit here and do that and then I remember how to speak.  But the deployment phase, when you're sending somebody out there's responsibilities of individual to look over the health and safety of those individuals if it's done right.  There's an assessment of the exposures that the workers are facing, okay.  Unfortunately, emergency responders are just a different group, everybody else runs away and they run in.  So there's a different psychology in these people to begin with.  They're the once who need to rescue and save and preserve life and environment.  But who's looking after them?  We have federal laws, we have state laws that are suppose to protect them by the devices they wear to help their breathing or the clothing to prevent being burned, et cetera.  But you have to have a lot of infrastructures in place to be able to assess what's going on in order to prevent those things from happening.  I could talk for hours and hours on this one slide.  But I won't bore you to death on that.  It's surprising to say that all of these requires the right preparation, none of these circles exist, nothing we can do happens without preparation.  And preparedness is the worst funding of all, okay.  Actually I just probably second to recovery; recovery is not funded at all.  Preparedness get some funding, event response gets all the attention 'cause it's sexy and that's the way it is, that's just human nature.  So I put the slide here in order to give you a feel of some of the complexity.  This is the tracking model, if you will.  You have workers that progressed through these arrows and so, you know, you've got people who are on a roster that should be sent to the field, deployed means they're sent away from their home office and they're put somewhere, in a disaster setting or emergency setting.  They're monitored through the incident operations, there's a command structure to all that.  All this time there should be environmental sampling, safety compliance, assessment of situational problems.  And then somebody's ready to leave the scene and go home.  Now, you're at the tracking option decision.  What do we do with this person, do we watch after them, do we let them go, or do we do some kind of health monitoring to them?  Should we examine this individual before they leave the site, or shortly thereafter?  If you're working with a bunch of small firms, how do you have a sense of the magnitude of the impact of anything unless you have a larger body looking over the group?  These are the kinds of things that we're doing in the federal government, but I put this here because it really pertains to almost any group that you would be working for if suddenly everything changed and you were on in an emergency status.  You'd become the responder 'cause the person on scene is the responder, no matter what label they get.  For those of you who do know things about law enforcement and firefighting, there's an incident command structure to all of these.  This is a typical way that you see it operations, planning, logistics, and finance and a commander, and then these people who tell them about things like a public information officer.  And they usually have a safety officer there.  I've showed resilience into that box and that was novel, they've just hadn't done that before, and we're trying to get that message out.  So if you want to think about your workforce, you want to think about the place that somebody you love works in, they can build their own Responder Resilience Program, their own Internal Resilience Program.  It's not that unique.  In psychology, you're really looking at what is the organizational goal?  If they're the target of a nasty thing happening, that's one thing.  If they're responders to a nasty thing happening that's another thing, if they're both like the police department and the fire department was in Louisiana when Katrina hit and the flood occurred, they were both, the responder and the victim.  That's a different set of psychologies to consider.  What operational support is available to really do an assessment?  And then this was my social support piece, always have a buddy.  No matter where you work or what the situation is there has to be at least one person, one person that you can at least talk to.  And choose them carefully 'cause you don't want to choose the buddy who mind your business, and you don't want to choose a buddy who doesn't get along with anybody else 'cause then may not really serve your needs.  It's a triangle affair, it's you, your buddy, your family, that's the triangle of support because sometimes it's the buddy that deals with your family 'cause you can't.  This was the self care and coping but it sounds like you had quite a bit of an opening on this earlier, perhaps yesterday.  But, how do you take care of yourself, you know, there's a lot, you can do on your own.  I like that self-hypnosis and changing perceptions, I think I'm going to follow up and figure out how to do it.  Technical assistance and assessment is the step 3 from that Responder Resilience Program I was talking to you about.  That's really understanding, what your job in the field?  What are you trying to assess?  And making sure you have what it needs to get there and that you have backup support.  Evaluate how things went, how did it go?  Make changes.  For some of you in the business world it's called CQI, Continuous Quality and Improvement, that's the older term for it.  But it's the same idea, it's always funny because you hear in emergency response, "Oh, let's do a hot wash 'cause everything comes out in a hot wash."  Or, "Let's do an after action report."  But, what they always do is scrub all the nasty things out of the after action report 'cause they don't want anybody to know about their blemishes.  So we don't actually learn, we just keep reobserving the same thing over and over again.  So what can we do to support the workers?  How can we think about on larger corporations that have resources that can actually look at stress, anger and grief management?  It's very similar.  When something goes wrong, really wrong with your workplace, you're only human; you're going to have the same reactions.
^M05:10:06
What is continuity of operations?  That's the ability for your workplace to be able to do its basic function, should its building be disrupted, should its technology be disrupted, should key players be knocked out?  But, you might want to use that term continuity of operations for your family.  What is the continuity of operational plan in your family?  Should something happen to you at work, something happen to them at school or whatever it is.  It's a great philosophy to plan around.  So, the last part of this talk is sustaining resilience.  We talked about, resilience as concept of early adoption, early adaptation to adversity, it can happen as an individual and in every layer of an organization to a large firm, making sure that the message of resilience is instilled through all the different administrative policies that are created.  If workflow is adjusted, technical support is available, and the big one which all of us are probably guilty of, not balancing home and work.  In our 24/7 culture now, my Blackberry goes home with me, it's great because I can take care a business all the time.  And that means I never get away from business.  So, how many of you have had a son or a daughter tell you, "Could you put that away and listen to what I'm saying?"  Or you're driving down the highway and you realize you're driving and you're still texting.  How many accidents are caused by that?  So, we really have to look at these questions in a societal way, maybe it does come down to a legal framework to make driving illegal with texting, making driving illegal with phones.  Maybe there was a real reason for that and maybe there should be something greater.  So, I think I've covered all the things on this slide.  I'm going to end with this one.  It's a very complex slide, but if I could actually size this shapes properly, which I couldn't do 'cause I didn't have the graphical knowledge to do so.  Resilience goes in the middle and depending on which one of these things you've squeezed to make a smaller resilience can get bigger.  There is a relational situation here.  So, if you're able to manage distress responses to a traumatic event or chronically stressful event, you're able to decrease the worry, the disruptor of your compromising behavior or to get better night sleep or improve your productivity, you are already exhibiting better resilience.  There's health risk behaviors too when people are stress.  They tend to do things that are--that continue, if you will, a pattern of pathology.  Some people become very aggressive and might pick fights or be short tempered and blow off their friends, or the ones they care about.  Others might speed, very fast on the roads, very jerky driving, not wear their seatbelt or worst yet, they're drunk and they can't judge things well and they kill somebody else.  Others disappear and you can't find them, they're hidden, they're isolated and that's where depression happens.  So, all these things interrelated and that really is the purpose of my talk, the interrelationship and our complex relationship with work.  So, I'm going to end their and thank you for your attention.
^M05:13:50
[ Applause ]
^M05:13:56
>> Are there any questions?
>> Yes?
>> Okay, just something crosses my mind also that in the day-to-day suffering at work?
>> Yeah.
>> Jealousy and gossiping.  Is there any research, occupational, psychology research on the effect of gossiping and jealousy in the workplace and it's corrosive?
>> That's wonderful term.  It is corrosive, the toxic workplace, the bully--you know, that's a bullying.  It is a bullying thing and there is a lot of research on that.  I can't coach on the researchers offhand but there has been a lot more work done outside of the United States that there's been inside the United States on that topic.  Although some of our national surveys are starting to pick up some elements to measure that so that we have something to compare it to and research that's trying to be funded this day and age.  So, it's a huge area, in fact the big one even in the military too.
>> Any other questions?  Okay, hold on, just a second, I wanted to check, George if you want to give a recap?
>> Very briefly.
>> Okay, surely.
^M05:15:16
[ Pause ]
^M05:15:22
>> We had another wonderful day today and I want to--first of all thank all the speakers and the participants for this very lively meeting.  After Dr. Gold's recap, I was very happy to hear Dr. Ensminger's lecture on Stress and Socioeconomic Status.  A very nice analysis based on data.  And the lecture of Fabrizio Benedetti on Placebo and Nocebo Effects in human societies.  I think having read his two recent books, I can say that he presented much less than what he really knows.  And from reading his work, I can tell you that placebo and nocebo is very powerful in our societies, well beyond treatment of patients.  Even there, you know, there are many things that have happened that are important and we don't realize it.  You know, people read now in the back of drugs, of the drugs boxes, all the side effects.  That's a nocebo effect, people develop the side effects which they would have developed, they have--haven't read those papers.  And it's well beyond that, I'm pretty sure that all methods of stress control employ resistance that are effective in placebo, which he didn't mentioned but I can tell for sure it's the stress system, which inhibited by placebo and stimulated by nocebo.  It's a reward system, which can go either way, either feeling well or feeling bad, depending on positive or negative thinking, which is again placebo versus nocebo.  And other systems that I've just--assisting these two particular systems.  When I looked at all the--in [inaudible] studies that he has put there for a various methods of treatment including cognitive behavior therapy, acupuncture, and so forth.  Central, to all of these were these two systems that I've just mentioned.  So that placebo and nocebo are part of our lives.  Dr. Roberts Schneider then presented the Neurocardiology and Strategies for Resilience and I think the data are very clear.  They are good control studies showing that meditating or doing something that relaxes your brain or part of the day helps, for how you feel, the rest of the day.  And, I'm not sure about the unified field, I don't think there's evidence for that, but I'm convinced that the various methods of meditation would actually started from the east.  The eastern methods and we find very little support for existence of these methods in the west.  Do work.  This was continued by Dr. Rosenthal who gave us his take on the Transcendental Meditation.  Now Rosenthal is a good scientist, he is somebody who's done research for many years, he knows what a control study is, and he knows to believe or not to believe results.  So I pay much attention to what he says, and the same is true for Dr. David Spiegel.  There's no question and he--you saw the data that social support but that's what he does is, it's very important in today's societies where families are broken down and there is no support system in our lives where we lived.  Few children usually find a way, you know, so the parent with that kind of cancers stay alone somewhere, it's not easy, so the society has--I think have duty to provide this kind of help to individuals who have cancer.  And finally, Dr. Reissman gave a wonderful lecture on resilience and I wish all counties and all organizers on the systems have this kind of controls to ensure safety and most importantly to predict that something might happen and prepare the workers to deal with the unexpected or the traumatic.  Is there any other thing you want to bring up that we could discuss?  Personally, I'm very happy with what we've learned in this conference and I hope in the future we'll expand it and do more.  Carolyn.
^M05:20:39
[ Pause ]
^M05:20:44
>> Yeah, just the comment that I seen touch on in some ways, who many of the presentations although not very explicit is a kind of tension between what we think of it, a need to be efficient and organize and now that's cost effective in medicine or efficient in organization or--I don't know what a tension between that and the power of the human relationship and the very ancient wisdoms that have developed overtime where--when technologies were in fact very primitive and organization are fairly simple at least compared to our current organizations.  And some hope I think that through greater reflection, or wisdom, or personal practice, or support among one another that there can be some ways in the modern world to compensate both for what we've created for ourselves and in some way to retrieve or reenforce what that ancient or they're not even so ancient, it's older knowledge about human compassion and interaction.  And I just see that theme of tension throughout.  I could say more of it, but maybe I don't mean to say more--
>> Well, I know what you mean, you know, humanity.  We want to have humanity.  What's happen to physician for example is not good for anybody.  Not for them and not for the patients.  We know now that trust and interaction the physician is a great predictor of how the therapies going to go.  So by having the physician just say a few words and go to the next patient, it doesn't work, you know, just take a drug and go home.  It doesn't work this way unfortunately.  So you have to recap this, take it back, develop it again.  It's going to happen I'm sure because the way it is, it doesn't work.  
^M05:23:16
[ Pause ]
^M05:23:21
Anything else?
^M05:23:23
[ Pause ]
^M05:23:28
Well, thank you very much.  And I hope we'll see you sometime in the future, all of you.
^M05:23:36
[ Applause ]
^M05:23:39
>> This has been a presentation of the Library of Congress.  Visit us at loc.gov.