. >> rose: welcome to our program. tonight a special edition, the charlie rose brain series 2, in the second episode we focus on depression. >> it is during that moment when you slip and trip before you hit the ground, the out of control terror but last, instead of lasting for a split second it lasts day after day, you are terrified of everything, and not even know what it is you are terrified of. this is very common disorders worldwide, about five percent of the population suffer from depression at one time or another and in the united states it is the major disability and people between 15 and 45 years of age. >> rose: episode 7 of the charlie brain series 2, underwritten by the simons foundation, coming up. >> the charlie rose brain system

is the most scientific journey of our time. made possible by a grant from the simons foundation, their mission is to advance the frontiers of research in the basic sciences and mathematics. >> funding for charlie rose was provided by the following. >> we are always committed to our supplies, the farmers, the fishefishermen. it is really about building this extraordinary community, american express is passionate about the same thing. they are one of those partners that help guide you, whether it is finding new customers or a new location for my next restaurant. and we all come together by restaurants, by partners in the community, amazing things happen. to me, that is the membership effect.

>> rose: additional funding provided by these funders. >> and by bloomberg, a provider of multimedia and news and information services worldwide. captioning sponsored by rose communications from our studios in new york city, this is charlie rose. >> tonight we will continue our study force human brain examining one of the most widespread disorders, depression. depression describes a group of conditions characterized by significant and sustained periods of low mood. symptoms can include persistent sad, anxious or empty feelings, fatigue, appetite, loss and thoughts of suicide or suicide attempts, approximately five to seven percent of the adult population in of the united states will suffer from a form of depression during any year. the lifetime risk may exceed

15 percent. our understanding of depression evolves over the century, the memelky cabrera commonly was cause, melancholy, enlightenment it was believed to be inherited unchangeable weakness of temp rament. >> sigmund freud, today at its broadest level question pegs, depression is viewed as a state of disturbed brain responses to internal and external signals of stress. the right of william sty rum once wrote of his experience with depression, the pain is unrelenting and what makes the condition intolerable is the fore knowledge no remedy will come, not i in in a day, an hou, a day or a month. he chronicled his own the battle of depression with 2001 national award winning book, the noonday demon, an atlas of depression. he is also a lecturer in psychiatrist at cornell medical

college and shares his story and his insight into the disease. also joining me tonight a remarkable group of scientists, peter whybrow is director of the jane and neural science and human behavior and professor of the david again never school of medicine. >> frederick good win is at george washington university and direct orr the medical progress in seat. hell 11, helen mayberg is radiology in the chair in psychiatrist, in therapeutics at emory university and my cohost is dr. eric kandel, se a nobel laureate, professor at the university and a howard hughes medical investigator and begin as usual with dr. kandel. >> thank you, charlie. >> >> rose: what should we be doing? >> we should think about how we got to where we are. you began that very wonderfully, at the beginning of the 20th century, the founder of modern

psychiatry divided the major psychiatric illnesses, the psychotic illnesses into two groups, disorders of thought and cognition and disorders of mood. disorders of cognition equaled dementia, we call it schizophrenia and discussed that, a couple of programs ago. the disorders of mood, we now realize depressions and this is what we are going to discuss today, depression comes in two forms, uni polar depression and bipolar depression. uni polar depression is, as you indicated was appreciated as early as hypocrites i the fifth century bc he thought all diseases of the body were due to imbalance between the four humors, they didn't think of diseases as being organ specific but -- >> blood, phlegm, yellow bile

and black bile and depression was an excess of black bile, in fact, melancholy is a greek word for black bile, the first good clinical description of depression came with a very famous 17th century psycho analyst by the name of william shakespeare. your friend. he had hamlet say, hour wary, stale, flat and unprofitable seems to me all the uses of the world. and as you pointed out the character features depression which we are going to hear about as a sense of hopelessness, helplessness, low self-esteem, an unending poor mood, a sadness, relentless day in and day out, associated with deep psychic pain. this is very common disorders worldwide, about five percent of the population suffer from deprotection at one time or another and the united states it is the major disability in

people between 15 and 45 years of age. and it is also associated with sort of a loss of interest of what is going on in the world, it is a very devastating disease, bipolar depression involves in addition to the depressive he episodes, episode of mania. and these are almost a mirror image of depression, a feeling of you can accomplish anything, euphoria, excessive talking, feeling that they are sexually very powerful and often become sexually very active, no need for sleep, and sometimes really engaging in risky behavior, they gets into all sorts of difficulties. about 25 percent of people with uni polar depression also suffer from bipolar depression.

fortunately, we have been able to get .. various treatments of them. one of the most remarkable treatments came from larry burn this ime and i should introduce this as we saw in schizophrenia where a number of the drugs were introduced by accident designed for other purposes in drug that person i'm i'm, bernhime was initially used for tuberculosis, but this was, he was an ordinary, she was an extraordinary farm colonel gist, and she, pharmacologist, she .. discovered this enzyme, this inhibitor of the enzyme and moved to duke and became the main stay of the pharmacology department at duke university and had an extraordinary career. this drug was later picked up, a

particular strairnt of this, and used for tuberculosis, which was thought to be its target, and astute clinicians actually here in new york noticed that patients on tuberculosis were jump jumping around, most of the others were fatigued? what depressed, these people were happy and comfortable, and somebody got the idea let's try this in depression and turned out to be really quite effective, almost, as this was being another antidepressants came around which this is a good example and soon realized that both of these drugs have a common set of targets, they act in the modulator neurons of the brain, and this was not only an insight into the possible site of action but gave rise to a hypothesis of the nature of the

disease and people began to think of depression as being a depletion of these module transmitters and these drugs were designed to replenish the reservoir of these transmitter and the focus was to a large degree in serotonin thinking this was the most important component. >> john a day was the first one to introduce a treatment for mania, john caday, the greek physician had tried to treat patients with mania with waivers he thought contained lithium and found that they were responsive to it, but this idea was dropped, experimented with rodents, and found that when he injected this into rodents, they became more lethargic and he wondered whether the manic patients wouldn't do do better if they slowed down a little bit and he introduced lithium in the

1970s and it turned out to be a very useful treatment for depression. in addition, throughout all of this period, people receiving psycho therapy, to see whether or not it could be helpful in depression, and really several major advances have occurred in psycho therapy and we will hear about that today. first of all, we now have evidence that psycho therapy is a biological treatment, in part through helen's work, we know that you can detect an abnormality in brain imaging in depressed stations and only if there is psycho therapy a reverse sal of that and that is very similar zero to what you see with certain serotonin uptake inhibility tors, number one, number two we also learned how to combine pharmacological treatments and psycho therapy and how different forms of psycho therapy might be particularly effective, so we are in for a fantastic

discussion of depression and mania. >> rose: it is extraordinary to me because it is one sort of illness we know people, it touches so many lives, someone we know has someone they know, or they love or their family. peter, help us understand what it looks like and feels like from the patient's point of view. >> well, as you mentioned at the very beginning, these are moods apart. they are not the normal sadness and sense of unwellness that we experience from time to time. they are an active anguish, i think -- >> rose: it is not your ordinary mood change. >> exactly. and so they are all the where all the goods of life seem to be diminished. that is william james spoke eloquently about that, probably following on from mr. shakespeare, but, in fact, that is what distinguishes them. so when people walk into the office, they usually have suffered these things for a

while, and they say, i don't know what this is. as you listen to them, you begin to realize that as a, as the constellation of symptoms, they can't think right, they can't think the way they used to. their decision making is not sharp, they miscue people, they can't quite understand what it is people are telling them socially, they feel they are being alienated by friends, when they are not. they can't give their own sense of emotional -- it is almost as if the emotional pendulum which goes back and forth every day for all of us has gotten stuck and so what also happens in that sticking is that you find that the usual housekeeping of the body is lost, you know, they sleep at the wrong times, they have all kinds of pain in terms of being able to eat. they don't want to eat. their there are sexual things are no longer of interest.

so all of these things tend to cluster together. i remember a patient, for example, who in london when i was a young physician, he was broad in by the police, he had been found sitting on the steps of the national academy, in trafalgar square chewing aspirin tablets at 4:00 in the morning, and he was intending to kill himself. he knew that. >> rose: the pain was so great. >> yes. he knew if he took enough aspirin he would die. he was a very prominent lawyer it turned out and he had episodes of depression before but this time he felt, my life is over. i have been poor to my family. i am not a good lawyer. i am a fake, and in fact his whole thinking which as a great trial lawyer he had been one of the great advocates, he had lost it. we brought him into the hospital. he -- we told him we were going to get him ect, six weeks later, after, of course ect he was back

practicing law. so the fact is that these are treatable illnesses but they are illnesses. the onus of the self, where all of the usual things we experience as an individual just dissipate, disappear. >> rose: andrew, take us there. >> well, i thought of myself as quite a resilient person and quite capable of rising to almost any occasion, and then in 1994, i found myself feeling strangely detached from what was happening in my life. i was publishing a novel, i always wanted to publish a novel and doing reasonably well and i didn't care about it and i got with friends and i thought, oh, why bother and i thought about doing anything else and i thought why bother after one thing after the next? there was a complete lack of interest in any of it and then as time went on, everything began to feel difficult, and i remember getting up and i would think, i should have lunch, but to have lunch i would have to get the food out of the refrigerator and

put it on a plate and cut it up and chew it and swallow it and it felt like the stations of the cross to go through all of that. >> rose: it was too much. >> it was just too much and i felt this sense of being overwhelmed all the time and get messages from people i loved on my answers machine instead of thinking how great to hear from those people i would think, what a lot of work it will be to call all of those people back. i would think, oh i should go take a southern and think well do i really have the emergency for that right now? so i felt myself in this strange, in this slow almost paralyzed state and that went on, and as it went on and began to get worse i began to think not only that i didn't feel like doing these things but they were totally overwhelming and ultimately quite terrifying to me, i thought oh, my god i have to get up and go to the corner and do something, one of the things i think people often don't say about depression but which is obviously true is when you are in it, you know that it is ridiculous, you think i have eaten lunch all my life, people mostly eat lunch it is not that

difficult, you in the state in which you simply can't do the ordinary things you previously had done, and then the anxiety sets in and anxietys of depresst tend to occur with it, and when the anxiety sets in, i once said to someone it was as though you are in the moment when you slip and trip but before you actually hit the ground, that feeling of out of control terror but instead of it la lasting for a split second it lasts day after day, week after week, you are just stuck in this feeling of being terrified of everything and not even knowing what it is you are terrified of, just a feeling of this relentless appalling fear and it got worse and worse for me and i found it harder and harder to do anything and i had both experiences which i think are now understood by, that something was sitting on top of me, there was something external to me that was creating all of these problems, and the sense that something had been removed from inside of me, i just was no longer the person i had been who had done all all of these other things i would look at pictures sitting around and

seemed they area they were of somebody else's life and i found myself in worse and worse share ishape and finally one day i woe up and i thought, i should call someone. i ai am not doing very well andi couldn't -- i looked at the telephone and the idea of reaching and picking up the telephone was so overwhelming to me and i lay there for four hours, i almost thought i had a stroke because it was all so difficult and finally the phone rang and it happened to be my father and i said something has gone horribly wrong and can you come down here and help me out. and it was devastating. and i am thinking, keeping with what peter just said i would often say the opposite of depression is not happiness but vitality, it was the vitality that was absolutely destroyed in me. i had no will to do anything. now, of course depression often leads to suicide, and i didn't ke any kind of an active suicide attempt, but that was because the idea of organize aring myself to do it seemed like more than i could manage, yes, absolutely and i think that if you could die as a passive

act rather than an active act the number of people who die from this illness would vastly escalate, and then when i finally did get treatment and a little more energy going i thought, i really would like to heal myself, it wasn't that i didn't believe i would get better, doctors said to me you will get better, it is i couldn't figure out how to get to the next second, the next day if they said you will get better in a few months they may have said there is redemption when you goat heaven, i thought i cannot tolerate it and that feeling of pain, of it just being so painful to be alive, and everything seeming so daunting, when i was in higher spirits i have gone skydiving and tell you at that point poe it was more frightening to get out of bed and go into the bathroom and take a shower than to jump out of a plane at high altitude, it was just terrifying and ifn tolerable and i thought if it doesn't -- i would have done anything to make it stop and taken any physical illness instead. i would have taken any other experience, it was the worst pain i have ever known.

>> rose: so how did you stop? >> eventually, i went to see a therapist, i got both pharmacological treatment and sty co therapy and the two of them ended up working well with each other, and i gradually emerged and like everyone else i thought well i am feeling a little better so now i can stop with all of this treatment, and then i got another depression. it is a cyclical illness and tends to occur and i got better and went over and over again before i finally realized i just need permanent help and permanent treatment. and once i allowed that, the feeling of relief that was attached to it was so incredible and the feeling of my life returning to me and i thought, oh right and i feel lucky because i had a nice enough life i knew what i was feeling was irrational and i think it is even harder if your life is a complete disaster and you start to feel these things to realize how the symptomatic and strange they are. but i think the thing i most emphasize is the physicality of

it, i almost forget when i am not depressed i think to myself oh well i had a rough day last week, and then it comes again, it is always there lying in wait and when it comes again, i think there is nothing i can do in the fails of this. it is the most, not only the most painful but in some ways the most powerful experience i have, as if my whole body has been destroyed. >> rose: when is the last time you felt this? >> the last time i had a really serious episode was in 2004. >> rose: so eight years ago? >> so it has been a while. i finally got really good treatment. >> and the diagnosis was? >> major depression. >> rose: major depression. >> yes. >> rose: how many forms are there of depression? >> well, you know, the best way to understand what we have been hearing is to look at it as a spectrum, on the unone end of the spectrum you mentioned normal depression we all have bad days or bad runs of days and grieve reaction, grief reek sun in is cross reaction and look what you described but the difference is after a couple of weeks people begin to reconnect

and you never get the empty spot filled but you are not depressed anymore. >> one of the differences between grief reek shuns and depression is that depression is endless, no matter what happens you -- with grief .. friends come to visit you and you can reach out, as you said week after week, i mean the biggest distinction between one end of the other is duration, week after week versus transient, the degree of symptoms, i mean if it was just about your mood and your thinking, that is one thing, if it is about your body, total body illness, sleep, appetite, everything you mentioned, then it is the other end of the spectrum, the pharmacological treatments are absolutely required in the more severe end of the spectrum, they also work in the middle of the spectrum but so does psycho therapy work. sometimes the combination works better than anything else. you mentioned suicide. depressed patients when they recover, you know, goñi about putting their life back

together. they go about putting their family relationships, and a lot of damage that occur and most depressed patients can, you know, get maybe 80 percent of what they had going for them back. but the one irreversible tragic out come is of course suicide, and 80 percent of all suicides are explained by clinical depression, and the suicide rate is a very interesting paradox that women get depression twice as often as men but men kill themselves three times or four times more often than women. so if you put those two together it is like an eight fold difference in terms of, you know, men with depression are that much more likely to kill themselves than women and the reason for that is that the most successful methods of suicide are the aggressive violent ones, guns, jumping off bridges, throwing yourself naah subway and the other ones is -- so what suicide is, is an intersection of depression and aggression, and that, of course, is the

ultimate point about getting effective treatment. >> rose: so how do you distinguish between uni polar and bipolar? >> both depressions are recurrent, the most recurrent form of depression is bipolar, that is, depressive episodes, alternating with manic or hypomanic episodes, you mentioned how pleasant mania might seem to be, yes, it is pleasant, in its milder forms, you know, the increased speed of thinking, increased sense of creativity, increased sense of pleasure. then in the middle it is not so good when you estimate everything is coming up roses and whatever you do will be all right and then you begin to get in trouble. but at the severe end of main, i can't it is a terribly disfor rick and painful .. place to be and the notion that that is a pleasant state is really not true. >> rose: but it is apparently so amazing about bipolar disease is that some patient whose apparently don't want to be treated for the depression, because coming out of the

depression into the mania is so fantastic, it is addictive. >> rose: i was going to say what goes up comes down and what comes down does not necessarily come up. >> what mode does genetics play. >> it is the most important predisposing factor, bipolar is estimated to be about 80 percent of the variances is predictable by family history and genetics, and these are, where they do identical twins reared apart which is the best way to separate nature from nurture, next to autism, it is the, bipolar is the most genetic illness in psychiatry, it still requires a trigger and once it is triggered like the first episode in bipolar and this might occur when you are 17 or 18, once it is triggered the brain is changed and you follow that patient over several episodes, by the third or fourth episode it doesn't need much of a trigger at all, it seems to have taken on a life of its own and then there is high think

recurrent you any polar, they don't have depression but a need for long-term treatment, preventative treatment and focus a lot on treating the actual depression, that is in front of us but perhaps there is much more importance in the long run about adequate ways to prevent something. and there, is you know discussion now about could you detect this stuff really early and perhaps treat a child before they have their first episode is one of th the emerging areas of research. >> rose: peter, talk about newer biology of de, neurobiologist, neurobiology of depression. >> so suddenly we had drugs that could actually perturb the central nervous system and make the individual feel better, not instantaneously like cocaine and amphetamines but overtime they would feel better, and this became one of the things that was identified as the

pharmacologic bridge, it was thought that in was taking us from a behavior to an understanding of brain, and i was at that time working in england at the medical research counsel and we are very interested in serotonin that you can see here, but in america, folks were very interesting in norepinephrine one of the other long tracks these were .. very interesting interesting part of the brain, they start in the ancient brain in the brain stem and they go like a tree over the frontal lobe and the ko cortex, which is the very human part of us, of course. so began to realize that the pathways were working together, and most of the early drugs actually influenced all of these path ways, and later it was realized that this was a focus of modulation, which was organized around the sin naps

and that was very exciting because suddenly psychiatry had been out there .. talking for years and lying on couches and things, suddenly had, they could join the physicians again, so the early drugs were not extraordinary because they had lots of side effects, some people had a dry mouth and they didn't feel well, but they felt better. >> sexual dysfunctions and so on, and along came refinements because of advances in the pharmacologic industry and they realized this is a potential market and they refined these drugs and the ssri's, serotonin reuptake inhibitor came out, in the late eighties, early 90s and that was a great boost, because the side effects were far better. but what we increasingly recognized, i think, and technology was advancing along the way, we were beginning to be able to image the brain, and so we would be able to see the

anguish going on inside somebody's head in terms of blood flow, which areas were active, we know that the anatomy because that was also progressing is different for these parts, that the frontal lobes control some of the limb bic structures, this anatomy had all been advances during the same time, when i was in medical school we had no idea what the frontal lobes did basically so if you put that together it was a systems problem and that was one of the great advances which i think then brought even neurologists in to talk to us about depression. >> rose: helen, depression on a biological basis, and a neural circuit, a neural circuits. >> well i think what he everyone has been talking up to now is the idea this is in the brain and for phrenology the question is where in the brain, and real estate counts, you have to actually know which part of the brain does what. it isn't a big bowl of soup, add serotonin and stir which was really the concept that moving from psycho therapy to pharmacology embraced, moving

into the brain was the first step, but the issue is, how to dissect the symptoms, the syndromes into the component parts because while it is an involvement of many parts of the brain, its, it is involvement of specific parts of the brain, and the way we approached that was we couldn't do it as we usually did in neurology by dissecting the brain after someone died like you would after they had a stroke and say they couldn't move their arm or they had a language disturbance. there weren't large lesions in the brain with people with depression so we had to take advantage of functional imaging methods i know you have talk about on other episodes. >> rose: right. >> could actually literally say when you are depressed what areas of the brain aren't working properly? take a very simple-minded point of view. this is really a wonderful point, because many people don't appreciate this. but one of the ways pathologist distinguish between psychiatric

and neurological illnesses in let's say 1,800, 1900s they would take patient whose died of neurological illness, psychiatric and cut the brains, if they saw a large hole in it they knew it was a neurological disease because most neurological disease caused significant localized changed. >> if you could cut it and see it, it was neurology, if not, it was psychiatry. you cut the brain and didn't see anything obvious because as we have now learned these are more subtle changes, then it was a psychiatric disorder and it wasn't until functional imaging came along, this is why helen's work is so extraordinary, that you could really defeign a neural circuit involved in the disorder by using imaging. >> i mean it is really remarkable, you know, fluid, warneke, alzheimer's, everyone knew these were brain disorders and all cutting brains way back and just couldn't find anything and needed other theories to

accommodate what they knew to be true, and this is the remarkable issue about the time we live in, we have tools to test what we know to be true. fluid knew all of the things he was dealing with had a biological basis and tried to develop a model to deal them, and it was trivial he didn't publish it in his lifetime and he knew one day biology would come along and give you insight into it. so what people discovered was that it wasn't just one area of the brain, just like the syndrome has problem with different symptoms, multiple areas of the brain that weren't functioning normally, some were over active, some underactive, different combinations in different patients but there started to be a pattern and there started to be the nodes in what would become a pulteive network that was involved in major depression, what are the big areas? the ringleader as the data has evolved overtime, is this area 25, the sub -- it is

an area deep in the frontal lobe, and it seems to always show itself whenever there is an intense negative experience .. area 25 is the negative mood regulator, but it is also associated with areas like the mend la, the prime .. hub for mediating all stress responses. >> emotional responses. >> emotional responses, actually anything novel gets processed originally through the amen does la. >> they have an .. intimate relationship with one another, other area that are important regulate drive, like the hypothalamus, this is the core, many nuclei are involved in sweet, appetite, libido, a direct ling between area 20 give and the hypothalamus and that and the mendula, and memory context is there and when one thinks about what happens when an event happens in your

environment, it is immediately processed by the amendula, area 25 and that area have a discussion about it, the campus comes on line to kind of say is this familiar, have i been there the before to provide con text and a whole cascade of the events will go on to respond to those stimuli, not thought about by your prefrontal cortex, the area of the brain that really at the end of the day that will have to synthesize saul of, all of the information and decide what you are going to do about it and it is the cross talk, this choreography if you will which is how emotion and thinking help us to plan our day, and respond to the world around us in a functional and healthy way. >> you see, i think, what is happening here, is that all of the information is beginning to come together and make some sense, so that constellation that helen just spoke of becomes the infrastructure, the anatomic infrastructure through which we

can understand the illness, but more than that, which helen has done a lot of work on, is that the connections among those various centers are very important. the brain is not a single organ. it is a whole series of sub centers, it is like a great city, you know, when you put somebody's head in a machine and look at what is happening to the blood flow, it is like flying over los angeles or new york at night, you can see where everybody is having a good time and also see the people who are moving from street to street going with their cars back and forth. >> in fact, what ends up happening is through the use of imaging to actually see in real-time, where the points of disconnection are, and why, in fact, one has the sensation of the body that one can't place it, and one can do nothing about it because these emotional systems in the circuit are literally disconnected from the thinking brain, so you are actually highjacked by this emotional system -- >> and i think frequently there

is a problem, and i have encountered it in my own experience imagined in the experience of other people i interviewed as i wrote about depression, that people think that there is some kind of competition going on. is depression psychological in is it biological? and they also make the assumption once you have determined that, if it is psychological it coul should be treated in one way and if it is biological it should be treated in another way and it is a very neat and lovely way of describing things but in my experience actually the psychological and the biological are two different vocabularies that can be used for pa single set of phenomenon. >> and in the brain you can separate and understand why exactly .. andrew's experience can actually be translated to the level of the brain. >> it is so important to realize what an advance this is, the finding of a neural circuit in depression, we know schizophrenia also is in a single claltion of similarment have cognitive, negative symptoms as well as positive symptoms. we don't have anywhere near the

circuit diagram for schizophrenia that we now are beginning to have the depression, so it is a major advance, once you have a circuit like this, and you can image it, you can see to what degree different therapy is effective. >> i think that the -- i think there is an ultimate tendency among many people who suffer from depression to see a trigger. >> my trigger was my mother died or publishing a book, someone has something going on in their book when they become depressed and i often think if you have a difficult or traumatic experience and then you feel terrible, that a week later you feel marginally better even if you are feeling better it is probably grief and feeling better but you have this awful experience and you feel worse and a month you feel worse yet than that, then that indicates there is probably a depression that is taking on and people will often say, well i know i have this depression, but i have this terrible trauma, and even though it is a depression, i know where it came from and,

therefore, i am not going to address it and i say if you fall off a ladder and break your leg you know why you broke your leg but you still go get it set. >> how the brain is organized, one of the candidate for this is the body clock, which of course controls our arcadian sleep-wake cycle and the body clock has been the indicated in bipolar the illness going back two or three centuries and originally described. recently some genetic findings have shown a clock chain that is linked pretty close to the areas that have been identified as potential bipolar genes, so one of these organizing principles that peter referred to and that you referred to might be the body clock and as a clinic thinks i find managing sleep is perhaps the most important job of getting patients to have a normal sleep cycle. >> it is a lead symptom. >> the lead symptom is you can't sleep? >> well, the lead -- sleep tends to be the harbinger, you find that when sleep shortens, if you have bipolar illness, that is when the mania will fall, and

people who have uni polar depression, i don't know what andrew's depression was, sleep begins to fragment, their depression is coming on again. >> rose: andrew. >> i would sleep far too much and not be able to sleep at all for a week. it wasn't exactly -- there wasn't any particular direction. and now if i feel that there is a little bit of a depression coming on the first thing i do is to regularize my sleep, i have if i have to take a pill to get to sleep i do, even if i don't want to get up, i get up. >> this is good for everybody, period whether you have sleep or not, everything in terms of understanding the rhythm of your life. >> i mean, just on that, it just illustrates that these networks really mediate how emotion, activity, drive, planning, thinking, all work together, and this is why you can just regulate the system, even in healthy people. >> right. >> in depression, the system is broken, you are stuck. you can't self regulate. and that is the issue.

>> i would respond to both the idea of self regulation and the question you asked and one of the things that i think we haven't yet been able to fully chart is the relationship between these disorders and personality. you have a personality, you have native qualities of character, which are going to make it easier or harder for you to deal with the experience of depression. the symptoms may be very similar but your ability to rise above them may be very different. >> character counts. >> yes, absolutely. >> and character counts in the brain and actually the systems are different in people of different characters, including those that link the genes that put you at risk for depression so the story is complicated but actually there is a cohive narrative that is emerging. >> and i think there is a real truth that there are people who go through these episodes and then they decide, that was unbelievably horrible and i have, i am managing it out and i will never think about it again and ironically those are the people that tend to get

depressed by depression over and over again in the attempt to push it away they have actually failed to incorporate it into a coherent sense of self. >> that is why psycho therapy can diminish relambs. >> people are able to say i would not have chose 7 this experience it was a horrific experience but there were some profound things to learn from it and it has given me a different understanding of who i am, those are the people in in my experience who actually, it is not that they would have another episode but they will be able to toll rail tolerate it a lot better when it comes. >> right. in fact this has one of the interesting testing grounds of the interaction between the two, and the usefulness of different kinds of sigh doe therapy. >> rose: are we learning that simply .. in is something you can manage but it is always with you, because there is a -- >> this is like diabetes. this is a lifelong disorder. you have to be aware of the fact you have this disorder. and andrew is a perfect example. he is very sensitive to his mood shifts. >> rose: you feel it coming open. >> i feel it coming on but also

take medication and i have been in psycho therapy for years. and i think i would say the medication, i mean the moment when i finally caved and went to see a psychopharmacology was a turnaround moment in my life, i realize in retrospect i had minor precursor depressive episodes before the first huge major depression, i said one of my symptoms was anxiety and he gave me san max to deal with the anxiety, it is not a great drug to use for the long time but it is incredible in that state and i remember feeling oh things are possible and i started on these medication medications and a couple of months later i thought oh right i am me again, this is who i am and the revelation was incredible. but then to incorporate the understanding of myself, still with this vulnerability into my day to day life, that really involved psycho therapy and i think if you don't have any insight into yourself, you aren't going to know how to manage it, you won't know what it means -- and you also have to come to terms with being someone who is reliant on some external bunch of pills to be able to

function, i mean, i find myself, when i travel, packing extra medication to take on my carry on bag because i think if the plane got highjacked i would be okay -- you have to have it all the time and it is a big adjustment to think that. and you frequently, i at least had a sense of real family, and an enormous stigma around it but owe seem okay do you really have to take all of that medication, so on and so forth it takes a lot to keep going with it, and you need to work with someone who can help you understand yourself and who can help you understand the syndrome as well. >> one of the things that charlie and i have been trying to do in this series is to reduce the stigma with it. what is wrong with recognizing that you have got a disorder and taking drugs for it? if god forbid you had kern would people say why are you taking those drugs for cancer? >> i will tell you a story on this one. i was at a conference a while ago, which was not about this topic and it was a weekend long conference and there were various people there, there was

a man and his wife that was there and on the first day of the conference he took me aside and said, you know, i have actually had to struggle with depression and i am i can taking antidepressants but my husband would never understand i wonder if you can give me advice and described the whole thing please don't talk about it with anyone and i gave her whatever insight i could. on understood the third day of this conference, her husband took me aside and said, my wife think i was less of a man than i knew this, they were taking the same medication and hiding it in two different places in the same bedroom. the communication in the, i thought communication in the marriage might be one of the issues. >> rose: i remember one of the can dumb est things i ever said and said many dumb things by the way, was when i said to my cardiac surgeon, you know, i really don't like to take pills. and notwithstanding how relevant it was in a sense for someone who had had a cardiac illness, you know, it was essential, and that if to wake up he sort of said wake up to the 21st

century. >> that is a perfect example, and also the diabetes am write is perfect because you have to regularize your life after having recognized that you have a cardiovascular problem or sky by, diabetes so if you ate cream cake it doesn't matter how many drugs you take if you have diabetes you won't do well so the diet is then equivalent to what i think andrew is saying in terms of him having to taken the psycho therapeutic understanding to understand himself and create his own diet if you will for his life. >> what is the velocity of understanding about depression? >> are we on a plateau or learning new things every day? >> oh i think we are moving -- >> rose: has the imaging taken us to places -- >> we have never been before. >> we have learned from imaging it has provided a template to think about all of these things, you can test to see whether there is a change when someone takes a medication, what part of the circuit changes. what is the difference between getting better when you take medicine versus not? you can

see how the system is responsibilities receive to the treatment. you can, you can compare drug and psycho therapy and realize they have certain areas of the brain they effect commonly, they have other areas that are complementary that help us to understand why each one may get certain people better, but in combination people do better than either alone. we equally have now moved to the point to realize that there are some people, not like andrew's example, that actually can get well only with psycho therapy, and don't require drugs, but other people who actually do require a drug and can benefit also from psycho therapy. and we can actually are now learning that at the level of the brain with the brain scans in this .. circuit that actually there are biomarkers that say if you don't get psycho therapy you will not get better on drug, and alternatively, you may want psycho therapy but if you don't drug you are not going to get well. so we are actually learning that by having this circuit model,

having the data, having access and having involvement of patients that are systematically studied, we can actually pars the circuit, understand the patterns and understand adaptation of how to facilitate the brain getting back to an equilibrium state and that kind of work has only been enabled by these advanced technologies. >> there are also two very important things that i think are emerging from the study of depression. and also, all of them have to do with public perception. and maybe fred would speak to this, but one is, there is the impression among some people that the antidepressants are no more effective than placebo which is simply wrong in severely depressed patients, number one, and number 2, because psycho analysis .. has sort of fallen out of favor because it is long, it is expensive, and it is noter the

blue empirically based people now are concerned with the psycho therapy which is a shorter mode of treatment and some of it is really not based on -- necessarily is effective. but what has happened recently is people have done studies of outcome in a more rigorous way, particularly for cognitive therapy and starting to do this insight psycho therapy and getting better insight into what kind of psycho therapy works and peter can speak to them, the advantages of insight versus cognitive behavior therapy so depression has given us really a sort of landmark set of problems in order to explore the efficacy of treatment and to understand it and one of the mysteries, for example, which we still don't understand is, if you give someone anti-depressant and they respond brilliantly to it, and don't respond immediately, but respond within two or three days, take ten days to two weeks to begin to see an effect, why is that so? so this is something we can now begin to

explore. >> i will go back to your velocity question. all of the science we are talking about is a wonderful velocity but translating that into the real world of helping patients, that is the best of times, worst of times, the worst of times is the pharmacology air is moving out into the brain area and intet getting incredibly expensive, some, i think, excessive demonization of the industry, they don't want to work with academia anymore, because academics get stigmatized for it so you have this proliferation of fantastic science but looking down the road all the leaders in the field are saying wait a minute how will we get these fantastic discoveries translated into things that can go for patients? >> i think the pharmaceutical industry i is that has move as e have in this round table discussion from the sin naps to is system .. >> right they are finding it

economically difficult to do it. >> and particularly if you want to get a focus like you are saying, you know, there might be a biomarker. >> one of the other disconnects between where we are in terms of development, given the science, is that while we have many treatments that match to the right patients are incredibly effective, we shouldn't hide the fact that for many patients, what we have to offer, the medication so, the day the medication stops working the psycho therapy is ineffective or what worked for someone stops working and the issue is, it is nonot as simple as we are reducg it down, because for many people, they stop responding and they become treatment resistant. >> the models in the pharmaceutical industry have been around a hypothesis that is exhausted and the issue is what is next to do? and i think what we have learned from the network approach, that if you can

understand how what we have works, but make some strategic decisions about the network itself and understand the nuances of the network, one can actually have some paradigm shifts in thinking about the treatment it civil itself. >> the .. problem with brain stimulation it basically said we are going to target strategically the area that we think is the ringleader and if we can change the activity there, irrespective of what chemicals the system may or may not have, but if we can modulate it directly electrically as we do in parkinson's disease, make we can get the system unstuck and then the rest of the system will reequilibrate, as it turned out that was a reasonable hypothesis and people who have stopped responding to any treatment, electrical voltage therapy included by strategically targeting that area, you can release them from these shackles of this sustained, pervasive state and

then one can engage them in the recovery process with psycho therapy, and as long as the rhythm of the brain is maintained through the continued stimulation, they stay well and don't relaps, but should the .. battery be depleted or turn it on with medication, they will get the ginled -- they will relaps. so even with something where we think we are being very strategic, it doesn't cure whatever is broken .. but it puts the brain back into a rhythm that allows it to move on and recover. and we need to understand what we exactly did because that will help us and lead us to a development of different classes of drugs that we aren't in a position to think about yet. >> thank you. >> if you follow up on that, i think, charlie, the fact is that all of our treatments actually perturb this system in some way, you know, the antidepressants actually sit there in the brain, and accommodates to ec.

ect per tecials the brain so the idea you have to get that system moving again towards equilibrium and i think in some ways what helen is talking about now makes it much more specific and it means that people can then become their own equilibrate tors by understanding these things, unfortunately it is not just in psychiatry but generally people are very ignorant about their own healthcare. they don't really take care of themselves very well, and although we have enormous knowledge object there, some studies shows 50 or 60 percent of the population actually donds they are trying to manage for themselves. >> rose: i agree. thank you, peter, great to have you here, thank you, andrew, thank you, fred, thank you, helen. eric you have done it again. tell they what is up next episode. >> we have another fascinating topic. so it turns out that there seems to be an underlying common pathological mechanism to alzheimer's disease, to frontal

temporal demeant i can't, to parkinson's disease, these degenerative sees of the nervous system. .. they are all due to protein unfolding and these abnormal proteins forming a gas and the aggregates spread from one cell to another .. so we will have people that specialize in parkinson's disease and huntington's disease and sam prusner who discovered this mechanism will all be here to describe this common theme that is emerging that pulls together all of the degenerative diseases of the brain. >> rose: thank you very much, eric, 22ed to see you again. for those who have been listening to this and those of you who would like to have more information, clearly you will see at the beginning respective institutional affiliations of the people who have been a part of here and also go to my web site and see a rebroadcast of this clearly when you have a

stigma in any way attached, it is a crying out for new information, and understanding information, so that you have an awareness that, a, you are not alone and b, that you should not consider yourself so and that other people have experienced it and some sense of talking to professionals can make a real difference for you, because the really ologist at this of change is remarkable. thank you for joining us. see you next time. captioning sponsored by rose communications captioned by media access group at wgbh access.wgbh.org