>> rose: welcome to our program. tonight a special edition of the charlie rose brain series year two. >> we focus on depression. >> it was as though you were in that moment when you slip and trip but before you actually hit the ground, that feeling of out of control terror, but lasting for, instead of last fog a split second it lasts day after day, week after week you are stuck in this area of feeling terrified of everything and not knowing what you are terrified of. >> this is a 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 in people between 15 and 45 years of age.

>> rose: episode 7 of the charlie rose brain series, understood written by the simons foundation, coming up. >> the charlie rose brain series is about the most exciting scientific journey of our time, understanding the brain. it is a series is made possible by a grant from the simons foundation, their mission is to advance the frontiers of research in the basic sciences and mathematics. fundgtç for charlie rose was provided by the following.

durable funding provided by these funders. >> and by bloomberg, a provider of multimedia news and information services worldwide. captioning sponsored by rose communications from our studios in new york city, this is charlie rose. rose. >> tonight we will continue our study of the human brain, examining one of the most widespread disorder, 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 of the united states will suffer from a form of depression during any year. the lifetime risk may six seed 15 percent. >> our understanding of depression has evolved over the centuries, hippocrates believed the mel commonly as it was known was caused by an excess of black bile in the spleen, during the age of enlightenment depression was believed to be an inherited unchangeable weakness of tell rarment, in the .. early 16 century, freud described it as aggrieve response to loss, today at the broadest level of depression is viewed as a state of disturbed brain responses to internal and external signals of stress. the 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 in a day, an hour, a month, or a minute. andrew solomon chronicled his

own battle with depression in his 2001 award winning book, the noonday demon, an atlas of depression. he is also a lecturer in psychiatry and joins me this evening to share his story an insight into the disease. also joining me today are remarkable group of scientists, peter whybrow is director of the jaind an institute for neuroscience and human behavior and a professor of the david give never school of medicine at ucla, goodwin is clinical professor of psychiatry as george washington university and helen mayberg is professor of psychiatry and neurology in radiology and a chair in psychiatry and nea therapeutics. >> and eric kandel, he is a nobel laureate, professor at columbia university and 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, andou y began that very wonderfully at the beginning of the 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 he called dementia precox and now call 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. unipolar and bipolar depression. >> unipolar depression was appreciated as early at hippocrates in the fifth century bc, he thought that all diseases of the body were due to

imbalance between the four humors they didn't think of diseases as being organ specific but mind specific. 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 really sort of 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 stale, how flat seem all the uses in the world and as you pointed tout characters the features of deprotection which you are going to hear about, a sense of hopelessness, helplessness, low self-esteem, 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 depression 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 and a very devastating disease. bipolar depression involves in addition to the depressive 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 to sleep, and sometimes really engaging in risky behavior that gets them into all sorts of

difficulties. about 25 percent of people with union polar depression suffer from bipolar depression, fortunately we have been able to get various treatments of that, one of the most remarkable beginnings in treatment came from larry bernheim and i should introduce this by saying as we saw in schizophrenia, where a number of the drugs were introduced by accident, designed for other purposes, this drug that bernheim actually discovered, an inhibitor was initially used for tub for due w sister, she trained in england and cambridge and he is a graduate student .. in 1928, discovered this enzyme, this inhibitive 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, used for tuberculosis, it was thought to be its target. and here in new york astute physicians noticed they were jumping around, most of the other tuberculosis patients are fatigued and some what depressed and these people were happy and comfortable and somebody got the idea net -- let's try this in depression and it turned out to be quite effective. as this is being tried another group of these drugs came along and they soon realized both of these drugs have a common set of targets. they act on the modulatory neurons of the brain that affect

the neurons and this was not only an insight into the possible the action but it gave rise to a hypothesis about the nature of the disease and people began to think of depression as being a depletion of these modulatory transmitters and these drugs were design to punish the reservoir modulatory transmitters after and after a while the focus was on serotonin thinking this was the most important component. kaday was the first to introduce a treatment for mania. the greek physician had tried to treat patients with mania, with waivers, wafers that had lithium and found they were responsive to it, and this drug came along and experimented with rodents and found when he injected this into rodents they became more

lethargic and wondered whether manic patients wouldn't be better if they were a little more lethargic and slowed down a little bit and introduced lithium in the 1970's and it turned out to be a very useful treatment for depression. in addition, throughout all of this period, people who are receiving psychotherapy to see whether or not it could be helpful in depression, and really several major advances have occurred in psychotherapy we will hear about today. first of all, we now have evidence that psychotherapy is a biological treatment in part through helen's work, we know that you can detect an abnormality in brain imaging and if and only if there is a response is to psychotherapy there is improvement of that and what you see with certain serotonin uptake inhibit tors. number 2, number 2 we learned

how to combine pharmacological treatments and psychotherapy and how different forms of psychotherapy might be particularly affective so we are in for a fantastic discussion in the area of mania. >> rose: this is extraordinary to me. because it is one sort of illness that we know people, it touches so many lives, it is 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 patients points of view. >> well, as you mentioned at the very beginning, these are moods apart, they are not the normal sadness and sense of unwellness we experience from time to time. they are an active anguish, i think -- >> rose: it is in the your ordinary mood change, and so they are all the goods of life seem to somehow be diminished, it 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, it is a constellation of symptoms here and they can't think right, they can't think the way they used to. their decision making is obtunded, they miscue people, they can't quite understand what it is that people are telling them socially. they feel that they are being alienated by friend when they are not. they can't give their own sense of emotional -- it is almost as if the emotional pendulum that goes back and forth every, every day for all of us has got stuck. 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 sorts of pain in terms of being able to eat. they don't want to eat. 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, he was brought in by the police and found sitting on the steps of the national academy, in trafalgar square chewing aspirin tablets at 4:00 in the morning and intending to kill himself,. >> 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 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 streaks, he had lost

it. we brought him into the hospital. he -- we told him we were going to get him set, six weeks later he was back practicing law. so the fact is that these are treatable illnesses but they are illnesses. the self, where all of the usual things that we experience as an individual just dissipate, disappear, and. >> rose: andrew, take us there. >> well, i thought of myself as a resilient person and quite capable of trying to any occasion and then in about 1994, i found myself feeling strangely detached from what was happening in my life. i was publish ago no. and i always wanted to publish a novel and it did reasonably well and i didn't care about it. and i had friend and i thought why bother and i thought about doing everything else and i thought why bother about one thing after the next. there is just a complete lack of interest in any of that. and then as time went on,

everything began to feel difficult and i remember getting up and i would think, i should have lunch, let's have lunch and 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: 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 think how to great to hear from these people i would think what a lot of work it will be to call all of those people back and i would think oh i should go take a shower and think, do i really have the energy for that right now so i felt myself in this strange, this slow to almost paralyzed state, and that went on and as it went on and began to get worse, i began to think not only i didn't feel like doing these things but that 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.

and 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, i think i have eat ten lunch all my life, most people eat lunch and do fine with it, it is not that difficult but you are in a state you can't do the ordinarily things you have previously done and then the anxiety sets in and anxiety is one of the components of depression. it tends to occur with it, and when the anxiety -- i once said to somebody 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 last fog a split second it lasts day after day, week after week and just stuck in this feeling of beinger the tied of everything and not knowing what you are terrified of. it is just, it is just a feeling of relentless alabama appalling fear and 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 both a sense that something was sitting on top of me. there was something external to

me that was creating all of these problems, and the sense something had been removed from inside of me that i just was no longer the person i had been who had done all of these other things and look at pictures i had sitting around and looked like somebody else's life and i found myself in worse and worse shape and finally one day i woke up and i thought, i should call someone, i am not doing very well and i -- i 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 and 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, manager has gone horribly wrong and can you come down here and help me out. and it was -- it was devastating, and i think in keeping with what peter just said i often say that the opposite of depression is not happiness but vitality and 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

make any kind of an active suicide attempt but that was because the idea of organizing myself to do it seems like. >> rose: it was too much to manage. >> absolutely and i think if you could die as a passive act rather than latent act the number of people who die from this illness would strapsly escalate, and then when i fine mhe 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 was that i couldn't find out how to get to the next second, the next day if they said you would get better in a few months they might as well stayed there is redemption when you g tote heaven. i thought i can't tolerate it and that feeling of pain of it just being so painful to be alive, and everything seeming so daunting, and when i am higher spirits, i will go skydiving, at that point it was more frightening to me to get out of bed and go into the bathroom and take a shower than it has been to jump out of a plane at high altitude, it was just terrifying

and intolerable and i thought if it doesn't -- i would have done anything to make it stop, i would have taken any physical ill imness and taken any other experience, it was the worst pain i have never known. >> rose: so how did you stop? >> eventually, i went to see a therapist and i got pharmacological treatment and sty co the therapy and the two f them ended up working well with each other, and i gradually emerged and like everything else i thought well i am feeling a little better and so now i can stop with all of this treatment, and then i got another depression, cyclical illness that tend to occur and got better for a little while and then another one and i went through it over and over and over again before i finally realized i just need permanent help and treatment and once i allowed that, the feeling of relieve that was attached to is to it was so incredible and my life returning to m and like, oh, right and i am lucky i have a good enough life i knew what i was feeling was irrational and i

think it is harder if your life is a complete disaster and feel these things to realize how symptomatic they are and how strange they are. but, i think the thing i most sympathize is theñi physicalityi almost forget when i am not depressioned i think, oh well i had a rough day last week and i remember what it is like 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 face of this. it is the most, not only the most painful but also in some ways the most powerful experience i have as my whole body has been destroyed. >> when was the last time you felt this. >> the last time i had a really serious episode was in 2004. >> rose: so eight years ago. >> it has been a while. i finally got really good treatment. >> rose: and the diagnosis was. >> major depression. >> rose: how many forms of depression are there? >> the best way to understand to disups this is as a spectrum. you mentioned normal depression and we all have bad days or the

bad runs of days and aggrieve reaction, grief reaction is cross-section natural and look like what you described but after a couple of weeks people reconnect and they don't get it over it, you never have the empty spot filled but you are not depressed anymore. >> he makes the .1 of the differences between grief reactions and depression is that depression, it is end less, no matter what happens. but when friends come to visit you -- >> yes you can reach out and week after week i mean the biggest distinction between one end of the duration is transient, the degree of symptoms, i mean if it is just about your mood and your thinking, that is one thing. if i it is about your body, totl body illness, sleep, appetite everything you are mentioning, then it is 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 psychotherapy work. sometimes a combination works better than anything else. you mentioned suicide. depressed patients when they recover you know go about putting their life back together and go about putting their family and relationship and a lot of damage that occurred and most depressioned patients can, you know, get maybe 80 percent of what they had going for them back, but the one irrelevant reversible tragic outcome 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 the two together it is an eight fold difference in terms of how -- 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 offer bridges,

throwing yourself into the subway, and the other is -- so what suicide is, it is an intersection of depression and aggression, and that is, of course, the ultimate point amount getting effective treatment. >> rose: so ho how do you distinguish between unipolar and bipolar. >> most depressions are recurrent .. the most recurrent form of depression is bipolar, that is depressive episodes, alternating with manic or hypomanic episode, now you mentioned how pleasant mania may seem to be, yes, it is pleasant and iand in its milder forms, te 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 in whatever you do, and everything you do is going to be all right and you begin to get in trouble but at the end of mania it is dysphoric and painful place to be and the notion that that is a mess santa state is really not

true. >> rose:. >> what is apparently so amazing about bipolar disease is that some patients who apparently don't want to be treated, 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 goes down but what goes down does not necessarily come up. that's the painful part. >> rose: what role does genetics play? >> genetics is the most important predisposing factor, particularly for the recurring illnesses, bipolar is 80 percent of the variance it is predictable by family history and genetics and this is where they do identical twins reared apart which is the best way to separate nature from nurture, next to autism it is the most, depression is the most genetic area of psychiatry, it requires a trigger and often once it is triggered like the first episode, in bipolar illness might occur when you are 17 or 18, once it is triggered the

brain is changed, and you follow that patient over several episeed, by the third or fourth episode it doesn't seem to be much of a trigger anymore at all, it seems to have taken on life of its own and then there is highly recurrent unipolar, they don't have mania but a need for long-term treatment, preventative treatment, and we 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. you know, there is discussion about could you detect this stuff really early and perhaps treat a child before they had their first episode is one of the emerging areas of research. >> and the discussion is going on. >> rose: peter talk about the neurobiology of depression for us. >> well, it has upon through several phases. one of the -- it started actually with the discoveries that eric spoke about earlier, and so suddenly we had drugs that could actually perturb the central nervous system, could 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 this 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 were very interested in serotonin which you can see here, but in america, folks were very interested in for ever 49 which is one of the other long tracks .. these were interesting parts of the brain communication system, sort of superhighways, they start in the age shunt brain down in the brain stem, and they arbor like a tree over the whole of the problem tall lobe and the cortex which is the very human part of us, of course. so we began to realize that the pathways were working together and most of the early drugs

actually influenced all of these pathways. and later it was realized that this was a focus of modulation which was organized around the synapse and that was very exciting, because suddenly psychiatry who had been out there talking for years and high 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, so 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 ba refinement because the farm logical industry, pharmacological industry realized this as a potential market and noticed the serotonin uptake inhibit tors, which came out in the late eighties, early 90s and 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 him bic structures, this .. anatomy had been advancing in the same time, in the medical school we had no idea what the frontal lobes did, in all honesty. >> it was a systems problem and that was one of the great advances which i think then brought even neurologists into talk to us about depression. >> rose: depression on a biological basis, helen, and a neurocircuits. >> i think what everybody is talking about is this is in the brainl and for neurology is question is where the brain, and real estate counts, you have to actually know which part of the

brain does what. it isn't a big bowl bowel of soup, add the serotonin and stir which was really the concept that moving from psychotherapy to pharmacology embraced, moving into the brain was the first step but the issue is, how did i assess the symptoms and syndromes into the component parts because while it is an involvement of many parts of the brain, its involvement of specific parts of the brain pa and the way we approach that was we couldn't do it as we usually did in neurology by dissecting the brain after someone died hike 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 brains in people with depression so instead we were able to take advantage of functional imaging methods, i know you have talked about on other episode, could actually literally say when you are depressioned, depressed what areas of the brain are not

working properly. this is a wonderful point, because many people don't appreciate this. but one of the ways pathologists 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 diseases cause significant localize it would anatomic changes. >> that was the old joy joke if you cut it and see it it was neurology and if you could treat it, it was psychology. >> but if you cut the brain and didn't see anything obviously obvious because as we now learn they are more subtle changes then it was this was a psyche i can't tridisorder and this is when imaging work came along you could really define a neurocircuit in a disorder by the use of imaging. >> it is really remarkable,

freud, warn question, alzheimer's, .. everyone knew knees brain disorders and cutting brains way back and just couldn't find anything and there are you need other theories to accommodate what they knew to be true and this is this is the remarkable the issue about the time we live in. we now have tools that allow us to test to know what we know to be true. >> all of the things he was dealing with had a biological basis and tried to develop a model to explain them and it was trivial he didn't publish it in his lifetime but one day he knew biology would come along and give you an insight into it. >> so what people discovered was that it wasn't just one area of the brain, just like the syndrome has problems with different symptoms that they were multiple areas of the brain that weren't functioning normally, some areas were over active and some were 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 putative network that

was involved in major depression. one of the big areas, the ringleader as the data has evolved over this time is this area 25, sub -- 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 .. all novel -- >> emotional responses. >> emotional responses, actually anything novel gets processed originally through the amendula (sp), and it has an intimate relationship with one another, other areas that are important regulate drive, like the hypothat will plus, this is the chore, hypothalamus, this is involved with sleep, appetite, libido, again, a direct ling to area 25 and the hypothalamus and

the hypothalamus and the amendula (sp) and when one thinks about what happens when an .. event happens in your environment, it is immediately processed by the mendula, area 25 and the amendula (sp) have a discussion about it and hit the campus comes on line to kind of say, is this familiar? have i been here before to provide context? and a whole cascade of 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 will have to synthesize all of the information and decide what you are going to do about it and it is this cross talk between these areas, 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, 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 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. when you put somebody's head into a machine and look at what is happening to their 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 see the people who are moving from street to street going with their cars back and forth. >> in fact, what end 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. >> rose:. >> and i think that frequently there is a problem and i have encountered it in my own experience and in the experience of other people i interviewed as i wrote about depression that people think 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, is it psychological then it should be treate 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 psyche lodgogical and biological are two electrocab layers that can be describing a certain type of phenomenon. >> and you can separate and understand in the brain why exactly andrew's experience can actually be translated at 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 knowñr schizophrenia also ist a single class of similar we have cognitive and 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 for depression so it is a major advance. once you have a circuit like this and you can image it uh you can see to what degree different therapy is affected. >> i think that the -- i think there is also a tendency among many people who suffer from depression to see a trigger, the trigger for he me was my mom died two years earlier and it was stressful to publish a book there is something going on in people's hives when they become distressed. when you have a difficult experience a week later you feel marginally better, it is probably grief and getting better but if you have in awful experience and a week later you feel worse and a month later you

feel worse there is probably a depression taking off and people will often say well i know i have had 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 always say if you fall off a ladder and break your leg you know why you broke your leg but you still go and get it fixed. >> how the brain is organized, one of the candidate for this is the body clock. which of course controls our or circadian sleep wake cycle and the body clock is perhaps a part of this. 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 peter referred to and you referred to might be the body clock and as a clinician i find managing sleep is programs the most important job, getting patients to have --

>> >> rose: you can't sleep. >> well, sleep tends to be the harbinger, you find that when sleep shortens, if you have bipolar illness that is when the mania will kid kick in and people with unipolar depression i am not sure what andrew's experience is, sleep fragments and depression is coming on again. >> i would sleep too much and not be able to sleep at all for a week. >> that's right. >> it wasn't exactly. it was not regulated and no particular direction and now if i feel that there is a little bit of a depression coming on the first thing i do is regularize my sleep if i have to take a pill to get to sleep i will, if i don't feel like getting up i will. >> but. >> rose: but senate good for everybody whether you have depression or not, understanding the rhythms of your life. >> and just on that, it just illustrates 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, in depression, the system is broken, you are stuck, you can't self regulate and that is the issue. >> i will respond to the idea of self regulation and to the question you asked and one of the things i think we haven't yell been able to fully chart is the relationship between these disorders and the personality. you have a personality, you have native qualities, and character which are going to make it easier or harder for you to deal with the experience of depression. the symptoms can be very similar but your ability to rise above them may be very different. >> yes, absolutely. >> and character counts in the brain and actually the systems are different in people of different characters, including those that are linked to genes that put you to risk at depression so the story is complicated but actually there is a cohesive 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 never going to think about it again and ironically those are the people who tend to be ambushed by depression over and over again, because in the attempt to push it away, they actually have failed to incorporate it into a coherent set of self. >> that is one way sty co therapy can diminish relapse. >> people who are actually able to say, okay i would not have chosen this experience it was a ohorrific experience but profoud things to learn from it and it has given me a different understanding of who i am, those are the people in my experience who actually, it is not that they won't have another episode but be able to tolerate ate lot better when it comes. >> right. in fact this has been one of the interesting testing grounds for the interaction between the two, and the usefulness of different kind of psychotherapy. >> rose: are we learning that simply in is something you can manage but it is always with you because there is -- this is like diabetes.

this is a hive long disorder. but you have to be aware of the packet that you have this disorder. andrew is a perfect example. he is very sensitive to his mood shifts the. >> rose: he feels it coming on? >> i feel it coming on and also i take medication and i have been in therapy for years and i think i would say that the medication, i mean the moment when i finally caved and went to see a psycho pharmacologist was a turn and moment in my life. >> i know i would have minor precursor depression symptoms and one of the symptoms was anxiety and gave me xanax to deal with the anxiety, it is not a great drug to use for a long time but wonderful when you are in that state and i thought oh, things are possible and started on these medications and a couple of month later i thought, oh, right, i am me again. this is who i am. i mean the revelation was incredible but then to incorporate the understanding of myself as with this vulnerability into my day to day life, that really involved psychotherapy and i think if you

don't have anyçó insight into yourself you aren't going to know thousand manage it and won't know how to have had -- 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 if the plane got highjacked at least 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 about it and enormous stigma about it and they say you really seem okay do you really need to take that medication? it really take takes a lot to go with it and you need someone that helps you understand yourself and 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 associated with it. >> right. >> what is wrong with recognizing that you have got a disorder and taking drugs for it. if god forbid you had companies

would somebody tell you why you are taking those drugs for cancer. >> rose:. >> i will tell you a funny story on this one. i had a conference and there were various people there, and a man and wife that were there on the first day of the conference she took me aside and said, i actually have had to struggle with depression and taking antidepressants but my husband would never understand, i wonder if you can give me advice and described the whole thing but please tonight talk about it with anyone and i gave her whatever insight i could on sunday the third day of this conference her husband took me aside and said, my wife would think i was less of a man if she knew this but i actually have had depression and taking the same medication and hide iing it in two different places in the same bedroom. and the communication in the marriage might be one of the issues but still. >> >> rose: i remember one to the dumbest things i ever said, and i have 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.

notwithstanding how relevant it was in a sense for someone who had a cardiac illness that it was essential and to wake up he sort of said to me, wake up to the 21st century. that is a perfect example, and also the diabetes analogy is perfect because you have to regularize your life after having recognized that you have a cardiovascular probable or diabetes so if you ate cream cakes it doesn't matter how many drugs you take if you have diabetes you are not going to do well so the diet is only equivalent to what i think andrew is saying in terms of him having taken the therapeutic opportunity to understand himself and create his own diet if you will for his life. >> what is the velocity of understanding about depression? >> are we in a plateau or learning new things every day? or what? >> has the imaging taken us to places -- >> we have never been before. we 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 somebody 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 responsive to the treatment. you can compare drug and sty co therapy and realize that certain areas of the brain, they affect commonly. they have other areas that are complimentary 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 no the point to realize that there are some people not like andrew's example, that actually can get well only with psychotherapy, and don't require drugs, but other people who actually do require drug and can benefit also from psychotherapy 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 psychotherapy you will not get better on drug and alternatively you may want sty co therapy but if you don't take 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 enable by these advanced technologies. >> there are also two very important things that i think are emerging from the study of depression and both 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 psychoanalysis is sort of fallen out of favor because it is long and spebls receive and it is not terribly empirically based people now are, who are concerned with sty co therapy which is a shorter mode of treatment and some of it the is really not based on insight effectively is effective but what happened recently people have done studies of outcome in a more rigorous way, especially for cognitive behavior and they have done this other sty co therapy so getting better insight into what kind of psychotherapy works and pete can speak to them, the advantage of insight over cognitive therapy. so this has given us a landmark set of problems in order to explore the efficacy of treatment as we understand it and one of the mysteries for example which we still don't understand is, if you give someone an anti-depressant and

respond brilliantly to it, and they don't respond immediately and don't 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. >> and go back to your gel loss at this question. >> rose: yes. >> all the sciencer the 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. >> rose: ah. why the worst of times? >> the pharmaceutical industry is moving pout of the brain area and getting incredibly expensive, there is some, i think, he he edges ses stiff demonization, they don't want to work with academia anymore because the, because they are stigmatized so have incredible proliferation of fantastic science but looking down the road, all of the leaders in the field are saying wait a minute how are we going to get these fantastic discoveries translated into things that can go for patients? >> i think it is part of the

pharmaceutical industry is nalt they have not moved as we had in in round table discussion from the -- >> they find it economically unfees to believe do it so the trials have gotten so long now and over a billion dollars. >> yes, it makes it very hard to do it. >> and particularly if you want to get a focus like you are saying, you know, there might be a biomarker. >> i think 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 patient are incredibly effective, we shouldn't hide the fact that for many patients what we have to offer they -- the medication stop workings and the psychotherapy is ineffective or actually, something that worked for someone stopped working and the issue is, it is not as simple as we are reducing it down because for many people, they stop responding and become treatment resistant. the models in the pharma

industry have been around the amino hypothesis and that has been exhausted and now the issue is what next to do and i think that what we have learned from the network approach, if you can understand how what we have works, but makes them strategic decisions about the network itself and understand the nuances of the network, one can actually have some paradigm shifts in thinking aboutphe treatment itself. >> you developed -- >> with el the issue with brain stimulation, it is basically, 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 the system may or may not have, but if we can modulate it the directly elect electricit elect electricitically like in park sons disease we can get it unstuck and the rest of the system may recalibrate. >> and those that have quit

responding to treatment to strategically targeting that area you can release them from the shackles of in sustained per i have five depressive state, and then one can engage them in the recovery process with psychotherapy, and as long as the rhythm of the brain is maintained through the continued stimulation, they stay well and don't relapse but should the battery be depleted or if you turn it on just like andrew described with medication they will get the dwindled -- they will relapse. 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 is going to help us and lead us to development of different classes of drugs that we aren't in a position to think about yet. >> rose: thank you. >> if you follow up on that, i think, charlie, the fact is that

all of our treatments actually perturb the system in some way. the anti-depressants actually sit there in the brain and then am come, accommodates to them, and, so the fact you have got 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 he quill libraries if you will by understanding these things .. it is not just in psychiatry but generally people are very ignorant about their own healthcare, he really don't take care of themselves very well and although we have enormous knowledge out there, some show 50 or 60 percent of the population actually don't understand even the illness they are trying to manage for themselves. >> rose: thank you, peter. thank you, andrew, thank you, fred, thank you, helen. eric. >> the court: done it again. tell me what is up next episode. >> we have another fascinating

topics. so it turns out that there seems to be and underlying common pathological mechanism, alzheimer's, the frontal tell proarl dementia, park sons disease, huntington disease, these degenerative diseases of the nervous system and all due to protein miss folding and these abnormal proteins forming aggregates, and the aggregates spread from one cell to another, so we are going to have people that specialize in parkinson's disease and huntington's disease and the person who discovered this mechanism, they will all be here to describe this common scene that is emerging that pulls together all of the desubsequent rative, degenerative areas of the brain. >> so 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 who have been part of here and also go to my web site and see, rebroad cpa's 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 other people have experienced it and some sense of talking to professionals can make a real difference for you, because of the velocity of change is remarkable. thank you for joining us. see you next time.

the charlie rose brain series is about the most exciting scientific journey of our time, understanding the brain. the series is 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 roshas been provided by theco o-ccala company, supporting this program -cnce 2002. and american interest. additional funding provided by these funders. and by bloomberg. a provider ofnd ed am news and information services

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