>> charlie: welcome to our program. tonight a charlie rose special edition. in the 9th episode of our brain series we look at the mentally illiterates brain. >> there are 1900 revolutionized the field. people had not known the number of different elnesses or one major elness and he broke it down into two major categories. there are orders of move and there are orders of thought. orders of mood he characterized depression and manic depressive illiteratesness. in orders of of thought he called schizophrenia. dimension, early phase of life. as you outlined, we have a very good understanding of his description of the nature of these diseases. >> charlie: the 9th episode of the charlie rose brain series underwritten by the simmons

foundation coming up. the most scientific journey of our time, understanding the brain. the series is made possible by a grant by the suom in the simmons foundations.

captioning sponsored by rose communications from our studios in new york city, this is charlie rose. >> charlie: tonight wecontinuex wonders of neuroscience. our subject this evening is mental illiteratesness. when our meant you processes go awry our mental difficulties can be self state, bipolar disorder and schizophrenia are some of the toughest known to human kind. they interfere with a patient's thoughts motivations and sense of self. society has stigma size of tiesed mental illness. this break through in understanding has improved the lives of those stricken and hoped the door for important research. with proper care. of thor able to lead productive

and fulfilling lives. tonight we'll meet two remarkable women who have risen in the top of their fields despite suffering from mental illiteratesness. kay redfield jamison is on bipolar disorder a disease she struggled with throughout her adult should hood she's at the johns hopkins university and mood disorder centers. elyn saks was diagnosed with skittlschizophrenia as a young . she publicly revealed her illiteratesness iillness in 200. she is a professor at the university of southern california and sacks institute of mental institute ethics at uca. joining mor three scientists who performed cutting edge research into the biology of mental illness. jeffrey leashman studied related psychotic disorders. he's a professor at columbia university and director of the new york state psychiatric institute. stevestephen warren his research

helped isolate the gene responsible for fragilelick syndrome. he's studying the basis of major psychiatric disorders. helen mayberg, her research uses scanning technology to isolate the brain regions involved in clinical depression. she's performed studies that illustrate the positive effects of deep brain stimulatioon depressed patients. once again mine cohost is dr. eric kandel. as you know he is a noble laureate, a professor at columbia university and a howard hughes medical investigator. so i am pleased to sort of begin this conversation in this sense for reasons you will tell us, this is a different episode of our series. >> we're speaking about major psychiatric disorders. as you outlined we're going to custody pression, manic depressive disorder also called bipolar disorder and

schizophrenia. we want to understand what we can do about them. these are as you indicated devastating disorders. they affect the way people think and feel and motivation. moreover one of the tragic aspects of these disorders is that they affect people early in their lives just as they're beginning to reach the peak of their productivity, the peak of their ability to enjoy themselves. schizophrenia typically begins in college or early 20's. these diseases often remain wi,h people for the rest of their life. therefore they're an extremely heavy burden for the patient and for the society at large. fortunately as you've indicated these diseases are treatable and we now have some clues as to

what optimizes treatment. early intervention and combination of sky co-therapy and drug therapy. >> charlie: you have a book here which is important because we constantly look ahead but at the same time we see the foundations for the kind of states we make. >> you're absolutely right. this is very important. the whole history is interesting. we've known about these illnesses since the greek physician in the 5th century not only spoke about depression and manic depressive psychosis but specifically indicated that these are medical illnesses. but this basic idea was lost on european medicine for the longest period of time. during the middle aches and even later in the -- middle ages and even later in the rendson period thought of as demonic disorders people possessed by the devil and moral degeneral cease.

people with disorders were put away from insane asylums away from the center of town and kept in chains so they don't move around. fortunately this situation was reversed in about 1800. the parent school of medicine began to really express a very modern view of medical science. and felipe pinell, a great french psychiatrist realized that psychiatric disorders as hippocrates has said are mental illnesses and he began to institute treatment at the beginning of psychotherapy with patients. from 1800 to 1900 no progress is made in understanding psychiatric disorders. one couldn't localize them specifically to the brain. so one didn't know is there one mental illness or are there many. that's when our mutual hero, emil came on the kcen% and his textbooks@ began to erge %n

1902 and continued until he died in 1926. he outlines for example in this book in his first three chapters he defines the fact that mental illness is not unitary. they affect two different processes mplegh. they affect mo mood on the one d and thinking on the other. difficult orders that affect moods, depression and manic depressive disorder. and it defines the disorders of thinking as schizophrenia, they call it dimension precox. they thought it was a deterioration of the cognitive processes in the brain early in life. precox. and we have some insight into the nature of these diseases' we know depression is an illiteratesness that involves mood which is associated with the nilling of forthlessness and inability to own joy life. nothing is all purveyive, nothing gives one pleasure. there's a feeling of helplessness often leading to thoughts of suicide and

tragedily to suicide attempts themselves. 25% of people that have depression also have. they feel fantastic at the beginning of the disease and ultimately this leads to grandiosity and frank scottish episodes. schizophrenia is a thought disorder that has three types of symptoms. positive, negative and cognitive. positive symptoms are characteristic of schizophrenia. it's the thought disorders, the delusions, the acting crazy. the social withdrawal, the lack of motivation and the cognitive disorders. are difficulty with organizing one life's and working with memory called short term memory. fortunately as you indicated, we now see people who have had effective treatment and have

productive lives and kay jamison and el i sacks despite they suffer from this disorder much of their life have rich personal lives, both of them involved the meaningful interpersonal relationships, marriage that is very satisfying to them and having spectacular academic careers. so there's tremendous hope for them. >> charlie: this is a remarkable thing. before we've had some of the leading and cutting edge scientist involved in neurology and brain science. here we have not only two who wo are engaged in important research. and are leaders in their field. they're also suffering, living with. >> this gives such hope to all of us. that you can have these devastating diseases and with appropriate therapy you can lead a meaningful rich life. >> charlie: we also found out a bit about the genetics in terms of the genetic basis. are they related biologically.

>> well that is still an act of discussion. we're going to hear from steve warren, we're going to hear from jeff leashman and helen mayberg the b biological underpinnings f these diseases and we know there are some genes that are different but it's beginning to emerge that some genes are shared by the two diseases. >> charlie: all right. this is one of the most interesting things we have done because in addition to those cutting edge science there's also this extraordinary person, personal testimony. we begin now with our case at the table. tell us about depression and bipolar disorder. >> well i think one of the thing that's really interesting about depression and bipolar disorders is they really affect not only mood but they affect energy and shape as well and thinking. so that people when they are depressed be very obsessive, think often of dying. but the mood is not one so much of sadness as it is really of

terrible hopelessness and deadness and disinterest in life. so all of the things that are ordinarily interesting in life to people become irrelevant basically. and people have trouble are sleeping, they have trouble getting to sleep they have trouble staying a sleep. it's an enormously all inclusive. people tend to think of depression as mood but it's really much much more than that. bipolar illness as eric said is in many ways the opposite. people very often have enormously high moods, feel better than they ever felt in their life so it's often very difficult to convince people who are manic, that they're sick because they feel great. so if you were talking to an 18 year old who is staying up all night full of energy, great ideas, or seemingly great ideas thinking fast and furious, you know, not very convincing they're totally sick. that's why the major clinical problems in threating these

illnesses is they do affect people when they're young and very unlikely to stay in treatment. >> can people often speak about psychic pain and depression. do you want to speak a little bit about that. >> one of the things is hardest to explain to anyone who has not been depressed is how isolating it is, how painful it is and that kind of pain just i'm convinced cannot be put into words, no matter how many great writers have tried to put those things into words. you cannot convey to anyone who you think about illnesses and terminal cancer where you think people would be thinking of dying and committing suicide. the suicide rate is really quite low. the people who really tend to kill themselves are people when they're depressed. it's a level of agony that is just astonishing. as i say, isolation in a sense of what's the moment. you don't feel human, you can't think, you can't feel, you can't love. >> charlie: some people reach out for suicide. >> absolutely.

>> charlie: when did you know? >> i certainly knew, i first sort of flew quite high as it were when i was about 17 and a senior in high school. i felt great, i felt no pain. i had a wonderful time but it wasn't that different from my usual. i was noticing that my trends were dropping like flies from exhaustion. it didn't seem -- what then happened is i crashed completely. i had never been depressed in my life, i never thought about suicide a day of my life, a minute of my different and all of a sudden i was incapable of remembering thinking, making sense of anything. and i just wanted to die. and i went around trying to figure out how i could die. i thought of death, i felt and i knew something was very seriously wrong. but at that time, i didn't put, nobody talked about depression, nobody talked about bipolar illness or manic depression.

so i didn't know what to do. so i did nothing. >> charlie: until? >> well i kept on that way up and down, up and down for another ten years and then i went flainlingly psychotic, i was hallucinating and delusional, manic spending a lot of money i didn't and have not wisely. and i, it was a medical emergency. so i was brought, you know, to care as it were. and i was very fortunate, i had terrific psychiatrist. she diagnosed what i had absolutely correctly immediately. and i responded very well to lithium. >> charlie: so the interesting thing is here you are in your field, one of those suffering. >> yes. there's nothing more motivating in life than merely dying from an illness which i did. because you want to know more. you really, you're a little

impatient with the pace of the field. yes, it's very 340e motivating. >> charlie: what do we know about the biology. >> well our approach to the biology of these major mental illnesses came from chemistry. and chemistry has dominated biological research for over 50 years. the major hypotheses with major depression was the bio genic hypotheses sort of the quarter low on serotonin or dopamine or nor epinephrin. that really was driven by observation of drugs that would alter those brain neurotransmitters. and then the recognition that replacing those neurotransmitters upping the level seemed to alleviate many symptoms. and that really created the foundation for hypotheses that these were deficits in these brain neurotransmitters. the problem was just filling up the tank, didn't keep you well. and that it really didn't accommodate the course of illness for many people.

but it did drive a lot of very very good neurobiology to understand the important role of serotonin in mood regulation. >> it was therapeutically very helpful for many people. >> that's the critical point. despite it didn't explain all the biology it has changed the lives of so many patients. and as a neurologist we're interested in not just what chemicals but where the chemicals act. like every other neurological disease where in this one, in the case of depression, you have a mood problem combined with slowness of movement, motor changes, a change in cognition. people are slow thinking, as well as disorganized but not like we're going to hear about psychosis as well as disregulation. your sleep is off, yorb your lio is off. this is about where in the brain they live. with the advent of neuroimaging

it was possible to test those kinds of hypotheses not so much with chemicals but what brain regions are doing what. and with tools like paws tron or pet scanning or functional magnetic imaging,fmri, we can literally map the brain in action and know exactly our brain areas that we ascribe these behaviors to. are they overactive, under active and we could start to map precisely how the brain circuits that mediate this disease are. >> ellen is ver el el elyn is ig because she was talking about the things like where is it located. she was the first person to find a b biological marker, an area n the brain that was active in depressed measures. do you want to discuss that. >> again we as well as many other investigators using imaging, we're really trying to take groups of people who had

classical symptoms and literally see what was wrong on our brains. are areas over active under active, one area or another area. we started to focus not just on one area but one area became very much critical. it's the area called the subclosal sing law. what we found is its activity is overactive in people when they're depressed. there's actually an effect in the frontal lobe, the thinking parts of brain that are under active. so there's almost a tug of war as the patients describe where there's psychic pain, a very active state of suffering that we think is really driven by this subclos subcolossal. >> she is going to show us things in schizophrenia as well but this was the first time someone had a a anatomical defet and you can use this to follow the treatment. >> charlie: tell me about schizophrenia and the clinical

syndrome of schizophrenia. >> as eric said schizophrenia is an illness that cause hallucinations and may include negative symptoms like apathy and withdrawal and cognitive impairment. when i tried to explain to other people, unlike mania which is fine, a psychotic episode is horrible. it's terrible, it's enormous pain. and i say it's like a waking nightmare with all the bizarre images and impossible things happening and the utter utter terror. only with a nightmare you sit up in bed and wake up and you can't just open your eyes and make is psychosis go away. that's what it feels like. foo are myself i will have permanent bizarre dilutions like i killed hundreds of thousands of people with my thoughts. occasional hallucinations, a big spider up the wall, santa claus coming out of a tv. who knows what that was about. i also have organized thinking. i had a break down at my first semester and i said to may classmates, are your legal cases

beingen filtrated. i don't believe in joints but they do hold your body together. so loosely associated words that when moot together don't really make sense. and that happens to me as well. i had been very fortunate except for the first two years of my illness i have not had negative symptoms. >> charlie: are there phases for this. >> there are different sort of what are called source indicators. there are some people might have one episode and be fine, some people are chronically psychotic, some people have even showed with interepisode being okay which is where i fit in. and-my own kind of with my illness i divide it into different phases. in the first phase the kind of prodromal phase where things started going wrong. i had my first kind of psychotic episode. i started walking home from school in the middle of the day and felt like the houses were communicating to me, they are sending messages. you were special, you were especially bad. look, see you must find. it was very scary. when i got to oxford i officially burnt down. at the second period, it started out looking like depression with

mild paranoid knees bu featuresn it went to a mood disorder and i was hospitalized the first year for a month, the second year for four months. by the second hospitalization i was having really frank psychotic thoughts like beams in the sky were putting thoughts in my head commanding me to do things like walk under in the hospital tunnels underneath the hospital and hurt myself. eventually they sent me to a psycho analysts. it's been enormously helpful. dure that phase i was not on medication. two things happened. my psychotic sill tums got worse. the positive symptoms got worse so i was living in the land of psychosis maybe 80% of the time. >> charlie: this is during the analysis it got worse. >> the negative symptoms got better. i started to be able to relate to people again and work again. my own theory is the mechanism of getting connected with the therapist, i started getting connected with other people too.

i had a break down in new haven. got on with another analyst and got on medication and had a ten year struggle whether i needed medication. foo are me my motto was the immediate medicine the less effective and the way i could prove i was the really illiterates was getting off medication. my analyst started saying you should just stay on the medication and get on with your life. eventually i tried that and this is the fourth phase. it's not like an off on switch but like a determine so i will have a thought like i killed people which i immediately dismissed. further awe lock the continuum i might spend two or three days in the land of psychosis and at the far end i would be crouching in a corner shaking for two weeks. that hasn't happened in decade. >> charlie: you wrote a book called the center can't hold.

>> yes. >> charlie: was it hard to come forward and be public this. >> i had a lot of people recommended i not do it including a psychiatrist and e mayor ticemeritus. it's awful awful you can't say it outloud. >> the two of you are articulate about your illness which makes the whole thing understandable to people. i would like something you both to address. you made the point that you couldn't stand being on lithium. if you liked it so much, why don't you take -- [laughter] >> this is not too long ago. he suggested my lithium. he said you know i've been treating you for decades, you haven't changed a bit.

it's not a struggle for me anymore because i nearly died. for most people, the idea -- bad side effects. you know. side effects are very impairing in your personal life. >> it's the narcissistic having an illness is hard to come to terms with. i don't want to use a crutch. if my leg was broken sure i would use a crutch. shouldn't i treat my neurotransmitters so kindly. >> charlie: steven warren what are the underlying of this. >> we know genetic plays a role by looking at family histories. schizophrenia occurs in 1% of the normal population but if you have a sibling with schizophrenia your risk goes up to 90%. even more striking is people who are identical twins they share

100% of their genome and the risk is now nearly 50%. what's important is it's not a hundredpercent like it is with simple genetic trait like cystic fibrosis where identical twins, both twins will have the same disorder. here half are discordant or don't share that disease. >> there are other factors playing a role like environmental factors. you see also looking at non-identical twins who are essentially just siblings but yet, they have a higher risk than siblings because they share an environment. we think of complex disease as now having contributions of genome as well as contributions to the environment. it's usually easier finding the genetic factors first and trying to sort out the environment. >> charlie: there are a lot of genes involved here. >> the problems, we know that it's not one gene, we don't know

quite how many genes but it's probably a handful of genes but learning in the last several years is that the brain unlike many other organs presents a mutational target. there are so many proteins that contribute to how the brain works. if you disrupt any one of them you might have a sill her outcome. so the different genes will lead to the same phenotype so it will get to a heart thing to narrow down. it's complicated because i think now with a new technologies that have emerged being able to sequence genomeses rather cheaply and other technologies gives us optimism that we'll be able to identify these genes in the future. >> charlie: take us to the biologist schizophrenia. >> elyn gave a beautiful description of the mental states of schizophrenia and steve just

told us that genes contribute to the risks. what it mains is that the seeds for the illness of schizophrenia are really zone during early development sewn in early development in the fetus. it affects not only brains but a select group of far ow neurocir, same things that exist in chips and stereo equipment come together and function. gene confers a certain degree of risk that an environment can either increase or maybe reduce. so famine or nutritional deficits during, to exposing the fetus during pregnancy when they have this effect, exposure of the fetus to infection like during influenza epidemics or taxic exposure if the mother does drugs or happens to have so type of toxic exposure can amplify this risk. during childhood, this vulnerability is pretty much dormant and individuals were

vulnerable to schizophreni these neurocircuits during adolescents, during young adulthood can begin to become dysfunctional. it occurs often times in the context of stress like when elyn was in school taking final exams, going to college, experiencing recreational drugs. maybe being drafted and going into the military. these stresses caused a dysfunction of these neurocircuits which result in the disregulation of the chemicals that elyn was referring to. but in this case involving dip mean. and this dope minuteergic tim lation becomes excessive and leads to the psychotic symptoms that elyn was experiencing, the hallucinations an delusions. one projects into the brain tell through the temporal lobe and

leads to the psychosis, and the other leads from the brain stem into the frontal cortex and think affects cognitive functioning and a third projects to the try actual and affects motivation, interest in things. so these three different pathways when the dopamine becomes disregulated under stress during the early adolescents, early adulthood in life lead to different clinical manifestations which come together to form the illness that kriplin diagnosed. all too often people don't come to treatment until after they've been sick for many years. and or they stop their medicine and they get sick again and when this happens and we have repeated insults to the brain and disregulated functioning, these neurocircuits treating dopamine, this leads to a progression and progression like somebody who has multiple strokes can lead to some decline

in which people are not able to recover at the same level. if you actually take brain scans, over time you can see the subtle but perceptible loss of gray matter which is e necking the illumination of these synaptic actions. >> charlie: you experience grief and depression. >> i got interested in grief and depression just because i had both. i mean i certainly had a lot of personal familiarity with depression in clinical. but my husband died about five or six, seven or eight years ago, yes, and i was struck then by the differences between grief and depression. even though they often get put together in the same category. but grief is something that all of us will experience, have already experienced, will experience. and depression is something that a lot of people will but not everyone. and the question is, what, why

do they exist and how are they different. and so i struggle with that to try and sort those things out. one of the thing that's most striking about grief is when you grief you feel alive. even though you may be desperately sad. and unhappy and missing and mourning. you femal feel alive. you don't feel unconnected with the world. you can easily reconnect with the world as friends come in and you go out in engagements. in fact grief comes and goes in very much waves that you, where you least expect it. but it's not an unremitting state and you don't die inside whereas with depression, depression is a deadened state that's unremitting. that doesn't respond to the world around you to the environment. you could be the best in the world or worst in the world and it doesn't have that much of an impact. it's an internal state. and one of the concerns that i

have along with a lot of my colleagues of course is you don't want to medicalize the human condition. you don't want to start putting people in psychotherapy or giving they medications because they're grieving. it's the human condition and it's part of what we learn. you move on from. >> charlie: make sure you distinguish between the two. >> that's right. >> yes. and 24569 you recognize when -- and you recognize actually the real challenge is to recognize when people have both. so you can treat the depression without people having to go through additional horrendous pain. you can treat that which is treatable and then leave to nature that which is nature. >> she wrote a mawiv marvelous k called nothing is the same. first of all richard her husband was a fantastic guy, major psychiatrist and the two of them had a great influence in each others lives which she de cryinged booth -- described

beautifully in the book. she described so beautifully the difference between this grief that comes and goes. it's not all the time. you can be moments of joy but you can't when you have the depression. >> it's quite interesting because you can actually study intense personal sadness and map it and get a signature of that. and you can actually do that same thing in people who are depressed. and actually look at the difference between being depressed and being depressed and situationally sad. and there are areas of the brain that are different and what struck me it was kind of a light bulb moment for me right now. the par that differs is an area of the frontal cortex that is upon for the self connectedness. and in depressed people when they're currently depressed and they get sad, that area of the brain doesn't come on as it does in healthy people who are experiencing episode or recollecting a sad event. >> if you look at how society

responds to you if you're depressed as opposed to when you're grieving. everyone can reach out to you or almost everyone unless they're complete creeps. i mean. but for the most part people really won't reach out to you if they know you have undergone a loss like a death. they will do so and those rituals will work for a while but not totally. society has involved ways through religion and friendships and so for to do that. in depression people avoid you because it is first of all depression's contagious. the mood is contraidges. and secondly they have a real sense that they can't connect. this cannot make a connection with you, you cannot make a connection with them. >> one of the interesting thing that emerges with both of you is that you had treatment fairly early in your disease, that was a very interesting combination of treatments and very effective in both of your cases. i wonder whether you could say on that. >> elyn and i have talked about this a lot.

i'm a huge admirer of everything she's done and her writing. one of the things we've talked about it's not just medication. i mean i'm completely beholden to medication. i would be dead as a dead do you recollect. i don't have any question -- dead duck but psychotherapy has been life saving. and we both have been fortunate and certainly i speak for myself, to have tremendous psychiatrists who did not make the distinction between psycho farpsychopharmacology and puttig it over here and sigh he co-therapy over here and he did both with ease and grace and tremendous skill learning an enormous amount about the illness and enormous about the human condition and human nature. it's just tremendously important. >> it's so beautiful about this is one tends to think of psychotherapy and drugs as working in very different ways. one has talked therapy and the other is biological. and now it's clear that from

elyn's studies and other people's studies that psychotherapy works on the brain brain. it's a biological treatment. >> charlie: okay. so the sigh scwo psychotherapy a biological change in the brain. >> it's like a biological treatment. when you and i are having a conversation it changes our brain. >> the important thing to keep in mind is when you're talking about mood disorders, bipolar disorders, depression and schizophrenia, we're talking about a pathologic condition that medication helps to restore the neurochemical balance but that in addition, the value of psychotherapy, and i'm going to say something that's a little bit provocative but that it's the therapy but it's also fundamentally the consistent, the supportive and the healthy relationship that the individual giving -- >> absolutely, absolutely. these are the key ingredients to basically turning around mental

illness this and making people be able to achieve what kay and elyn have as opposed to living a life of de dis pair. >> i was expected to live independently. i think if i just had medication that would have happened and if i had therapy that would have happened but together they worked very we. people think psycho dynamic therapy is awful for schizophrenia and i think it really helps some including me. >> certainly in jeff's department, psychotherapy and drugs go together. el instance's case is very different. therefore people with schizophrenia who avail themself of psycho analysis. you discuss it very nicely in your book and many so your talks that it helped you. >> i think first of all stress is bad for all illnesses, in particular mental illness and

psychotherapy helps you to avoid with or cope with stressors. second it helps you develop more psychological mindedness and stronger observing ego so you can take a step back and observe what's going on your mind. third it helps you come to terms with a blow to your self-esteem having a mental illness. it's a place where you can beret your chaotic, scary and destructive thoughts and say it outloud. >> that's beautifully said. >> charlie: and know you're not alone. >> yes. >> the reality is that hour current reimbursement systems, how we pay for mental healthcare does not support your optimal treatment. >> we are fortunate -- >> and it's the standard of care by anybody's study of the studies. i mean that psychotherapy and medication is pert than either one alone. but reimbursement system is such -- >> charlie: wait a minute, reimbursement system, are you talking about insurance companies are not recognizing this. >> medicaid and medicare.

>> charlie: medicare is too. >> it's not, it's not. kay and elyn had the resources and the families and the intelligence to know how to seek the best treatment. but standard payment for healthcare if it's not out of pocket does not pay for these services. >> charlie: what's their rationale. what do they say is a reason. >> cost containment. >> it's cost containment although it's shortsighted in the sense that one of the other major reasons for psychotherapy is effectiveness is it doesn't do you any good to have effective medications if people don't take them. and the major clinical problem in treating bipolar is not that we don't have medication is that people won't take it. >> and schizophrenia -- don't like to be on drugs. >> for a lot of reasons good and bad, psycho therapy helps with that. >> charlie: sig psychotherapy helps keep you on your drugs. >> the physician makes sure you take it. there's another part. this is not an area i'm an

expert in jeff so correct me if i'm wrong. there is a bias towards mental illness that still persists to a certain degree and this is reflected in the reimbursement. i'v>> it's gotten better, it's ku6rd by federal law is really very generous now with mental healthcare and i'm getting quite a bit of my psycho analysis paid for. it's better for many people. >> social policies and really self defeating because healthcare expenditures are a huge concern to the economy. we don't support the services that we know will reduce the morbidity of illness that's cost efficient. , sr. >> i think one of the reasons that is such a historic occasion to see people with serious illnesses who aren't appropriately treated have a fantastic life. they contribute importantly to society. >> they are not the typical face of people you think of for mental illness, you think of the psychotic killer or the deranged individual. not productive individuals who

have success fifth careers. >> charlie: under what circumstances do psychotherapy and medication fail. >> the fact that it's very clear that despite the fact that there are many many medications, that can work in individuals and a number of evidence-based psychotherapy some people don't get better with some combination of anything we've got much the good news is the best treatment for depression we've had for a very long time is lack of convulsive therapy and that can get people out of an episode where they may be suicidal or moribund. on the other hand the more medications you failed the less likely it will keep you well and it has side effects. so we're in a situation that we have people that are suffering in the way we've heard described that there is nothing that we can do and they are, it's a malignant situation. >> you went beyond this. >> we took a different tact. we said look, we're identifying a circuit in the brain that seems to go wrong with people

when they're depressed. we see that we can correct the circuit function with medication. we can correct the circuit function with cognitive therapy. we can eb even see its correctin with bla placebo when people recover. we started to see certain things happened or you wouldn't get well. what we did we were in the right place at the right time. the work by the neurologist and the neurosurgeons on parkinson's disease recognizing when people stop responding to the medications for parkinson's disease, that by knowing the circuits of parkinson's disease they could target in the circuit directly with focused brain stimulation called deep brain stimulation or an electrode it's placed precisely in the brain by a skilled neurosurgeon and that you could literally tune the abnormal circuit exactly where you knew it was dysfunctional. so we had a hypotheses that we knew the circuit for depression and that we would go directly at

the subclosal singular and we want this area to turn down and everything that talks to that brain region to be affected. and we literally implanted in people who basically ever wanted given up on, we target that area, turned the electricity on and saw some incredible things in the operating room. but more importantly, turned down this region, area 25, the subclosal singularrate and had these people recover. >> charlie: that's the clearing of the mind. >> to make this point is recovery from depression takes time. this is very important to take away from this. in the operating room it's like we were watching the depression waking up. it was not that they had an immediate anti-depressant effect but the psychic pain, they felt differently that something about the illness had been fundamentally changed by that

acute stimulation. but it required continuous stimulation over time to actually maintain the effects. because if you turn it off over several weeks with stress, you will go back to the state you were in. but it tested the idea that you could tune the circuit directly with electricity. >> charlie: schitzophrenia, does it have possibilities in skitschizophrenia. >> absolutely. psychology utilizes three modalities of treatment talk, medication and brain stimulation therapy. the most common form of brain stimulation historically was shock therapy which suffered from a bad reputation which is very undeserved because it's highly effective. elyn has pioneered a technique developed for parkinson's disease where you have a single lesion, a specific an tunnellic focus that you can say this is where the pathology is and then attack it with electrodes.

in schizophrenia, we have three different circuits that are dysfunctional. so we have to decide exactly where the electrodes should go and we're not quite there yet. ththe. >> the work we've done and our understanding makes one thinking you don't have loss of synapses and loss of nerve cells. there are situations where people can function very well. with schizophrenia, the disease persists for sometime there's very good evidence with other people with loose synaptic connections or it's critical in schizophrenia is what elyn benefited from. early intervention. it's true for all sack yi yak tk illnesses. the earlier you can diagnose it. the patients like to deceive themselves as both of you. and the families like to deceive thethemselves. so we need to remove the stigma taught. if you had pain your parents would not say let's wait a few days and see what this is about. >> it's just a pain.

>> charlie: what do you think about all this. >> i think what eric just said is important from the jeanette ig genetic contribution. we want the genes restored so they can perhaps be more responsive to therapeutics and prevent the onset. >> charlie: how are we doing on that? >> we're coming along. the idea is to idea a few genes that play a big role and that gives us a toe hold into the by biochemistry of what's going on in the brain. it's like helen said. there's a lot of circuits and pathways where the genes are contributing. the highway with every gene is the stop light or the stop sign. each individual gene can be changed but it has the same effect on how the traffic flows. and that's part of the difficulty in identifying these genes is it's so complex. if you just look at the snaps alone, there are hundreds of

proteins. >> charlie: so in everything we're talking about here in terms of depression and disorder and schizophrenia we're all talking about treatment so far. where is cure? stigma taught. > that's on the horizon. but if treated promptly and effectively can be stopped in their tracks so we're talking about remission within our grasp if we simply get our act in order in terms of cure, cure will depend on the identification of the genes and the ability to preempt the illness prior. >> charlie: prevention. >> there's an important thing charlie to realize and that is many many illnesses are like this. there is no cure for diabetes. it's a life long illness. there's no cure for hypertension. there are dozens of diseases that you can name. in fact most of the common

diseases, it's a question of good therapy and then maintaining that therapy with watchful waiting. and we see two spectacularly rich lives here of people who still suffer from the disease. but it's under very good control. so i think what has to come to grips request the fact that for a long time we will not be able to have cures but that this, one doesn't have the effect of cures, that is people living with the disease, struggling periodically but most of the time being able to lead a rich life. >> i want to make one point also i think with kay and me it's not just that we're successful occupationally but we have rich friends and family. i have a husband who is amazing and a fiance who is amazing. >> one part of this discussion, these are terribly complicated illnesses. that is much much more complicated than hypertension or diabetes. these are probably the most complicated illness in all of medicine. >> charlie: because? >> because it involves the brain and not just the brain the way

it is involved in parkinsons or alateral sclerosis. of the highest most complex function of the brain. >> charlie: what is the question you most want the answer to. >> personally i want the answer to how it is that depression mediated in the brain, what really is the source of the abnormality. we know that gene environment, chemistry, circuits. we're not really getting at the fundamental source of what make negative mood progress into a state of absolute suffering where you can't hold on to anyone else to pump othe pull yf the pit. that's the driving force for me. >> charlie: you've heard me ask this before. >> to go from a gene to behavior and understand all the steps in between is just, would be fantastic. particularly something as complex as a psychiatric disease. >> charlie: how far away are we from that?

>> a long way to get there. >> i think the question i would prioritize is not so much a scientific one as a social one, how can we eliminate stigma. the greatest barrier to making gains both at a research level as well as a treatment level is making society accept mental illnesses, genuine elfnesses that require equal treatment to medical illnesses. >> i've always been interested in the overlap and dysfunctions between normal mood states and cognitive states, intellectual states term an temperment patho. there are interesting similarities and dissimilarities in terms of what's the difference between somebody who is very high voltage enthuse enthusiastic exobject result high energy person and someone who gets on and gets to the

next step over in terms of not manic but enough that it's getting disconturting and out of control. if one of these exist and what is it about human temperment and a wide variety of temperment that a certain number fail or get problematic. i guess trying to keep these conditions within the human condition in some wednesda sensf trying to understand them. >> the easy answer is i would like to find a cause and cure of schizophrenia. that's a long term project and more durable things where studying psychosocial with schizophrenia and bipolar. some are from psycho dynamic. you don't have the equivalent in the drug company funding these studies so it's hard to do them and it's harder to do them for lots of reasons. that's one thing. second, i would like to try to find out ways to use less force with psychiatric patients. i was really traumatized by being in long term restraints,

anywhere from 5 to 20 hours a day for several weeks. they are very painful. >> charlie: how is it. >> four to six points. and the third thing is the stigma point, understanding why and how to combat it. the final thing is not so much something we should know but something we should do is provide the resources so we step up to the plate and give people the abilities to lead full and productive lives. >> charlie: what a remarkable man. what a remarkable story. so looking ahead to even showed 10. -- episode 10. >> in this program we've discussed psychiatric illnesses. in the next program we're going to consider neurological illnesses. there's been spectacular progress in treating certain kinds of neurological illness. parkinson's disease, even stroke, completely new ways of thinking about strokes. moreover we'll have a chance to discuss what is the difference between psychiatric disorders and neurological disorders. these are both brain disorders.

but one of the interesting things is that even though there's some you overlap, one feature about psychiatric disorders is they often reflect extensions of normal behavior. so depression is extension of sadness that you feel disappointed. mania is an, tension of euphoria we feel after a very good program. and ebb schizophrenia, the -- even schizophrenia, the dilutiondelusions some have in t anywheres. one of the things freud emphasize, neurological diseases, fragment behavior often bring out completely surprising features of behavior. for example, there is with certain kinds of strokes, symptom of neglect which a patient will completely ignore an arm or leg that they have because it's paralyzed.

we will sometimes push it out of bed saying this does not belong to me. >> charlie: episode 10, next wunlt. see -- next month, see you then.