 Alcohol and drugs are used by a huge amount of people right. Some people do bungie jumping, some people do fast driving, some people do gambling, but there are some people who develop very early problems. So, it would stand to reason that everybody does not have the same risk like in real life, even if all of you ate kilos and kilos of sugar, all of you would not develop diabetes. Some people who are at risk would go on to develop problems. So, part of the thing that we need to know is who is at risk, so you can put in early interventions. Two is what is the risk, so that even if problems develop, you can put in interventions, you can devise interventions. So, that is the second question that we will try and answer, which in this talk I will focus on why are some people at greater risk and if so do we know who they are and why is what is this risk. So, let us go forward and let me be very clear that I am talking about addiction or dependence. There are two major ideas as far as alcohol, drugs all these things are concerned. One is called dependence, where you develop most important, you develop loss of control, that you are not able to control your use, whether it is of gambling, whether it is of alcohol, tobacco etcetera. So, these are some of the criteria that define dependence. There is another great idea, which is called harmful use. I do not need to be dependent, I do not need to be an addict, but I can have a drink, drive and have an accident. I can have two or three drinks, go home, get so upset that I beat up my wife and kids, I am still causing harm. So, for the large majority problems occur without the benefit of having the disease called addiction. And in cultures like ours, where there are no strong rules about who does what, the harmful use of alcohol and drugs is much more. The disease of addiction is similar throughout all cultures, because it is a brain disease. Today, I will be talking about the susceptibility to this particular brain disease. Now, one of the things that I discussed earlier in the morning, is why are human beings prone to using all sorts of substances. They have been doing so from the beginning of recorded time. People have been brewing stuff, people have been taking things from trees and grinding them and having it all to get high. Human beings are invested in getting high and in a way, it is hardwired into our culture. If we do not get high through substances, we get high through bungie jumping. If we do not get high through bungie jumping, we some of us find high is in singing or some of us find high is in working excessively, but getting high is hardwired into the permanent wiring of our brain. It is related to a particular structure in the brain, which is called the reward circuit. The reward circuit is basically there to give a feeling, a sensation of wow, let us do it again. It is there in all animals and the higher you go in evolution, the reward circuit gets more and more sophisticated. Initially, it started out as something, which was meant to motivate you to continue the species. Initially, the whole purpose of the reward circuit was to make sex interesting, because if you did not, you would not continue the species. Then what happened was, you cannot just make sex interesting without making food interesting, because otherwise you would not eat long enough to live long enough to have sex. Then you have to make shelter interesting, then you have to make going for a job interesting, then you have to make poetry interesting, and so on and so forth. As part of the evolutionary drive, evolution is a very stingy process. It uses the same things over and over again. We have this particular circuit, which we use to give us a reward, to motivate us to do things. Human beings learnt a long time back, that if you use a particular substance, they also work on this reward system, and give you a much bigger high, than a relationship, than food, than I would not say chocolate, because chocolate is also technically a drug, but you get the point I am trying to make. But what also happens is, this slide just shows that in the same way, that there is increased activity in this particular circuit for food and sex, there is similar increased activity for drugs in the same area. Now, why do we have this susceptibility? Like I was explaining, this pathway evolved to provide emotional reinforcement for certain choices, and animal makes about food, sex, social interaction. In the middle somewhere, human beings met these substances, which fed into the same areas, and give them a wow, instead of just a wow. But the problem is, that because one is using a particular substance, which the brain was actually not meant for this, we have devised a way of using it to short circuit our brains. So what happens, when the brain fights back, when you give the brain these substances, the brain adapts. And it adapts with a strength, that you have acute effects, immediate effects of using the drug. But you have downstream chronic adaptations, which occur at the genetic levels and molecular levels, which means that you develop persistent long standing behavioral abnormalities. Just as an example, I have borrowed a slide from Dr. Nora Volkow, in the national institute of drug abuse in the US. What Nora Volkow has been looking at, is for example, I do not know whether you can see this, this is the pet scan of a normal subject. And the blue red areas are the areas, where there is increased activity in the reward circuit, which I was talking about. Now, for a person, who has been using drugs for a long time, here methamphetamine, you find that there is reduced activity. So, there is net reduced motivation for things, etcetera. Now, even after the drug user has stopped using drugs, for 24 months that is 2 years, you find there is still reduced activity. So, the point that I am trying to make, is that the brain adaptations that occur, because of continued drug use are very long lasting. So, it is not just a question of asking a person, who has developed an addiction, to say why do not you just make up your mind and stop. Why do not I send you to rehab center, lock you up for 6 months and then you will get better. However, having said that, the question that we now need to ask, is who is at risk? And that is what we will be focusing on today. One thing that we know, is that addiction is a developmental disease. I go further, addiction is a pediatric disease, a disease which happens in children and adolescents. It starts there. So, the younger you start, the greater the risk. If you start as an adult or as an older adult, the risk comes down. So, between 16 to 21, if you start at 16, you have an 80 percent chance of develop an addiction. If you say start at 22, 23, that risk comes down to almost 10 percent, which is why in almost all human societies, you have this, official age at legal drinking, which is pegged between 16 to 21. And in India, mostly it is 21 and why does this happen? This is data that we did from a study in the Andaman islands. This is the entire population of the Andaman islands. And what we found is that, people who started at the age of around, say, between 10 to 15 years of age, as adults, had the greatest, the largest amount of, you know, drank the largest quantities and had the greatest frequency. We had an index quantity into frequency. And for people who started young, they were at greatest risk of developing problems in adult age. People who started later had lower and lower and lower risk. Now, why is this happening? We have established that, it is a developmental disease. Typically, it starts in childhood or adolescence. Also, what we find and these are figures from my treatment center, which is one of the largest treatment centers in India. You find that, 80 percent, almost 80 percent of people who come in for treatment started young or early onset. And late onset constitute a very small number. Again, this is data from my treatment center, where you find that, most of the people who have come for treatment with alcohol and drug related problems started before the age of 20. The second thing that we know is that, not only does it, there is increased risk in people who start young. There is increased risk, where when people have a family history, that addiction seems to run in families. And again, this is our data from India, where we show that people who come from families, where there is early onset substance use, are at much higher risk than people who come from families, which have late onset substance use. The third thing that we know is, addiction is more in persons with externalizing behaviors. For all of you people from psychology, you know what externalizing behaviors mean. Externalizing behaviors is spectrum of behaviors, which include things like, inattention, impulsivity, emotional behavior, that you oppose everything that your parents say, and difficulty in learning from your mistakes. And basically, if you recall what you learnt of child psychology, it has got to do with these disorders like, attention deficit hyperactivity disorder, oppositional behaviors, etcetera. What we do know is that, children who have this kind of difficulties are at much higher risk of developing drug and alcohol problems, as well as risk for other high risk behaviors like, high risk early sexual behaviors, violence, anti social behaviors, etcetera. This is more of the same, these are family studies that we did, which showed that, people who had alcoholism, had a greater family history of the externalizing disorders. The fourth thing that we know is, addiction is strongly associated with certain psychiatric emotional behavioral disorders, especially the mood disorders, depression, etcetera. What we know is that, like I told you, addiction is a brain illness, but it is also more in persons living in stress. People who grow up, whether it is what we call toxic stress, that they cannot escape from the stress, you know. People who grow up with poverty, you cannot escape from poverty, very difficult to malnutrition in childhood, violence in childhood, whether it is family violence, or violence because of war, famine, etcetera. People who grow up, whether it is inconsistent parenting, these are children who are at much higher risk, the question is why. So, basically, if you look at it, these are some of the things, which increase the susceptibility to alcohol dependence. I work with alcohol dependence, because I work in the southern part of the country, where we have more problems with alcohol related problems than opioid drugs like heroin, etcetera. In the northern part of the country, there is a lot more of the other drugs, but alcohol still is the drug of choice throughout India. So, basically early onset, family history, externalizing temperament, psychiatric illness, toxic stress, and of course, culture and availability, these also determine vulnerability. I mean, if I am living in Saudi Arabia, where there is no alcohol to be available, I am hardly going to develop problems with alcohol. I will still develop problems with dune, buggy, racing or some other problems, but not alcohol. So, what we have been doing for the last 20 years is looking at young people. Why do we look at young people? Because older people would have started using the substance anyway. So, once you start using alcohol or tobacco, then your brains change. So, there is no point studying, you do not know which is the chicken, which is the egg. You do not know whether any difference that you find is pre-existing or has started before, after using the substance. So, for the last 20 years, we have been looking at children who have not had their first drop of alcohol, who more or less have not started smoking regularly, but who come from families where there is a very high loading for addiction. And we have been scanning their brains, we have been looking at brain function, especially cognitive functioning and trying to see whether their brain function, their brain brains are different from children who are not at risk. That is, they do not come from the risk factors that I showed you. So, basically this is my high risk and my low risk. And what I am going to talk to you now is what over the last 20 years, we have found. I am going to function mostly on data from my lab, because we are one of the few labs in the world, who work in the vulnerability to addiction. There are three or four more labs throughout the world, who work in this, but we are one of the labs, which have been consistently working in this. So, I am going to focus only on Indian data, because the rest of the data is on the internet, if you are interested. And I would be glad to speak about it, if you are interested. So, what are the differences between the high risk and the low risk? You understood what I mean by high risk and what I mean by low risk, which may influence risk. So, we looked at brain structure, we looked at brain function, we looked at behaviors and we looked at responses to substances. How do these young people respond to these substances? And one of the first things that we found is that there were differences in the gray matter. If you are aware of the brain, the brain has two, on the outside, it is a layer of a gray tissue, which is where all the cells are. And then below you find the white matter, which is where all the tracks are. Basically, if you think of the stations, they are gray. And if you think of the train lines, which connect the stations, they are white, those are the tracks. So, the first thing that we found was that when we looked at these children at risk, their brains were smaller than the brains of children who were not at high risk. Consistently, across 20 years, all the studies we have done. Consistently, across continents, when my colleagues in the US, my colleagues in Germany have been finding this, we have been consistently finding this. And in certain areas of the brain only, not the whole brain. So, what does that mean? These are the, again, if you see the yellow, orange areas are the areas. Basically, what we do is we take brain scans, MRI scans of one group of people, the low risk. And we take brain scans of the high risk and we subtract. And when we subtract, the computerized subtraction gives us areas, where there are differences. So, the yellow areas and the orange areas are areas, where there are differences between the low risk and the high risk. The low risk have smaller brain areas, where these are important. Because, one of the areas where we found smaller was what is called the amygdala. The names are not important. I will just tell you the functions. The amygdala, if you think of the human brain as a car, the amygdala is the engine, because it motivates you to do things. It says, wow, this is lovely, because it gives emotional significance to things and makes you do things. So, it is like the engine. We found that it was smaller, but it was more active. Then, I mean it is that part of the brain, I call it the Nike brain. You see the Nike ad, just do it. That is the brain, which makes you just do it. Alligators have it, crocodiles have it, snakes have it, tortoises have it, lions have it and they just go for it. The snake is not bothered, whether somebody else is watching it, go and grab or act, just goes and takes it. But, you and I are bothered. Why? Because, there is another part of the brain, which are the brakes of the brain, which is the frontal part of the brain, whose job it is to say, wait, think, then do. This is something that the higher animals, the more evolved animals have, because they have to live in societies. So, I cannot just take it from her. I will get slapped. So, what my brain has to do, if you look at the brain functioning, I want it. So, my brain, my Nike brain says, go do it, just take it, just do it. My brakes say, hang on, wait a minute. Let us find out whether you will get into trouble or it will work for you. So, the frontal part of my brain says, hello, can we go to the database and find out, what happened the last time you took a key chain from a young lady. And, there is another part of my brain, which I shall talk about, which is like the gears of the brain, which is the error detector of the brain, whose job it is to see, to learn from mistakes, to learn, should I go this way, should I go that way, should I go up a slope on first gear or should I go on fourth gear. So, that decides, boss, last time you did it, you got thumped. So, this time please do it differently, ask her and take it. So, that is how the brain works. Basically, in a nutshell, the brain is an engine with a car, sorry, brain is a car with a very powerful engine, it has got brakes and gears. But, what we are finding is that the brakes are smaller in these children, who are at high risk. Not only are the brakes smaller, the gears, remember I told you about the error detector of the brain is called the anterior singulate gyrus, but it is the name is not important, but the fact that we have an error detector in the brain. And that we found consistently smaller, which means that in these kids, they are just saying, let us do it. But, there are no brakes saying, hang on, wait, think and do. There is no error detector saying, look, last time you did it, you got into trouble. Do not put your finger into fire again. Do you know kids like this? Do you know people like this? There are people like this. We have been in school with them, sometimes we have been them and these are often people, who are very bright and brilliant people. Because, they just think out of the box, they will come to a solution in two and half seconds and then feel totally bored, because they have cracked the problem before you have even thought of it. But, they get into trouble, because they have a difficulty in sustaining interest. They start off something today and half way through they lose interest and then they go on to something else. So, although they are bright and brilliant, you know most of the tasks that we have in society today, they cannot complete. They are the world's champion starters, they are the world's champion and lousiest initials. So, and we found certain other areas, which was smaller. I am really not going to go into detail about that, as long as I have been able to convey. So, this is basically some of these parts that I was talking about, which are smaller in high-risk children. What? Then we looked at not just the stations, we looked at the tracks, you know, because if the stations are, you know, not good, let us look at the train tracks, you know. Hopefully, the train tracks are good. So, at least the trains will go, the messages will go faster. What we found was very surprising. What we have been consistently again finding is, for example, this is the corpus callosum, which is the white matter track, which links one part of one side of the brain to the other side, the right to the left as the huge fiber. It is the highway, it is a major highway and we found it is smaller and it is smaller at a time, especially in adolescence. We did another procedure, which is called a diffusion tensor imaging. Basically, what it does is, it tracks how water molecules move along these paths. You know, just imagine, water molecules are, you know, trains or cars going along this highway. And if there is a lot of resistance, then the water molecules will not move. Your cars will be stuck, they will be a traffic jam, which in brain sense is good, because it means that there is actually matter there. It is mature. What we found was, water molecules are diffusing every which way, which meant, like you have seen those leaky hose pipes. It was leaking all over the place, which meant that these roads were not well formed. So, not only with the grey matter, the stations not well formed, we found that the white matter, the great highways linking these cities or these stations were also not very well formed. These are some of the pictures. For example, these are the white matter tracks and we found that these orange areas are places where there was leakiness happening. There is too much diffusion happening of the water molecules. So, what we also looked at was that these differences between the high risk and the low risk was maximum when the children were young. And as they grew older, the differences decreased. So, that made us think that this was because of a developmental lag. There was a lag in development. There was a delay in development that these kids were also, their brains were also growing, but 5 steps behind. In fact, some of our colleagues in Canada found that they are almost 5 years behind the other kids in development, in brain age 3 to 5 years. This is also what we found that initially at the age of 8, this is the difference as it goes around the age of 20-22. And in some other studies that we did as late as 3035, the difference narrowed down. This is what these friends of ours have found that on average, these people's brains mature 3 years later than they appears. So, what did we find? We found that in these high risk children, smaller or slow growing grey and white matter during childhood and adolescence. So, how does it affect brain function? We asked ourselves that. Am I with you? Do you need me to repeat anything? Sure, you got the story so far. So, if brain structure is smaller, the question that you need to ask is the brain, is there something wrong with the brain activity? Isn't it? That is the logical choice, the next logical question. So, we asked ourselves as to what happens in brain activity. And to make a long story short, we looked at a particular chemical, which is basically if you like you have an OS operating system in computers. This chemical is the operating system of the brain basically. I won't go into details, but it is very important for brain functioning. And when we looked at it again, we found that they were overlapping curves. The high risk children developed less, I mean slower than the lower risk children. So, the activity was obviously reduced. I am not going to go into this because very technical The other thing that we did was again, this is a technical issue. So, I will try and simplify it. By using magnetic stimulation in the brain, we are able to create electrical fields here so that you can stop or start particular parts of the brain. So, you can see what happens. That is very safe. So, it is not like neurosurgery or anything. So, what we found net net is that when we tried to stop brain functioning by using this magnetic field, you know you can silence brain activity. We found that in the high risk, this is the smaller brain kids, you are not able to silence their brain functioning. The brain is so hyper active, you could not silence them. Whereas, in the other kids, the lower risk kids, when you give this magnetic stimulation, you are able to stop their brain function. So, what we learnt was that these kids who are at high risk appear to have hyper active, extra active brain activity. Now, that is fascinating because when you look at their outward behavior, you find that they are hyper active, that they cannot stop themselves, that they cannot sustain interest in things. Now, so basically what we did find was that there was alteration in the trajectory of brain development, how the brain grew. This caused changes in the neurochemical function of the brain. This altered the electrical activity of the brain. Now, how did this affect behavior and all you cognitive behaviors might be interested. We found that the smaller volumes very strongly predicted these externalizing behaviors. So, these smaller volumes increased hyper excitable brains were a cause of these externalizing. Behavior, the ADHD, this affected decision making. For example, we gave them a gambling task. These kids were asked to do a quiz and if you answered it correctly, you got a certain amount of money. Sometimes, they were told that this is a risky thing, do not answer it. They would still go and answer it. They would take risky decisions even when they were told and even when they were not told, they would take risky decisions. Another colleague of ours worked on a similar thing and she studied the brain function. You know, you have heard of functional magnetic resonance imaging, which looks at basically brain activity, oxygen utilization in the brain during any particular activity. She found something fascinating. When you give these kids a task, which gives them a reward, the part of the brain, which is the, I showed you the amygdala and all that, which is the Nike brain, that gets very excited. So, that part gets very activated, but when she stopped giving them the reward, this is normal children. When she stopped giving them the reward, the activity shifted to the frontal part of the brain, the brakes, because the brain was saying, forget it, they have been taken for a ride. Let us not get too excited, but with these kids, the high risk kids, whether you give them a reward or you did not give them a reward, that Nike brain kept saying, wow, next time it is going to happen, it is going to happen again, again it is going to happen, which is something that we find in people with addiction or with gambling, that I went there, I got hurt, I am not getting a high any longer, I have got thrown out of school, etcetera, but I will still go, I might get a high this time. I have lost 10 lakhs, but I will still gamble, I might win this time. So, the question then became for us, not why do these people not learn from their mistakes, but it became that, hey, these guys are not capable of learning from their mistakes. So, we need to bring in interventions, which will help them learn from their mistakes. So, we cannot stand in judgment any longer and say, why cannot a person with without 2 legs run the Olympics 100 meters, we need to give them something, so that they can run the Olympics, you understand. So, that is where this research has helped us. This research has helped us move from a moral standpoint saying, hey, there is something wrong with them, to saying, yeah, there is something different and can we help them become you know, very, very effective human beings. So, this is what I was talking about the decision making, this is that thing I was talking about, now let us go back. See, for example, in the this, I was telling you in the controls, this is the part which is responding to the reward. This is the Nike part and then it moves to the frontal part, once the reward stop happening, whereas in the high risk, it remains in the Nike brain. Now, let us go to our study this, what we also find is that these children have reduced social intelligence, you are talking about that, is not it, about how people respond. When we gave these kids emotional faces, we put them in a scanner and we showed them emotional faces, sad, angry, neutral and we saw how they reacted. What we found consistently again was that they were not able to gauge another person's emotion and so, in real life what they would be doing is saying, oh, this girl is angry with me, because she is sitting there doing that. So, I will read a neutral responses and angry responses are threatening response. So, I will then go and say, why are you doing this to me and that is again something that we know about people with this kind of behavior. For example, this is again another test that is used, you know, is this guy worried or is he friendly, what do you think, is this person fantasizing or alarmed. Anyway, that is not the point, the point is that most of you will be able to make this judgment, people with autism cannot make this judgment as used as a test for autistic children. We are also using it with these kids and we find that they are also not able to make this judgment and they do not make this judgment, because the parts of the brain which are used to make these judgments do not function very well. Let us go, this is the test that we were talking about. So, we fear anger, consistently the kids could not distinguish between, they would, you know, think non threat, emotional things as threatening responses and these appeared in areas of the brain which are responsible for modulation of emotion and you find that they are responding much more when they do not need to respond. Now, let me go past, you are talking of cognitive deficits, what we are again consistently finding is that in these children, the high-risk children in red, they have worse functioning on tests of cognitive functioning, especially executive functioning, you know, decision making, problem solving, etcetera. So, basically the point that I am trying to make to you is that alterations in trajectory of the brain occur, I mean, cause neurochemical function deficits, cause altered electrical activity in the brain which then causes certain problems in behavior. We find novelty seeking, these are people who love sensation, new sensations every minute. So, they are seeking novelty all the time, they have poor attention allocation, inability to sustain interest which means that despite their superior intelligence, they are unable to reach their goals, perseveration, inability to change responses to non reward. When the reward is stopped, they still keep behaving as if a reward is going to come, poor decision making, especially appreciation of immediate reward, inability to recognize emotional salience, what is emotionally important. So, they have poor empathy and they have an exaggerated response to stress. And remember, these are not people who are taking any drugs or drinking or doing anything, but those who are at high risk. So, of course, one of the questions that we have is what is causing this developmental lag and I am not going to go into detail, but just to say that we are looking at certain genes and how certain genes are modulated by the environment. Obviously, the environment is interacting with the genes to cause this. One last slide, so what? I mean the question that you should be asking me, so what if you have discovered these in these kids, does not make any difference. Why should they be drinking more and getting into difficulty? Why should they be taking drugs? So, one experiment that we did was not in these children, but in slightly older people who are high risk, we gave them a drink of alcohol. These are people who are already drinking, so we were not introducing them to alcohol. And what we found was fascinating. This is the normal EEG, you have heard of electro and the brain wave, this is the normal brain wave in the low risk people and in the high risk people similarly normal brain wave. When we started, there was nothing to tell the difference between these two. Then we gave them a drink of alcohol. In the low risk people, the normal brain activity continued for some time and then it slipped into what we call the alpha, which is a resting activity, which comes when you close your eyes, which comes when you are relaxing, when you are doing yoga, when you are listening to music, things like that. And it lasted for about 10 minutes and then slipped back into the normal beta rhythm. These people, the high risk young people, we gave them alcohol immediately switched into alpha rhythm, the relaxed rhythm, the Bindas rhythm and it continued for a long period and then went back to the normal rhythm. So, which groups brains were being affected more by the alcohol? The high risk, is it not? Who would have the second drink? There is no prizes for guessing that. Excellent, but then what we did was, we asked them, how drunk do you feel? And what we found was, the high risk, whose brains are getting totally relaxed, said drunk, what drunk? Nothing, anything happen? Nothing, you give us a drink, give us some more, because they were not feeling the negative effects of drunk, getting intoxicated, slurring, inability to walk, all that. Whereas, the low risk people, and their brains were not getting affected, they were not getting a high, but they were getting more of the negative effects of intoxication. So, it is a double thupper, one is your brains are getting very strongly stimulated or relaxed and you do not feel any of the negative effects. And the other group, you are not getting any effect, you are only getting negative effects. So, obviously, who is going to have the second drink and the third and the fourth and the fifth and the 256th, this group? So, that was a fascinating revelation. This is first talked off by a friend of mine called, Mark Shakit, who in the 80s discovered what he called, subjective response to ethanol. I did not know it, in the 80s, I was in college and looking up to all the guys, who could take drink a hell of a lot and not get and then still walk. We used to call them iron stomach, people had iron stomach, but the iron stomach guys developed early problems, you know, all of us who would, you know, sat down after the second drink is still alive. How long we do not know, but still there. So, what I am trying to say to you is that, so what I have presented to you seems to be a logical series of data to explain why some people are at higher risk. And what we have been trying to do, it is no point having this kind of data, unless we can go back to the pediatricians and say, you know what, these kids need a different kind of intervention. You need to go back to the teachers and say, look, these kids need a different kind of intervention, because what happens is, children who are, who have these externalizing syndrome are usually kept at the back of the class, because they are difficult children. They are the brightest children, who are asking the cleverest questions, but asking clever questions is not a good idea in most of our schools. They are the brightest children, who finish their work in two and a half minutes and then they are poking somebody, throwing things at other people and so you get sent to the back of the class. This is the best way of ensuring that you create a problem 20 years down the line. However, I want to bring to your notice that these are the same problems that, you know, I think Christopher Columbus had, he was creating problems in Seville getting drunk and getting into fights. Somebody gave him a boat set go and he went and found what he thought was India, but turned out to be a different continent. This is the same problem that Steve Jobs had and he is written in his autobiography. He was getting absolutely drunk and disorderly and getting high on cannabis in India until somebody showed him something called a computer. He changed the world. This is the same problem that I am not going to name any Indian names. These are people who have talked about it. That is why I am naming it. Michael Phelps, that guy who won so many gold medals. Every time he comes out of the pool, his mother had to keep him away from trouble because the cops were arresting him for drinking and smoking too much. Put him in the pool, give him a project. He changes the world. So, the point I am making to you guys is that this lot is like a sword, double edged sword. It can cut both ways and depending on social circumstances, they can become heroes or they can become zeros. So, I want to end with this last slide that this is the brain of a healthy control given 15 year old given an arithmetic problem and these are the areas of the brain which are using oxygen to solve their problem. This is a 15 year old person with addiction. These are the areas which is using. So, the point is earlier you start the greater the problems because the brain is not mature enough and the more prolonged and more long lasting it is. So, basically this is what I believe is the pathway for addiction and this in a way is also the data which tells you why the earlier you start greater problems you develop, why some people are at higher risk. In fact, I want to leave you with a very revolutionary notion which I am trying to push throughout India and the world which is to say there is no such thing as addiction. It is just an epiphenomenon. It is just a result of an externalizing syndrome. We do not recognize it. So, these young people go and try and find their own solution by drinking, taking drugs etcetera because it normalizes their brain initially. But alcohol and drugs are bad medicines for this condition and they develop problems because you and I do not recognize the condition and we do not help them. And if you help them perhaps you know tomorrow's history will be different. I will end there. Thank you.