Roxana Pop | Staff Photographer
Marina Picciotto, Charles B.G. Murphy Chair in Psychiatry and professor of neurobiology and pharmacology at Yale University School of Medicine, speaks about the science of happiness Thursday morning in the Amphitheater.
When John Lennon wrote “Happiness is a warm gun,” he probably didn’t mean that happiness was created by little neurons firing off in explosions of elation.
If Marina Picciotto had been there, she could have corrected him.
Picciotto, a professor of psychiatry, neurobiology and pharmacology at Yale University, spoke at Thursday’s morning lecture about how the brain creates feelings of happiness. Her lecture differed from those of speakers earlier this week, who spoke about happiness from historical, economic and social points of view.
“We can actually think about happiness in a very reduced way, as a trace from a particular set of neurons in a brain,” Picciotto said.
Picciotto distinguished between “pleasure” and “happiness.” Pleasure is when a person’s circumstances exceed their expectations, she argued. Happiness occurs when a person’s circumstances match expectations.
Dopamine originates in the ventral tegmental area (VTA) of the brain, traveling from one nerve cell to the next and creating an electrical impulse telling the brain’s reward center when something good has happened.
“[The VTA] is important because it’s the site of action for all addictive drugs,” Picciotto said, “but it’s also critical for experiencing the normal pleasures of life.”
In one study, scientists used juice rewards to test primates’ pleasure signals. The scientists observed peaks of high dopamine release when the primates unexpectedly received a drop of grape juice — and chimpanzees really like juice, Picciotto added.
The scientists then made a discovery: After the monkeys had been given juice over and over, a spike of dopamine could be detected in their brains before they had actually received the juice. This dopamine wasn’t a direct result of the juice, but of a trigger causing the expectation of receiving the juice — perhaps the scientist entering the room, for example. They concluded that happiness was a steady stream of satisfaction that followed a rise in dopamine, rather than the spike in dopamine itself, as previously believed.
“Dopamine is not about saying, ‘Reward!’ ” Picciotto said.
And once the studies of behavioral science came along, scientists finally understood why happiness was more than a dopamine spike. For the first time, they began to study how humans assess situations in order to make the best judgment calls.
“Judgments are made because we are matching our behavior to our expectation to probabilities that we can’t fully predict,” Picciotto said. “And that’s what the dopamine signal does. It’s saying, ‘Think about what you’re doing. Make a choice about your behavior.’ ”
This definition of happiness doesn’t mean that expectations have to be lowered, Picciotto said. Instead, one has to be acutely aware of one’s environment and calculate the happiness or satisfaction of an upcoming situation.
“The satisfaction of getting that probability right,” she said, “… I think that’s happiness.”
It is believed that humans will make decisions based on those calculations, she said, thanks to studies that have been done on those with drug addiction.
She warned of manipulating the happiness system.
Taking drugs such as amphetamine, cocaine, nicotine and morphine can all disturb the workings of the dopamine highway, from the VTA to the medial forebrain bundle that carries the dopamine signal. Picciotto said this misuse of the dopamine signal will warp behavior and expectations.
“That will mess up any abilities to predict errors in our environment,” she said.
Drugs cause giant bursts of dopamine in the system that are often time-linked to an event, Picciotto said.
“Whatever was happening when you took that drug is going to be learned as something that will predict a dopamine surge,” she said. “You’ll seek out those cues.”
If someone has a really satisfying cigarette in his or her favorite bar, it increases his or her chances of a return visit to the bar triggering the dopamine release that occurred there the first time.
It makes sense, then, that many American soldiers stationed in Vietnam were heroin addicts during the war, but were able to quit upon their return to the United States — at home, there were no “trigger spots” for them to catch a craving.
The difference in expectation and reality can result in happiness even without drugs, alcohol or addictions involved.
“Our mismatch between the expectation of what could be and what is can be slightly skewed in the way that the mismatch of a drug abuser’s calculation is greatly skewed,” Picciotto said. “What happens when your expectation is based on the judgment of what should be, is that dopamine comes up when you see a picture of Donald Trump’s new boat. The trough comes when you come home and there’s no boat at all.”
If expectations have been raised by personal beliefs, advertisements or the media, the mismatch between those expectations and the reality of the situation can lead to unhappiness. Picciotto said that doesn’t mean a person shouldn’t expect great things, but ought to have realistic expectations.
“But to align our own internal understanding of what is good for us, with the possibilities of the good things that are around us, is something that I think is a recipe for happiness,” Picciotto said.
Q: Please comment on the use of SSRIs and Ritalin in the young and their link to suicide and mass murder.
A: I wouldn’t actually link them to mass murder; I think mass murder is a bigger problem. The increased use of psychoactive drugs by the young is one that, on the one hand, I think I can be extremely beneficial — if any of you have kids that are profoundly depressed, or who are really unable to learn because they can’t pay attention long enough, you know that drugs are useful for certain subsets of kids. I think they’re more widely used for the same reasons that we have talked about here. If the expectation is that we can all work perfectly, that all our brains can work perfectly, then we are dissatisfied if they don’t work perfectly. We are looking for things to actually make us into the ideal person. So yes, our use of drugs is probably much greater than it should be. I worry especially about kids who are prescribed antidepressants and stimulants during critical periods of development, when we know the connections between nerve cells are maturing very rapidly, and they will mature in an environment that has that drugs onboard rather than one that does not. I would also say that it seems likely to me that the overall incidence of depression is also in some ways related to a mismatch in expectation. If we have a school system where, for example, boys are expected to do things they are not able to do — for example, sit still for six hours at a time without recess — it’s a little hard to match that rewarding dopamine signal to the actual realities.
Q: Is there an issue between the dopamine and the prefrontal lobe development of boys that slows that prefrontal lobe?
A: The good thing about neurobiology is that I can always say yes. … The pioneer in this area is the late Patricia Goldman-Rakic — in the frontal lobe, you get a dopamine input that is designed to tune those cells to a perfect match between the inputs from sensory system, from mood systems, from all the systems in the brain to the output of those cells. There’s a real peak, so if you are ill or if your brain does not function well, you might be on this part of the peak. Down in a trough, you’re climbing up the mountain. What dopamine can do, and this has been shown very nicely in schizophrenia, is it can boost you back up to the peak of that curve so that you now have optimal function. What if you are already at the top? What does getting more dopamine do? It just pushes you off the other side of the mountain. So we have evolved these wonderful brains that are designed to react to our environment for optimal tuning. If, for whatever reason, a problem with development, an overactive neurotransmitter system, an imbalance between circuits, if we are not at an optimal level — the psychoactive drugs can actually be very helpful in getting us back up to a tuning place or we can have optimal function. If we’re doing pretty well already, we have the danger of mistuning, and what our brains will do is adapt to that. They will rewire that circuit so that we get back up to the peak. What does that mean when that drug is gone? Once the drug is gone, you won’t be at the peak anymore. All of these factors come into play, not just with drugs, but with everything. It’s an extreme case when you talk about medications, but if I were to have a pleasurable experience like running a marathon, perhaps, or new love, that is going to rewire my brain, too. Just keep that in mind.
Q: Is there a relationship between dopamine and obesity, and is there a difference between people who are prone to obesity and people who are not, in terms of their dopamine?
A: That’s a very timely question. There are many brain systems that are involved with food and appetite. We know that because we actually need food to survive, and in times of scarcity our brains actually evolved …. So a part of our brain simply tells us that we are hungry and we need calories. It matches your need for calories with your food-seeking. That is the hypothalamus. We also have a part of our brain that says, “Learn from that delicious food, go find it again.” That sounds familiar, doesn’t it? That is the dopamine system. So the two are cooperative. The very basic one — that says you need calories, you must eat now. It is very seriously modified by the part that say, “Great deliciousness is good, continue the behaviors that get you to that. ” One of the areas that is very fruitful in research right now is comparing compulsive food-seeking to compulsive drug-seeking. They’re not the same, because you don’t need drugs to survive but you do need food to survive. The way that I think about it is that drugs drive that dopamine system very strongly, and they’re modified by other brain areas. For food, the hypothalamus, that basic calorie-seeking part of the brain drives the behavior and it is modified by this reward pathway. Over time, if the rewarding part of that pathway is stimulated again and again, and if natural rewards, other rewards in your environment aren’t salient or aren’t strong enough, then in fact, you can get to a point where compulsive eating is very similar to compulsive drug seeking.
Q: How do marijuana and alcohol fit into this scenario, and where do you stand on the legalization of marijuana?
A: I stand right here. I think that is a very important question because it is a time when marijuana laws are changing drastically, and I actually had this conversation driving up here. Marijuana and alcohol also feed into the dopamine system, very different pathways, so you can either remove inhibition from the system, which both alcohol and marijuana do, or you can drive the system, which, for example nicotine does, or you can keep the system active for longer, which either cocaine or amphetamine do, so they all do this different ways, but they all come back to this broader, inaccurate dopamine signal. They are all in this same group. Marijuana and alcohol, I would say, are not tremendously different. The concern about either of them is that when you have a legal drug, the exposure to that drug is pretty much universal. I think I could ask if any of you have smoked a cigarette and it would be surprising to me if more than a handful of hands stayed down. Almost everyone has at least tried it. The same is true for alcohol. Why is that? Because it is legal, because the access is there. Is alcohol more harmful or less harmful than marijuana? That can be debated. Neurobiology suggests that both are especially harmful to the developing brain. The curves on how much exposure an individual gets during adolescence or during development and a fairly consistent effects on IQ are quite clear. I think that if marijuana were to be legalized, the key would be to maintain exposure during development as low as possible. The good thing is that we have a success story where we have done that with cigarettes. When I was growing up, something like 50 to 60 percent of mothers smoked during pregnancy because it was OK. We know now that that is really not OK. The number is down to about 13 percent, still pretty high, and we are still very concerned about what the developing brain, what happens to the developing brain with early life nicotine exposure. If the same thing were true, that is, if we came up with a consensus as a society that there are dangers to marijuana and we can actually have a public health campaign, we can limit exposure, that might be a similar case. I think that that argument has to be based on the science, has to be based on what we know about what these various substances do to the brain and what the consequences, especially to adolescents, are.
Q: Is there any new information that will help us treat addicts more successfully, especially young teens?
A: There’s lots of new information and new treatments. I think that the best treatments are combinations of behavior and pharmacological instruments. For example, I have a feeling there some Woody Allen fans in the audience. Do you remember when Alvy Singer was sitting in the classroom, and the kids got up in the classroom and said what they were in their future lives, and the kid got up and said, “I used to be a heroin addict and now I am a methadone addict.” So that argument about pharmacological treatment for drug abuse is one that I think is extremely important, because there’s a difference between a heroin addict who doesn’t have a job and doesn’t have a home and someone who is being treated with methadone and is still dependent on a substance. Just like a diabetic is dependent on insulin, he is able to continue to have a family life, to experience natural rewards again. We do have some pharmacological treatment for smoking, it’s actually gotten pretty good, we have many different ways to treat it. There is the nicotine replacement patch, which does actually work for about one-third of individuals, there is Bupropion, Zyban … All of these things can help make behavioral treatment more effective. We are not so good with cocaine, we are still looking for more effective treatments. There are some newer treatments that are available through clinics that do clinical trials, but I think the key is that for none of these is the drug going to be enough. It is going to be the drug paired with behaviors … That takes a lot of time.
Q: How much can the dopamine expectations be controlled cognitively?
A: One of the things that’s really fantastic about our really big cortex is that they were designed to be superimposed on all of these brain areas that allowed us to survive and to evolve to where we are now. The primary function of those big frontal lobes is to descend and shut things down. I know you want another piece of cupcake. You don’t have to have it now. I know that this is a very difficult situation, but I can now find ways to change my behavior and now get out of this situation. That’s what the prefrontal cortex does. It shuts down the amygdala and the dopamine and says, “Wait your turn.” One of the things that has been extremely effective in terms of targeted behavioral therapy is called cognitive behavioral therapy. What it is doing is training your frontal lobes to be more effective at shutting down those more primitive parts of your brain. There have been some nice imaging studies — they have shown that cognitive behavioral therapy for depression can have very similar effects to antidepressant treatment and sometimes the two together can be even more effective. What it speaks to, I think, is the incredible ability of the brain to be an adaptive organ and to … modify your behavior so that you are more likely to be able to continue to survive.
Q: As someone with ADD, this person says that they have always had trouble delaying satisfaction, in spite of never taking drugs. How does this relate to your studies?
A: It relates really, really well. One of the systems that is clearly different in folks with attentional differences is certainly the dopamine system. The ability to delay gratification also depends on your ability to pay attention and your ability to suppress those lower parts of your brain, screaming for reward. Again, the same kind of treatments, whether it’s cognitive behavioral therapy or pharmacological therapy that help the attention, also tend to help change the calculus and the ability to delay reward. I think that many people with historical difficulty in delaying a reward can teach themselves in situations where there is another, perhaps more or less concrete, reward waiting for them, crean teach themselves overtime to make that calculus in a different way. Some people can’t, and for those people these therapies can ally change that.
Q: Anticipation clearly triggers pleasure. Does remembering pleasure have the same effect?
A: Yes, but I can point you to the neurobiology people doing the work. I can certainly think about things that are pleasurable from my past. I think that the circuits are the same. They likely originate in different parts of the brain, so the memory will originate here in these higher order parts of the brain than the feedback in the end to the same signals. You have to remember that reward, and you have to remember the signal in order to update that calculus overtime. Yes, very cool question, I don’t really have a great answer.
Q: Please define addiction beyond the addiction to substances, such as addiction to gambling on the Internet.
A: That, again, is a very timely topic. Addiction originally was defined based on heroin. We knew what happened when people try to stop taking heroin; they had very intense physiological withdrawal symptoms and those withdrawal symptoms often drove people to go back to the drug. Because of that original conception of addiction, cocaine and nicotine were originally not seen to be that addictive because you didn’t end up having profound autonomic activation, seeing spiders on the wall and all of the things you see in “Trainspotting,” really disgusting. Now we have a broader definition of addiction, which is a compulsion which interferes with normal life, normal pursuit of natural reward. When you have that kind of definition, you can open it up to videogames and tweeting or almost anything else that gives you pleasure and that re-enforces the actions you take in order to get that particular reward. So, can you have a shopping addiction? I think you probably could if you deplete your bank account, making your delayed discounting curve very different. Can you have an Internet addiction? Maybe, if it meant that you really wanted to finish school and you couldn’t. The problem is, that I am not really sure that everyone who has an Internet addiction really wants to be doing something else. That calculus is one that is very individual. I think that overall, if you yourself perceive that particular action, that compulsive action to be something that takes you away from things that you would rather be doing, than you are close to the hallmark of addiction. If it is just that your parents think that it is taking you away from what you should be doing, I am not so sure.
Q: We have learned earlier this week that opportunities like marriage or having a good friend produce enduring happiness. How does that relate to the dopamine?
A: Perfect. … First of all, I want to say that marriage and interactions with other humans, for most of us, definitely make us happy. For a subset of us, not so much. The dopamine signal, to some extent, is more fundamental than some of these other aspects of life that may not apply, for example, to the person who likes to go off into the woods all by him or herself and spend three months without having to talk to anybody. Those human interactions are critical for most of us but are not something fundamental to happiness. But, it is a great example. Imagine that first really fizzy feeling that you feel when you meet the dreamy 17-year-old love of your life. It’s a little bit like compulsive tweeting, I guess. I would guess that everyone here has either told yourself or your siblings or your kids, whoever — careful, it doesn’t last. If you expect it to last and you get married, you may be in trouble; I think we can all map the dopamine curve right on to that. I think a happy marriage is happiness, it’s not fizzy, sometimes it’s yucky, but it gives an incredible satisfaction because it is an expectation of support and reward and connection that hopefully is fulfilled on a regular basis, up and down, but over time, pretty flat. That is happiness. The fizz? That is pleasure.
Q: If happiness involves making good decisions based on our future selves, how do we teach people who make bad decisions to turn around and make good decisions? How is it that the brief burst of euphoria that is related to drug use is able to be of more value than the long-term, really severe punishments?
A: I think that this second question is very important, because in a lot of ways it is the very definition of addiction. Persistent seeking of the substance in the face of punishment, that is the definition of addiction. How is it that that signal is so much more salient? It has changed the part of your brain that actually does that calculus. The long-term negative effects become neglected in the calculation that you make in terms of drug seeking. It is not something that I can explain in terms other than neurobiological terms, because it doesn’t make sense unless we are addicted. Why would you do that? Why would you lose your family, why would you lose your home? Because your dopamine is really messed up. That ability to make good decisions requires a really well-functioning brain that takes the information on an ongoing basis and continues to change your behavior. If you don’t have a system that can make that match, you will not make good decisions. How do you teach someone to make good decisions? Hopefully, they will grow up. For some people, I don’t think you can. Certainly, among all of us we are going to have a varied degree of prefrontal cortical function, the ability to shut down those primitive parts of our brain that are continuing to tell us go do this right now, and for some of us, even therapy or current medications out there are not going to be enough to make us make good decisions. Hopefully, if we are one of those people and we are in bedded in a community of people who can at least help us steer away from the worst decisions, and maybe even save us from some of those bad decisions, we will still survive and still have a life that has some satisfaction, and perhaps even happiness. Overall, maybe one of the best answers to that is that we can’t save everyone from the consequences of their bad decisions. One of the things that is the most salient learning tools is that mismatch. If you make a bad decision but you don’t actually have to change your behavior because of it because you were rescued, maybe, in fact, that is the least likely way to get people to make good decisions.
Q: How is the knowledge about dopamine being used to help with pervasive depressive disorder?
A: One of the ways is through our old-fashioned medication development; knowing that there are other targets and other parts of the brain that could be helped or changed by new drug development is certainly one of the ways. The other way that is helping us to understand both mental illness and addiction and neurological illness is that to some extent it removes some of the stigma from this disorder, so we know are not simply a failure of character. And it’s not enough to say, yes, we know how the brain works and we know how it doesn’t work … that doesn’t make the illness go away. It does, perhaps, start to allow our mental health system and our insurance system to treat those disorders in the same way they do physical disorders. Overtime, I do hope that it will start to open more innovative ways to begin to manipulate the circuits that need to be coherent with the environment and coherent with each other in ways that we can’t think of right now. We develop medications because we know how to do that, we know how to find molecules and then make other molecules change their activity — we have gotten pretty good at it, actually. There have to be things that are out there, and I think a lot about bioengineering and I think about things that are miraculous that we could not have imagined even five years ago. People with congenitive deafness who get a cochlear implant and hear for the first time people talking to them. … The artificial retina allows people with congenital blindness to see for the first time. We can make the blind see, we can make the deaf hear. Don’t you think that bioengineering can also tweak our brains in a way that allow our brains to adapt to our environment in a more logical and consistent way? That’s my hope.
Q: Can you discuss the surge in dopamine and its role in overdosing?
A: It is not the surge in dopamine that actually kills you. The good thing is that most of the drugs that we take are not killing us with pleasure — the surge in dopamine is one that changes brain function but doesn’t stop your heart or breathing. Overdose, for example, of alcohol, occurs because it is a very strong autonomic depressant. Overdose from opiates — it’s the same thing. It is your body that shuts down and not your brain. Do you think that withdrawal can kill you? Like, drug withdrawal? Actually, it cannot, except for one drug: alcohol. So you may want to die if you’re a heroin abuser and you go through withdrawal; but in fact, it is not physically that dangerous. Alcohol, on the other hand, is. What alcohol does is stimulate the parts of your brain that are inhibitory. Your brain adapts. If you are a very heavy alcohol user and you have alcohol on board all of the time, your brain shifts so that there is less GABA [gamma-Aminobutyric acid]. When you stimulate GABA, you become closer to normal. What happens if you all of a sudden go cold turkey and you aren’t stimulating that GABA anymore? The brain has adapted, it has less GABA, and you have seizures and actually do have the risk of death. The adaptation … could kill you.
Q: Are their implications for the treatment of criminal offenders from the findings of your neurobiology?
A: I can unequivocally say that someone who is a repeat drug abuser needs to be treated and not incarcerated. Being addicted does not absolve you from responsibility for your actions. If you were to kill someone because you are an addict, you would still need to pay or in some way incur the consequences of that action; but if we simply have people who are breaking our drug laws because they have this inescapable need to seek that drug over money, over natural rewards, over family, putting them in prison is simply not the answer.
Q: Is there any free will from a neuropsychological perspective?
A: Good humanists know that of course we have free will. Scientists may say that it comes from quantum mechanics, but there is no question at all of the things that I’m talking about, all of the brain states that I’m talking about, give you a propensity towards a particular behavior … We know that even people who are profoundly addicted can quit … we know that people who are profoundly obese can lose weight — Is it easy? Absolutely not. It is almost unimaginable how difficult it is. I think the problem with bringing free will into the equation is is that it is sometimes used as a way to say your inability to change your behavior is a failure of your character. “Look at me, I’m a senator, I quit smoking, obviously its not addictive.” Really? We have to realize that free will is not unconditional. Your free will and my free will are dependent on our environment, our history, our current circumstance, our genetics and our brains. Your free will and my free will are not the same. If we understand that, then yeah, we have free will.
—Transcribed by Mark Haymond