ADHD: Biological Condition or Cultural Creation? Podcast with Stephen Hinshaw

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Transcript

Stephan Hinshaw - 00:00: The invention of ADHD is we make everybody sit still and do very unusual things for five, six, seven, eight year olds to do. Does that mean ADHD is totally cultural? There's no biological reality? No. It does mean that we should really think how we educate. Is it one size fits all? Should there be more action rather than sitting in classrooms? Should we have more physical education? What are the right context to let people with different genetic configurations and behavioral styles thrive?

Intro - 00:00: HumanOS, learn, master, achieve.

Dan Pardi - 00:00: Expertise. What is it? It is a term that is used rather cheaply. Often, self-ascribed by an individual to towards a one's own belief about their subject knowledge. It's often ascribed by somebody who has an interest in a subject or who has spent time thinking about it pretty deeply.

00:00: There's an old saying, when you graduate with your bachelor's degree, you think you know everything. When you graduate with your master's, you realize you know nothing. When you graduate with your Ph.D., you realize that nobody else knows anything either. It's an idea that highlights the expansiveness of knowledge, true knowledge. It implies that the more you learn, the more you realize and grasp the true complexities of the subject and our own limitations of understanding it.

00:00: Years ago, I was grappling with this idea. Is the most knowledgeable person in the world on a subject the only person who can be considered an expert? I think not. Years ago, I formulated a structure, really, just for myself, to capture the different levels of expertise. There are four levels.

00:00: Level one, this is somebody who has taken a very sincere interest in the subject. Whether for personal or professional reasons. They have dedicated a significant amount of time to understand what is known. They have done lots of reading and perhaps they've even created materials, whether writing or solution models to either better understand or to try to solve the situation. This can be personal quest or it could be a public one. Their ideas are out there for many to read and to explore.

00:00: Many of the best people in the health sphere are what I consider level one experts. A level two expert has advanced the field in a more significant way. Usually, by means of a peer reviewed publication. It means that their work has been recognized by a group of expert peers to have an adequate merit to be considered for publication into the sphere or scientific knowledge.

00:00: Level three goes beyond that, and it's usually defined by professorship. It's the life dedication to a subject. It's your career. Multiple publications. Perhaps you even have a group of people that are working under your direction towards advancing the knowledge again on the subject or related subjects.

00:00: Level four is when you are at the top of your field. You have a career marked by advancing knowledge on a subject. Other research is based on your work. Public policy is shaped by your work, and people are living better lives because of your contributions.

00:00: Today's guest is Professor Stephen Hinshaw, and he is a level four expert on the condition of attention deficit. Without further ado, Steve, thank you so much for joining us at humanOS Radio. Let's begin by telling us how you got into your field of study? Where you're working, and what you're doing research on currently?

Stephen Hinshaw - 00:00: It's a long story and I'll try to keep it short. I'm at both UC Berkeley and UC San Francisco now. I'm a clinical and developmental psychologist. I got interested in psychology a long time ago. During college, I decided to change from pre-medicine to psychology, because that was the moment that my father decided to go against medical advice and open up and tell me every time I'd return to the Midwest Home about his lifelong, utterly severe episodes of mental illness, turned out to be bipolar disorder, although it had been misdiagnosed.

00:00: What the doctors had told him when my sister and I were quite young, never to tell his children about mental illness. It would have permanently destroyed us. Our family was in constant silence.

00:00: From my first 18 years, Midwest was a good place to grow up, but I always knew something wasn't being said. Once I learned the truth and then finally helped get dad the right diagnosis, psychology seemed like the way to go. How to learn about kids, and families, and genes, and environments, and the whole mental health enterprise.

00:00: I've ended up after directing schools and summer camps for kids, very clinically applied focus as well as basic research. Trying to study the causes of attention deficits in kids, mood disorders in kids, learning problems in kids, how to work with families, how genes interact with context and producing these conditions. Overtime, as I've matured, taking a broad view of why all of these mental health conditions in kids, teens and adults continue to receive the stigma that they do.

00:00: I'm a multiple levels [inaudible 00:04:58] kind of researcher going inside the body and looking at biological factors in the homes, in the schools, into peer groups, all the way to the cultural large.

Dan Pardi - 00:00: I first met you when you gave a public lecture at the Mill Valley Library to a packed audience and I was so impressed with how masterful you were at just that. From 30,000 foot view all the way down to the molecular level of attention deficit.

00:00: Obviously, there's a lot of different things related to psychological conditions that we could discuss. Perhaps, today we could focus more on ADHD and what has, I think, grown into something that has been recognized, to now something that perhaps is maybe being over-diagnosed. We'll discuss that.

00:00: Maybe you could tell us a little bit about the history of attention deficit. When did it actually get named and what was the early science around that condition?

Stephen Hinshaw - 00:00: About 200 years ago in developed nations, mainly the United Kingdom, clinicians and scientists started to write about, mainly, boys who had problems focusing in what was then new invention of society, compulsory education. Boys were thought to have, what were then called, moral flaws or defects. Not meaning that they were immoral, but that they seem to have good intelligence, but that they couldn't contain their behavior, with today, called as impulsivity.

00:00: Over the decades, the name of this thing changed from, in the early 20th century, minimal brain damage after World War II, the Influenza epidemic that killed 60 million people around the world, left in many survivors with real severe difficulties in paying attention and controlling impulses.

00:00: It was assumed that there must have been from this virus some minimal brain damage that caused the symptoms. There was no brain scanning them. There was no actual evidence. The name got softened a minimal brain dysfunction, then more descriptively, the hyperactivity or hyperkinesis.

00:00: Over the last 30 years, the name has stayed with ADD, attention deficit disorder, or ADHD, attention deficit hyperactivity disorder. Under the assumption that the actual brain areas involved have to do with focus, controlling distractions, managing your impulses. In many cases, not being able to restrain extraneous motor activity.

00:00: ADHD is the current lingo. Some say that it's really an inhibitory deficit disorder, or a motivational deficit disorder. There's lots of theories and lots of increasing brain evidence as to an interesting fact. For some people, focusing attention is a big problem. For others, it's really that inhibitory control. You're at that birthday party. Those candles right on top of the cake and the cake frosting smells so good and you blow out those candles, but it wasn't your birthday party. It was the other kid's. You couldn't restrain that impulse. Of course, this will get kids into how water.

00:00: Another old theory is that it's really about intrinsic motivation. Most people need rewards early to get project started and then they get that sense of satisfaction from doing it them self. What if you didn't have enough receptors for dopamine in key subcortical areas of the brain? You might need those rewards constantly, because that intrinsic motivation never develops.

00:00: To sum up here, we have an instance of what the fancy term would be, equifinality. For some people, there does seem to be an attention deficit. Others, larger problems in executive functions, like working memory and planning. Other people have inhibitory problems. Others it's this sense of developing intrinsic motivation.

00:00: For the most severe cases we see, it's probably all of the above. Multiple roads lead to Rome in developmental psychopathology. There's multiple brain regions in systems that come online. Let's go back to 200 years ago. What brought this into existence in the first place? Compulsory education. How to gather societies, agrarian societies. We didn't make everybody, only the rich kids, kids of royalty who learned to read previously. Now, with everybody having to do it, that's subset of the population. Maybe 5% to 7% who had some inborn problems in developing these regulatory systems were now exposed or revealed.

00:00: It's an interesting proposition I think that ADHD is extremely genetically heritable as we call it. It's also revealed by a cultural shift, illiteracy, so it's both biological and cultural in origins.

Dan Pardi - 00:00: I'm laughing, or I was laughing earlier because I have a three old at a birthday party that face dove into the cake while the kid who's birthday it was was blowing out the candles.

Stephen Hinshaw - 00:00: That's typical three old behavior. Frontal lobes, they take until the mid 20s to mature. If you do that at 8, 9, or 10, and I've seen those face plants into birthday cakes too, even at our sons birthday parties for friends. What do other kids thing, "He's weird." Of course, it could be a girl too, "She's acting weird." They seem like they can get their act together most of the time. What's the matter with them?

00:00: It turns out that you might think stereotypically, "This is a problem of attention. You have difficulties in school, but with a little help, maybe medication, you can do better." It turns out that peers dislike kids with ADHD on average more than they dislike depressed or autistic or delinquent kids, because these are kids who seem to have it together but then wildly impulsively act out sporadically leaving the kids scratching their heads.

00:00: Why is this important? Peer rejection in elementary school is the single biggest predictor 20 years later of school drop out delinquency and needing mental health services by your late 20s, early 30s.

00:00: There's something about not being schooled by your peers, being expelled from peer group school if you will, that leaves you in alert to develop socially.

00:00: ADHD spills out into rampant, often, academic problems, major social problems and very high risk for accidental injury. Many people in societies say, "Well, this is just bothersome behavior. We don't tolerate deviance and fidgetiness. It's not really an issue. Rates of severe injury and death are much higher in five year old of ADHD, 15 year olds, all the way up the scale including driving accidents when people get older.

00:00: It's both the attentional lapses and that poor impulse control that can really cause physical as well as mental and emotional consequences.

Dan Pardi - 00:00: Also, really interesting to hear you talk about how there are, really, different conditions that lead to a similar behavioral phenotype. Whether it's alternations in subcortical dopamine receptors, to alterations in executive functions in working memory. There's different backend causes that can then lead to very similar displays of behaviors. Are they all equally treatable? Does it actually matter as a clinician or as a researcher to try to identify what is actually the root cause, or is the treatment really the same?

Stephen Hinshaw - 00:00: That's a fascinating question. Let's just go outside the box for a second, think of depression. People who suffer recurrent major depressions. This equifinal perspective is just as applicable there. Some people grow up in families where there's been generations of people with severe mood disorders. Other people don't seem to have any family history liability, but have had major loss events repeatedly. Still, others might have been maltreated as kids. All of these are different causal halfways leading to what looks pretty similarly as major depression in adulthood.

00:00: Of course, you'd think with example of depression or back to ADHD, that we need to know the precise causal pathway in order to direct a treatment. You have to know for example if meningitis is bacterial or viral to know whether to give antibiotics or not. We don't know enough the brain yet. There's only perhaps a hundred trillion synapses actively firing the brain at any moment. Almost infinite levels of connections are fascinating. How do they reveal consciousness?

00:00: Maybe right now, the best we can do is find the underlying dimensions of symptoms and find whether it's a biological treatment, like a medication or, to my mind, more importantly family and school based treatments to teach the skills the skills to cope with their attentional problems and learn better executive functions and better behavioral regulation.

00:00: Maybe in 30, 50 more years, when the brain science has really caught up with the behavioral syndromes, we will have very precise treatments for these underlying dimensions. We're not quite there yet.

Dan Pardi - 00:00: That's been a big aha for me over the last, probably, 5 or 10 years, recognizing that the behavioral treatment to any psychological condition, or many, is equal, if not more, important than the pharmacological treatment that accompanies it. For example, with insomnia, CBT, cognitive behavioral therapy. Definitely long term, more effective than taking Ambien. Which, actually, taking Ambien or any sort of sedative hypnotic long term is probably not good at all in fact.

00:00: That doesn't apply universally, but definitely interesting to hear that something like behavioral impulsivity, things like that, inability to sustain attention. There's a behavioral side to that. Are there any sub-conditions of ADHD that are exclusively responsive to the pharmacological intervention, versus having an effective behavioral component to it? Do you have attention deficit in any way? Is there always a behavioral component that is going to augment, if not, be even more beneficial than the pharmacological therapy.

Stephen Hinshaw - 00:00: I think this later statement is more on the right track. I was involved a while ago with a major cross-national study called the MTA, the multi-modal treatment study for ADHD, MTA, where we randomly assigned to almost 600 kids, six center around the United States, all of whom were carefully diagnosed with ADHD, 8 to 10 hour assessment. This wasn't the 10 minute pediatrician's office cursory look that might lead to over-diagnosis.

00:00: With this very carefully diagnosed group, we randomly assigned them to get first, condition one, an intensive behavioral modification treatment. Thirty-five parent training sessions, consultation with teachers, an intensive eight week summer camp and aid in that kid's classroom during year two of the study. Kitchen sink of trying to teach academic and social skills.

00:00: Condition two was very well delivered stimulant medication. We got the right pill. We got the right dose. We had to do trial and error to do that over the first month. Thirty minute visit with a very well trained doctor. Every month, a monitor.

00:00: Condition three was both together, the Cadillac treatment. A lot of families were hoping they'd get that at the beginning of the trial, but it was a one in four chance. Our fourth condition was what we call a community treatment as usual condition. Families could get whatever they could find for themselves with their pediatricians, schools, et cetera.

00:00: What's the bottom line? For these kids with carefully diagnosed ADHD. Quickly and, often, pretty efficiently, within a few weeks, medication, as we gave it in our study, not out of the community, which wasn't done as well, led to symptom reduction. The symptoms reduced within four weeks on average and maintained at a low level for the rest of the year and a half of the trial.

00:00: However, if your goal is not simply to reduce symptoms, but to decrease depression, which often coexist with ADHD or aggressive, even delinquent behavior, and to improve school work, reading and math. To improve the families functioning at home. To have more authoritative home and reasoned parenting, and to help the kids in their peer relationships. It was quite clear that the optimal outcome came from the combination of well-delivered medicine and this intensive behavior therapy.

00:00: It depends on what your goals are. You want to get rid of the symptoms quick in 80% plus of cases, medications work. There are mild side effects. They can usually be adjusted. There's a lot of controversy about whether medications are poisonous for these kids, that the stimulants are oddly very safe if prescribed well.

00:00: If your goal is academic and social competence and treat the whole child, medications may tune the brain better, but you've got to work with the kid, and in the schools, and in the homes to really do this holistic multi-modal competency based intervention.

00:00: Just to take another example again, let's say we were out of psychiatry and psychology for a minute into blood pressure. If you walk in and your blood pressure is 300 over 200, that doctor better get out of prescription pad pretty quick. We don't have time. This is a health crisis, but to start off with diet and exercise.

00:00: If you go in at whatever the standards, and they're constantly set, 145 over 95 in that borderline to high range, maybe the best long term results are going to be from lifestyle change, getting a better exercise regiment. Watching your diet, and medications maybe added as needed to that to tweak and get you into right range.

00:00: Psychiatric illness is a lot like medical illness. Often, the treatments we give, and whether you add a biological component, depends on severity. Medications often don't have lasting effects, especially after you stop the medication. If you can change the environment and change the inner workings of the person's mind, maybe, and it's a maybe, because we don't have great long term data for any psychiatric condition yet. Maybe then you've got a longer term solution.

Dan Pardi - 00:00: Can long term medication therapy actually cure the condition in some people if over that period of time they establish a better behavior set where they don't engage in the negative behaviors that have serious consequences? If, over years, they become a person who does things a certain way, can you withdraw the medication and have those positive behaviors persist?

Stephen Hinshaw - 00:00: This is a great question and a very difficult one. We're going to choose another example again. Let's go to bipolar disorder. It used to be called manic depressive illness. People with this very difficult combination of manias and depressions alternating or sometimes appearing together throughout one's life.

00:00: Bipolar illness has probably the highest heritability or genetic liability of almost any psychiatric condition we know of. Genes, rather than child rearing passes this along.

00:00: For someone with bipolar disorder, untreated, nearly 50% will make serious attempt on their lives, and about 20% overall will complete suicide. This is lethal. The stereotype is, "Oh, you're giddy, you're euphoric. Mania is no big deal." The poor judgement, the psychotic delusions that come into play, the impulse control problems are huge.

00:00: The medical rule thumb today is you're playing with fire. Often, people with bipolar illness may need to be on medications for long periods of time. The medications figulate the firing [inaudible 00:18:55] regions, squelching these episode also allow the person to develop job skills and better relationship skills, and a whole bunch of life skills. There's some who would say that if you've been symptom free for a time, maybe we could taper that medication. That's true for unipolar depression more than bipolar with that high suicide liability.

00:00: What about ADHD? Here, the genetic liability is almost as high as it is for bipolar disorder. Medication help you focus, help you remember, "Oh, you know? It's that other kid's birthday. Not mine." You got that impulse control, that inhibitory control goosed up a bit.

00:00: Maybe then you're better able to learn in school. Maybe then you're better able to learn from peers. Overtime, of course, we haven't randomly assigned 10,000 kids with ADHD the medicine for the next 20 years, 10,000 the placebo. It's unethical we couldn't do it. It would be a hugely expensive study.

00:00: Overtime, medication alone as effective as it can be in the short term doesn't teach those skills. It doesn't prevent, on average, delinquency in school failure. My strong suspicion based on the research I've done and many others have done is the medicine primes a brain, but the real lasting benefits are going to come from lifestyle change, getting the family and teachers, and when you're an adult, employers and spouses on board, and knowing what the triggers are. A lot of people, adults with ADHD do better in self-employed rather than assembly line jobs, because attention is better. Motivation is stronger when you're calling your own shots rather than someone else.

00:00: Long story short, we don't know yet who, which subgroups are going to need medication for a long time. Who might need it for a relatively short time to get the skills goosed up. Of course, it probably depends on severity. The bottom line is, unless a doctor is working closely with the family, monitoring treatment regularly, not once a year with a five minute, "How is he or she doing?" We won't know which way to gear treatments.

Dan Pardi - 00:00: Let's talk about medications. Maybe we could just do a brief review of the types of medications that are used and in whom they are used. The differences. You might select this type of patient with this medication. That will kickoff the conversation for the rest of the interview here. Let's talk about meds.

Stephen Hinshaw - 00:00: The main class of meds used for ADHD are stimulants. You think already, "Wait a minute. Why would you stimulate the brain of somebody who's already sped up?" The theory for a long time was people with ADHD have paradoxical brains. They respond to stimulants by slowing down. There must be something really funny in the wiring there.

00:00: We have to back up. Stimulants are ... If we termed it better, SDRIs, selective dopamine reuptake inhibitors. Most people know what an SSRI is, they've been in the news for 20 plus years, selective serotonin reuptake inhibitors. Serotonin squirts out [inaudible 00:21:48] on the chain, stays in the synaptic cleft, hits the receptor, but pretty quickly gets grabbed back up by that first neuron.

00:00: The SSRI blocks that process of reuptake, at least more serotonin out there for firing. Stimulants or SDRIs, they do the same thing for dopamine, and also for the key neurotransmitter norepinephrine. They're really SDNRIs, just to confuse the alphabets.

00:00: While the stimulants are in their bloodstream, there's more dopamine and norepinephrine available synapse to fire on that X-neuron in the chain. What do we see? Within 20 minutes, they're swallowing the pill. Pill leaves your stomach, crosses the blood-brain barrier, starting to work in the central nervous system. Person is better able to focus, because dopamine is a key neurotransmitter for intrinsic motivation on that sense of reward, and for regions and pathways in the brain linked between the frontal lobes and stratum to help you module behavior, somewhat to executive functions and control your impulses.

00:00: Now, not everybody responds to stimulants. Stimulants goose up your pulse and blood pressure a few ticks. They can make it hard to sleep, so you have to make sure the dose doesn't stay too late in your bloodstream in the evening. Stimulants are very short acting. Each morning you start over again. You never build up to what's called a steady state.

00:00: Some people have side effects that don't go away with that tweaking. Another class of medications are the noradrenergic or norepinephrine drugs, like Atomoxetine, the trade name is Strattera. It's an SNRI. It's specifically blocks the reuptake of norepinephrine, and not dopamine. You don't get that quick attentional boost. Over months and longer, you get better impulse control.

00:00: There's a third class of noradrenergic, norepinephrine like drugs that used to be blood pressure medications that workout on the [perifrian 00:23:36] in the brain and get you just in a calm enough state that some of your symptoms dissipate. There's a few other meds that are tried without nearly the evidence.

00:00: What's really important just to talk clinically for a minute is, number one; the medications are not poisonous for somebody with serious ADHD. They really can work. Two, they only work if you have the right medicine at the right dose. In my extensive experience clinically and in research, we know that. Let's take two 10 year old classic boys with ADHD. Same weight, same level of disruptive behavior, et cetera, et cetera. One of them takes a stimulant like methylphenidate or ritalin at a tiny 5 milligram dose a couple of times a day. Shows a great effect.

00:00: The other takes 10 times that much and barely shows an effect. The genes and metabolism within each kid differ enough, but we don't know how to predict that yet. That's what personalized medicine is going to get us toward. Unless the doctor tries a low medium and high dose systematically for a few weeks or even several months and gets parents and teachers to rate the behavior every week to make sure. You don't know how many families come to our study saying, "Dr. Hinshaw, these medicines don't work."

00:00: In our summer programs, you try those response trial and you try another agent if the first one doesn't work. Of course, again, combine that with behavior therapy. All of a sudden, what seemed like a treatment failure is not at all.

Dan Pardi - 00:00: If somebody is on a high dose, it's not necessarily that they've built up a tolerance overtime. It just could be individual sensitivity because of metabolisms in a receptor sensitivity for that drug. High dose is really a relative term.

Stephen Hinshaw - 00:00: It's a relative term. I want to pick up on what you just said about tolerance. The stimulants, if you don't have ADHD, and you're a college student looking for a study advantage, or you're looking to party all night. Stimulants goose up dopamine. They give a sense of euphoria for people like these.

00:00: If you are abusing stimulants or you don't start off doing it that way, but to get that euphoria or that high, tolerance can develop pretty quickly. You're going to need to, over a few weeks, double, triple, quintuple your dose to get that same high that you sought initially.

00:00: Interestingly, for people with ADHD, probably because of genes that are just being discovered, most people with ADHD when they take these medicines don't get a euphoria at all. In fact, if anything, if you study their faces, they get slightly down. A little more focused. Not as rambunctious.

00:00: There maybe some inborn protection against stimulant abuse for people with ADHD, and the tolerance that can build in an abuser very quickly. For somebody with ADHD, of course, if it's a kid, they're going to grow each year. You might need to gradually increase the dose immense the body weight to get drug through the metabolic pathways.

00:00: There is also is concern over what's sometimes called a slow tolerance would, year one, year two, year three, year four, by having your dopamine system in you brain more enhanced and getting the dopamine not reuptaken into that presynaptic neuron as we talked about. Maybe you start to slightly burn out some dopamine circuits.

00:00: People with depression with SSRIs, not everybody. We can't predict this yet. Some years later, you get to that maximum dose and you got to try something else.

00:00: Also, for ADHD, there are some brain imaging evidence that, at least in a subgroup, year after year of treatment may make that pill less effective, but it's not the same as that quick tolerance a drug abuser would get.

Dan Pardi - 00:00: Interesting. That has always been an interest and a question of mine is the long term implications, safety of use of these medications. Whether you're diagnosed with ADHD or if you're somebody that's using these drugs just to enhance performance, which I'm curious to know if you have a specific statistic about the amount of amphetamines that are used just for study performance. There is some thought that these medications can be damaging to dopaminergic systems.

Stephen Hinshaw - 00:00: For people with ADHD, and these medicines have actually ... They're the oldest psychotropic medications of the 20th century. Dr. Bradley in Rhode Island started using stimulants for kids in his residential treatment center in 1938, predating anti-psychotic and antidepressant medications by 15 to 20 years.

00:00: The safety profile, despite the stereotypes and stigma about taking speed, stimulant medications, is pretty darn good if the regiments followed carefully. Where we get into trouble though is with stimulants as "smart pills", performance enhancers, party pills.

00:00: Between 2009 and 13, emergency department admissions for stimulant overdose increased by 360% in the United States. It's really high. During the first 10 years of this century, roughly from 2002 or 3, till 12 or 13, rates of diagnosis of ADHD went up 42% in kids in the United States. That's like an epidemic. This isn't, as far as we know, a communicable disease.

00:00: Why first were those rates of diagnosis going up so high? Direct to consumer advertisements, pushing by pharma to get these pills prescribed. Obviously, they do benefit some kids. Richard Scheffler, health economist at UC Berkeley, and I, wrote a book two years ago called The ADHD Explosion, probing this very issue. Found that a key reason was that in many states who had suddenly put into effect accountability laws for school testing. Accountability laws don't have anything to do with ADHD though to get test scores up.

00:00: In those states that suddenly enacted those laws. Over the next few years, rates of ADHD diagnosis, especially among kids near the poverty line shot up 50%, 60%.

00:00: If the school district, especially the poor urban district is trying to get test scores up. Maybe you get kids on the borderline diagnosed and treated, or maybe, much more insidiously, a kid gets that special ed ADHD diagnosis and their scores are all of a sudden excluded from the district's mean test score.

00:00: There was a [furious 00:29:34] undertone to this too. All these goes by way of saying ADHD is linked to academic and vocational performance. A lot of people, when these rates of diagnosis are going up, that means more high school kids and college kids with this diagnosis have the pills right in the medicine cabinet.

00:00: Do you let your roommate use it, because they've got a midterm coming up? Can you sell Adderall for 5 or 10 bucks a tab? Et cetera, et cetera. The surveys don't have a consistent number. The current estimates are that somewhere between 8% and 25% of college students in the United States without any ADHD at all have been, or are using stimulants to enhance their performance. This is a high number.

00:00: What's the bottom line? The bottom line is twofold. Number one, if you have ADHD, these medicines not just help your attention focus, but that help your working memory. Help you retain information. They have some real learning benefits.

00:00: If you don't have ADHD, the medicines keep you up late. They get that studying done that you put off all semester. The effects on actual learning are almost [inaudible 00:30:37].

00:00: However, point two is this, if you have ADHD and you're followed carefully by a doctor because of some, this genetic protection we talked about. If you're monitored regularly, pretty darn unlikely you're going to get addicted to those stimulants. Under 1%.

00:00: The most current estimates are that 10% to 15% of unsuspecting college students using stimulants as smart pills will end up in the ER for addiction to stimulants. Addiction to stimulants, I just have two words to say, breaking bad. This is not a pretty picture. It's not as quick when you take them orally in pill form. It's when you inject meth which hits your brain and bloodstream within seconds. It's the same mechanism of action.

00:00) My bottom line is this, if society thinks we're going to solve our achievement test problems and become and more productive economically viable society by having just about everybody takes stimulants. I think we're barking up a wrong tree, and I think there's real health risk from doing that.

Dan Pardi - 00:00: Yeah. How normal is it for a child to sit in a chair all day long and be talked at by an adult? You mentioned this in your presentation at the Mill Valley Library, is that biologically. This is an unusual situation that they were putting young children in. Do you really have attention deficit, or do you have conditional attention deficit? Do you have these unusual conditions?

Stephen Hinshaw - 00:00: Let's go way back in time. Let's go back in evolutionary history. Most humans were foragers. Foragers is the new word for hunter-gatherers. Compulsory education ... You learned on the job by accompanying dad on the hunter, mom foraging for food. We didn't make kids sit in one room school houses or factory like giant schools or do the things we do on our post-industrial era today.

00:00: What would have been good? It's good for any species to have genetic diversity in case conditions change. Probably good for some humans to have been pretty darn careful. Others have been more exploratory and impulsive because you're the one who might have found that prey out there.

00:00: Of course, if you're too impulsive and you've only got two arrow and you shoot your wad too quickly. Uh-oh, no food for the tribe for the week. There's always a balance between, let's say, the [inaudible 00:32:44] systems and the exploratory systems of the brain.

00:00: Something interesting happened about 15,000 years ago. Humans who lived in contemporary China, in Asia, climate started to change, last ice age. Et cetera, etcetera. The Bering Strait was then not a strait, but it was a landmass. As climate started to change, some of those individuals started to head over to what we now call Alaska and then down to British Columbia, California. Some of them all the way down to South American.

00:00: Back 15,000 years ago in China, the allele frequency. There's a gene that controls how much receptor action you have for dopamine. There's an allele of that gene that predicts in a small group of people that you've got not quite the same dopamine receptor coverage, makes you more impulsive.

00:00: The gene allele frequency back in China was about 3%. Who were the people who headed off across the Bering Strait landmass? The explorers. Fascinating genetic analysis to our human remains. If you go to modern day Alaska, modern day British Columbia, California, all the way down to Central and South America, that allele frequency goes to 10%, 15%, 20%, 30%, 35%. The people who migrated were people with exploratory genes. That was adaptive in some ways.

00:00: What happened in, I think, 1860? Massachusetts was the first state in America to have compulsory education. A little bit earlier in England. Now, we make every kid sit in a classroom doing things the human brain never evolved to do learn to read. Reading has only been around for 5,000 years.

00:00: When the environment and the context changes drastically, genes that might have been helpful in an earlier time now product behaviors that might not be so adaptive anymore. That's the invention of ADHD, is we make everybody sit still and do very unusual things for 5, 6, 7, 8 year olds to do so we can cover ADHD.

00:00: Now, does that mean ADHD is totally cultural, there's no biological reality? No. The most severe, in terms of impulsive kids in the hunter-gatherer tribe but have gotten to trouble, they're the ones who get into real trouble in current schools. It does mean that we should really think how we educate. Is it one size fits all? Should there be more action, rather than sitting in classrooms? Should we have more physical education? All of a sudden, now this brings in a whole other cultural dimension, not to just individual brains and dopamine and norepinephrine levels in brains, but what are the right context to let people with different genetic configurations and behavioral styles thrive?

Dan Pardi - 00:00: On my blog I've been writing about how physical activity can augment mental performance, and there's two ways to look at it. A consistent physical activity practice and the effect that that has on neurotrophic factors and then even things like executive functioning. Also, the acute effect of doing physical activity now.

00:00: I call my office a lab. The reason I do that is because I test different ways to optimize my ability to think across the day. One of the articles that I wrote about is disability of moderate intensity physical activity, just around a jog to augment blood flow.

00:00: If you go beyond that, the amount of blood flow that goes in the brain will reduce back to the baseline level. You don't necessarily get a boost in thinking ability from blood flow specifically.

00:00: How also muscle activity alone can be another stimuli to the brain to cause cortical arousal. A really interesting story was told by David [Digris 00:35:58] at Stanford. He's a very prominent sleep researcher. It shows the impact of muscle activity on cortical arousal. Eighty-eight hours of sleep deprivation for this one subject where they were doing the extended sleep deprivation study.

00:00: He seemed to be interacting really well with the sleep researchers and had good positive mood. They had him sit down to take the last cognitive test, the psychomotor vigilance test. As soon as he sat down, he started to accuse the researchers that they filled the room with gas. That they were gassing him.

00:00: They looked at each other like, "Gosh, is he hallucinating?" They were very concerned. What they realized is that when he sat down from a standing up position, that lack of muscular activity was one of the few things that was keeping his brain awake. He started to feel like he was being gassed because he had so much sleep pressure.

00:00: Thinking about it, if you're laying down, you're much more likely to feel sleepy if you're taking muscle relaxants. Just that muscular activity is another factor that could keep your cortex alert and stimulated.

Stephen Hinshaw - 00:00: Right. Just to comment on that. Over the last two to three years now, not huge, but medium size, very carefully controlled clinical trials. For kids with ADHD, show unequivocally that 30 minutes of aerobic exercise a day over the course of some weeks helps parent-teacher ratings, even objective measures, activity level, attention, focus, inhibitory control.

00:00: The effect sizes from this aerobic exercise are not as big as they are from stimulant medications of well-delivered behavior therapy. They might augment what we're talking about as holistic treatments to get the body moving. Therefore, the brain moving. Medicine for the kids with the most ... And adults with the most severe conditions. Everybody needs skills.

00:00: There's a few individuals with ADHD who don't have any comorbid conditions. Have pretty good friends. Et cetera. A little dose of stimulants and, boom, they're fine. The vast majority of the time, you got to make up for the academic deficits. Teach better social skills. Learn how to inhibit. Work on executive functions. A multi-modal treatment including exercise is part of the picture.

Dan Pardi - 00:00: Yeah. Also, recognition of your chronotype. When is your brain naturally alerted? Are you a morning person or an evening person? Some people that have real tendencies, which is about 20% of the population lean one way or the other.

00:00: I think particularly for students that have a late chronotype, I wonder how much ADHD is diagnosed by their internal genetic structure that is predicting when their maximal alertness is. If it's not in the morning, is it in the evening? Then you can't concentrate when you need to. That might be the cause.

Stephen Hinshaw - 00:00: I think that's true. Again, we are not at the point, but we're fast getting there to personalize, not just medicine, but all of psychological and psychosocial care. What's your chronotype? What's your genotype? What kinds of meds are you going to respond to with the minimum side effects? Who's going to respond best and some fascinating research in the adult depression world to try to predict? On average, you get equal results with serious depression from SSRI therapy or cognitive behavioral therapy.

00:00: Of course, some people respond better from one than the other, and now we're starting to get statistics and profiles of the person when they walk into the clinic to predict who is going to do best in either one of those or the combination. This is where the field is going. This is where we need to go.

Dan Pardi - 00:00: So that I understand, there are real risks to untreated ADHD for adults and for children. I remember you talked also about in your lecture the extraordinarily higher rates of divorce in untreated adults with ADHD.

00:00: It's a risk balance equation. Should I take [implications 00:39:26]? For some people, the answer is clearly yes. Even if there is a risk of the drug, there's massive consequences for a non-treatment. For people that are taking a low dose overtime and have good behavioral practices in terms of getting enough sleep and physical activity, et cetera. Do we see long term consequences of consistent, but low dose amphetamine usage?

Stephen Hinshaw - 00:00: Let me take this in two parts. First, you started off with talking about some of the impairments. I haven't even mentioned our research on girls with ADHD. We have the largest sample of girls with this condition in the world that we know of now followed into their mid to late 20s.

00:00: Our girls with ADHD, when they started off in elementary school and came to our summer programs. Those who were quite impulsive, not just inattentive, but impulsive. Ten, fifteen years later are showing extraordinary rates os suicide attempts and extra extraordinary rates of, we call, cutting non-suicidal self-injurious behavior, that boys don't show as much. This isn't a passing condition of a lack of focus and being spacey, the health consequences are serious.

00:00: Now, in terms of treatment and in terms of stimulants that do stimulate your wake centers of the brain and keep you up later. This is the problem in part with using stimulants periodically without an ADHD diagnosis. [inaudible 00:40:38] going to take it at night to pull that all-nighter, which is going to disrupt your sleep for that night and probably long beyond.

00:00: Optimally, for somebody with clear ADHD, you're going to want to dose regularly. Make sure the dose is stated out so you do get that sleep in the evening. If you get that dose right and if you've made those doctor initiated adjustments, most kids with ADHD actually somewhat sleep better on medication because they're not as worried at night about how much they screwed up during the day and might have some long term regulatory effects that we just don't know about. It's this inconsistent keeping stimulants as smart pills, stimulants as party pills.

00:00: We know from personal accounts that a lot of people at a frat party or whatever, who are going to drink quite a bit, take stimulants so they can stay up longer and drink more. This is not what we call a medically indicated use of stimulants. There is going to be a long term psychological accident related and sleep consequences if that's the way you're taking these meds.

Dan Pardi - 00:00: A thread of humanOS is looking at ancestral methodologies to support or direct modern day health objectives. Can we look into our past? Like you mentioned. What was lifestyle like before modernity where things have changed so rapidly? What was light exposure like? What was sleeping patterns and physical activity patterns like? How can we use that to thrive optimally now?

00:00: I've been speaking at that conference for years, the ancestral health symposium. I'm an editor for the journal of Evolution and Health. I think it is such a source for us to find ways to, then, improve our lives.

00:00: One thing that's really interesting, if you look at hunter-gatherer patterns is that they will demonstrate very robust circadian rythmicity. They have seemingly more robust alertness drive during the day, and then they have a deeper plummet in the evening. That probably has to do with the amount of light exposure and the pattern of life exposure that they're experiencing over the course of the day. Since light exposure is the main driver of circadian timing and rhythm. The light intensity is massively reduced as we go from outdoors to indoors and we spend all of our time indoor sitting down at a computer, most people.

00:00: I've thought, is there a possibility for low dose stimulants to artificially create greater circadian rythmicity. Higher alertness drive during the day drops off in the evening. You actually feel like going to sleep earlier than you might because you no longer have medication if you haven't taken it at the right time. Right? You might then maintain a better sleep practice and a deeper sleep. Totally speculative. Just an idea that's crossed my mind.

Stephen Hinshaw - 00:00: You've got a great idea for a new research study. Let's collaborate.

Dan Pardi - 00:00: Let's do it.

Stephen Hinshaw - 00:00: It's intuitively quite appealing. Stimulants are very short acting, they last in your bloodstream four hours, or some of the long acting ones, 8 to 10 and they're out at night. It would be made to order referral within subjects medicine placebo trial to see if we got the right biological measures, if what you're suggesting is accurate.

Dan Pardi - 00:00: It's an honor to speak to somebody who has such profound level of expertise on a subject. I really appreciate you coming on to the show. I look forward to bringing you back on to talk about stigmatization of mental disorders and what we need to know in order to address those effectively as well.

Stephen Hinshaw - 00:00: It's been my pleasure, and thanks for the great questions.

Intro - 00:00: Thanks for listening, and come visit us soon at humanos.me.