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The Queen’s Gambit is Netflix’s critically acclaimed series about a chess prodigy who gets “a little help from her friends.” In this episode we find out what they got right, and wrong, about psychiatric meds and cognitive enhancement.

Published On: 1/11/2020

Duration: 29 minutes

Transcript:

Dr. Aiken: Cognitive problems are one of the most common complaints in my practice – whether the patient has a mood or anxiety disorder, schizophrenia, or ADHD…. It’s problems with memory and concentration that bother them the most:

• “I forget what I went in the room for.” 
• “I repeat things in conversation… it’s embarrassing!” 
• “I’m overwhelmed and don’t know where to start.”

These are the symptoms that cause patients to be unable to work, and they often persist long after the episodes of psychosis, depression, or mania have gone away. 

Kellie Newsome: Patients often want to know if medications can help this, or ask directly for a stimulant prescription. 

Dr. Aiken: I would proceed with caution there, but there is some hope. Most of that research has been done in schizophrenia where these cognitive problems have a name: Negative symptoms of schizophrenia. About two dozen medications have been tried, and about half them have had some success… Christopher Correll and colleagues reviewed them for JAMA Psych in 2017 and concluded that “the effect sizes were inversely correlated with meta-analyzed study quality,” which means the worse the design the better the medication looked. The antidepressants did seem to help negative symptoms in schizophrenia, particularly duloxetine (Cymbalta), but it was a small effect.

Kellie Newsome: That’s interesting because we see a similar trend with those antidepressants in depression. When Michael Posternak wrote in our February 2019 issue that duloxetine had the second best evidence for cognition in depression, right after vortioxetine (Trintellix). And vortioxetine just had a controlled trial for negative symptoms of schizophrenia that Michael reviewed in our October 2020 issue. But what about dementia medications. A lot of my patients with bipolar disorder ask about those. 

Dr. Aiken: There was some excitement in the bipolar field in the early 2000’s, and that culminated in two small controlled trials of galantamine and donepezil that looked at whether they could improve cognitive symptoms of bipolar in euthymic patients. Neither worked very well, which is probably why the findings were not followed up. Donepezil did nothing in the on-off experiment where patients served as their own control, and galantamine did some good and did some harm – it improved memory, but reduced processing speed.

Kellie Newsome:  That’s in line with what I generally see in practice when I try to treat cognitive symptoms of bipolar disorder with medications. I’ve seen people feel tired and slowed down on modafinil, have word finding problems on lamotrigine, and trouble concentrating on lurasidone – but all of these also have evidence to help cognition. So I wonderful if they are really helping some aspects of cognition while harming others, of if the results simply vary a lot by patient.

Dr. Aiken: It’s probably both. We’ve fine-tuned our diagnoses over the years in part on how they respond to medications. That was how the mood disorders – which used to be lumped in one category of “manic depression” got split in two in 1980 – those that responded better to mood stabilizers were called bipolar and those that responded better to antidepressants were called unipolar. But we don’t have anything like that kind of diagnostic precision with cognitive symptoms, so things can get pretty unpredictable when we start to use so-called cognitive enhancing medications in psychiatric patients. What’s right for one may be wrong for another. And chess is a great example of this.

The Queen’s Gambit

Kellie Newsome: OK Dr. Aiken so I know you’ve been wanting to talk about this. The Queen’s Gambit is the most-watched scripted series on Netflix, and I see you have your green and yellow “Chess Team 1986” shirt on. So what can chess teach us about psychiatry?

Dr. Aiken: Gary Kasparov was the first chess champion to lose to a computer in 1997. He called chess the drosophila of reasoning.

Kellie Newsome: Drosophila. drow·saa·fuh·luh. Isn’t that the fruit fly that’s always buzzing around at the bottom of a wine glass?

Dr. Aiken: Yes, and for over a hundred years drosophila has served as the test vehicle for genetic research, mainly because this little insect reproduces so quickly. So Kasparaov’s idea is that chess is the perfect testing grounds for human reasoning. Alfred Binet, who developed the IQ test, had the same notion. And the thought occurred to me as well about 10 years ago when I gave a patient with bipolar II disorder galantamine to help his cognition – it’s not something I would recommend today but back then it was all we had. He came back and said he didn’t notice too much except that his chess game was a lot better.

“The Little Green Pills”: Barbiturates and Chess

Kellie Newsome: Before we get into this more I just want to clear the air about something. A central plot line in The Queen’s Gambit – and this is not much of a spoiler alert because it comes out in the first episode – is that the young chess master uses barbiturates to improve her chess game. They help her visualize the moves. This sounds a bit farfetched to me. I mean, barbiturates are sedatives like benzodiazepines – can they really improve someone’s chess game?

Dr. Aiken: I don’t think so. The Queen’s Gambit had a chess consultant on their staff – it was actually Gary Kasparov – so they got a lot of those details right, but I don’t think they had a psychiatry consultant. Sedatives like benzodiazepines and barbiturates would actually impair the three areas of cognition that chess players need most:

1. Processing speed.  Players have to think through dozens of possible moves at each turn. This is why chess is so mentally exhausting.
2. Spatial memory. What makes the difference between a chess master their visual memory for key combinations on the board. Imagine a board with a knight, a bishop, and a pawn on it, and of course two kings. I’m a novice, so I’d have to think through all the possible moves that each piece could make before figuring out what to do. But a chess master would instantly recognize the relative positions of the pieces and know what to do. They do this by chunking – or breaking down – the chess scene into different components, and those components match up with their visual library of key positions.

And the third is….

1. Reasoning or decision making. To make a decision, the frontal lobes come up with a list of options; then the amygdala assigns emotional weight to each of them and sends them back up to the frontal lobes where it plans the chosen action and executes it. Now in order to assign that emotional weight, we need to remember things that didn’t turn out so well in the past.

Here’s how that looks in real life. Like a lot of people, I’ve been playing more chess since this Netflix series came out, and at first I kept bringing my knight out as my first move when I played black. It felt like a good move – real safe and reasonable. But inevitably my opponent – that is, my son – would move his pawn to attack this reasonable knight and in doing so would soon paralyze my pieces. After a few losses like this I started to get a bad feeling about this knight, and stopped moving it out like that.

Kellie Newsome: I understand how sedatives can get in the way of processing speed, but how to they impair spatial memory and decision making?

Dr. Aiken: There was a study with barbiturate thiopental that illustrates the problem. They gave people low doses of thiopental or a placebo and then had them look at pictures that triggered negative or positive emotions. A negative emotional picture might be of a car accident, and a positive one might be of birds flying or kids playing in the park. On the barbiturate, people had a harder time remembering the emotionally distressing pictures. This makes sense. Like benzodiazepines, barbiturates treat anxiety by turning down the fear response in the amygdala. If you have so much anxiety that everything sends your amygdala into code red this might be helpful, but everyday people they need that anxiety.

Kellie Newsome: Right, because anxiety help us stay alert, and it pushes us to do things. Like if I don’t have any anxiety about my nursing license I’m probably not going to bother renewing it.

Dr. Aiken: Yes, and one thing more. When something makes us anxious we store it away in memory as a bad scene, and in the future we avoid scenes that remind us of it. That’s how we learn from our mistakes. For chess masters, those scenes are the thousands of combinations on the board that are stored in their memory…. So when they see that their king is trapped behind a row of pawns and the other player’s rook is about to swoop down and check mate them, it triggers anxiety and they move one of those pawns up so their king can duck out of the checkmate.

Kellie Newsome: This reminds me of a paper we covered on benzodiazepines last year. It was a meta-analysis of 8 studies that looked at how people read facial emotions while taking benzodiazepines. The benzos made it hard for people to pick up on expressions of anger. They didn’t change recognition of other emotions – just anger, and it was a moderate effect size which means it’s big enough to see in practice. So – I’m speculating here – imagine a patient who’s been on clonazepam for 10 years and he says “I just don’t understand why my wife is so upset at me.” What might be going on is that his wife has been giving him angry looks for years, but he doesn’t pick up on it so he doesn’t learn from his mistakes, and eventually it all blows up into a much bigger marital conflict. 

Dr. Aiken:  Yes that’s exactly the problem that I’m talking about with barbiturates. And we do see it with benzos too. There’s evidence that problem solving abilities decline with long-term benzodiazepine use, and this dampening of the amygdala could be a part of that. When people can’t recognize danger, they are going to make mistakes, and when they don’t feel the pain – the anxiety – from those mistakes they are not going to learn from them. I remember this vividly when I was a resident at Duke and gave a college student a benzo for anxiety. She came back and said, “I feel fine, the anxiety is gone, but the strangest thing is happening: I just don’t care if I miss class or not.”

Kellie Newsome: But there are good reasons to use a benzo. The World Health Organization enumerates those reasons in their report on the Rational Use of Benzodiazepines, including relief of severe anxiety during a short-term crisis. A crisis is a problem that can’t be readily solved.  If there was a clear solution, it wouldn’t be a crisis. One thing that goes wrong for some patients in crises is that their amygdala is so reactive that they jump into frantic solutions, most of which do more harm and good. In DBT we teach people to manage a crisis by “improve the moment” while waiting for it to resolve, and avoiding drastic actions that make it worse. I can see how a benzodiazepine could be part of that plan.

Dr. Aiken: I agree, and if the use it now and then for major crises it’s not going to significantly impair their learning and problem-solving. You just have to watch out for patients who feel like everything is a crisis – whether they lose their keys or lose their job. I tell patients that if they are having a new crisis every 8 hours and taking the benzo constantly like that, they need to come in to talk. We’ve written about the risks – and benefits – of chronic benzo use a lot in the Carlat Report, and my biggest concern is this business with problem-solving skills – because generally the reason these patients are getting so stressed out that their doctor prescribes a benzo is that they don’t have good problem-solving skills to begin with.

The Brain on Chess

Kellie Newsome: So back to chess. You mentioned three things that chess players need: processing speed, visual memory, and decision making skills. Are you pulling this from your own intuition or is there actual research on this?

Dr. Aiken:  Kellie, this is the Carlat Report. Do you think we’d just pull things out of our head without warning the listener? No. This idea comes from two lines of research. First there are psychological studies on which cognitive abilities separate a grand master from an amateur player like myself. That’s how we learned that experienced chess players use visual pattern recognition to guide their play. The other is brain imaging studies, where they place chess masters in a PET scan while they play the game. The areas that light up the most are:

1. The parietal and left frontal lobes, which are involved in spacial tasks.
2. The temporal-parietal junction: which processes of complex visual stimuli
3. The prefrontal cortex and middle temporal area, which generate solutions to complex problems.

There’s also a larger body of research on decision making, and that’s where the connection between the amygdala and the prefrontal cortex lights up. Emotions – the amygdala – are just as important as logic – the frontal lobes – in decision making, which is why people with higher emotional intelligence are better at solving problems.

From Barbiturates to Benzos in The Queen’s Gambit

Kellie Newsome: The Queen’s Gambit follows Beth Harmon, a young girl who learns how to play chess while growing up in a Kentucky orphanage in the 1950’s. It’s also in that orphanage that she encounters barbiturates – which the staff give out at lunchtime to keep the children calm. The barbiturates cause Beth to hallucinate brilliant chess moves. In reality, it’s very rare for barbiturates to cause hallucinations, although hallucinations are a hallmark sign of barbiturate withdrawal. 

But what about this business of orphanages giving barbiturates out to sedate the children? That did happen in the 1950’s, as revealed by a Buzzfeed investigation from 2018. The idea for this plot line also had more personal roots for Walter Tevis, who wrote the novel that the Queen’s Gambit is based on. As a child, Walter spent two years in a convalescent home to recover from rheumatic heart disease, where he was regularly given phenobarbital. 

As Beth comes of age in the 1960’s she switches from barbiturates to a fictional anxiolytic called “Xanzolam” – a contraction of the Xanax and alprazolam. This reflected the real-life shift from barbiturates to benzodiazepines that was ushered in by the release of chlordiazepoxide (Librium) in 1960, and diazepam (Valium) in 1963.

Chess as Therapy

Kellie Newsome: If chess is really a microcosm of human reasoning, is there any evidence that playing chess improves cognition?

Dr. Aiken: Yes it does, but the effects are probably not specific to chess. There is a small controlled trial from France where 26 patients with stable schizophrenia were randomly selected for either chess training or treatment as usual. After 5 weeks, the chess-playing group had some measurable improvements in their executive functioning. They were faster at the Tower of London test, a test of planning ability that requires people to arrange shapes according to rules that limit how they can move the shapes around. They also had better self-control, which is measured by the Stroop test. That’s where they flash cards with the names of colors, and you have to call out the names but the color of the ink is mismatched with the name of the color in order to distract you. So you see the word “Blue” but it’s written in red ink, and you need to suppress your impulse to call out “Red.” The final test they measured was the Wisconsin Card Sort Test, which is one of the most important predictors of real-world functioning. It’s a card game where you have to match cards by color or shape, but the rules of matching keep changing without you knowing it and you have to pick up on that intuitively. So it’s a measure of flexibility – the ability to intuitively adapt to change. There was some evidence of improvement there as well, though that one wasn’t clearly significant. 

Kellie Newsome: You said the study lasted 5 weeks. How much chess did they actually play?

Dr. Aiken: They played for two hours a week, broken up into 2 one hour sessions. The patients played with each other and were guided by a more experienced player who lead the sessions. This is just a small study, but hey it’s harmless, easy, and quite inexpensive to implement.

Kellie Newsome: Harmless? But I’m not so sure that chess is always so harmless. There are rumors about chess masters developing schizophrenia… they touch on that in The Queen’s Gambit too.

Dr. Aiken: Chess does have a tendency to be addictive, and long before video games people worried about young minds getting lost on the chess board. Albert Einstein tried to avoid it for that reason, writing that “Chess holds its master in its own bonds, shackling the mind and brain so that the inner freedom of the very strongest must suffer.” Journalist Bill Hartston had a different opinion, and his famous quote suggests that the causation goes the other way: “Chess doesn’t drive people mad – in fact, it keeps mad people sane.” 

There is evidence of mental benefits from playing board games like chess and its Eastern variants – Go or Shogi. Besides the schizophrenia study, there are studies where these games sharpened cognitive skills in children, reduced symptoms of ADHD and depression, and possibly prevent dementia – although you could find evidence that any activity that is absorbing and challenging has those effects. 

Can Chess Cause Psychosis?

Kellie Newsome: OK but why do so many chess masters have schizophrenia. I looked into this and counted 8, including some of the most prominent figures in chess history. These players rose to the top, only to have their careers derailed by symptoms of psychosis or in some cases a clear diagnosis of schizophrenia. Take Bobby Fisher, the US prodigy who left a dent in the iron curtain when he beat the top Soviet player Boris Spassky in 1972. During that match Fischer started to show signs of psychosis, although with all the cold-war politics that surrounded the tournament it was hard to tell how much of that was reality based. He thought the Soviets were following him and bugging his room, and even trying to control his brain by sending signals through his tooth fillings. He was also extremely distracted by sounds or lights – which is an early sign of schizophrenia – the inability to filter out irrelevant information. 

Dr. Aiken: This is dramatized rather nicely in the 2014 film Pawn Sacrifice. Fisher was 29 years old in 1972, which is at the tail end for onset of schizophrenia. Usually schizophrenia begins in the late teens or early 20’s, but it can begin in the late 20’s and when it does cognition is generally more intact. The late onset give the person time to accomplish things in life before the illness takes hold. 

Kellie Newsome: After his historic win against the Soviets, Bobby Fisher went into hiding. He was sometimes found wandering in the middle of the night, unshaven and disheveled and ranting about Jewish conspiracies. He spent the rest of his life believing that he was being persecuted by an international Jewish group, and that the holocaust was a “a money-making invention.” Now, just because a belief is false does not make it a delusion, and certainly there are subcultures where these kinds of harmful ideas about Jews are normal. But Bobby Fischer did not belong to such a subculture. He was a Jewish boy from New York City. 

Bobby Fischer is just the most famous example of this decline. Paul Morphy, the 19th century champion whose creative energy helped shape modern chess, also developed paranoia and bizarre behavior in his late 20’s. Wilhelm Steinitz, the first world champion, was hospitalized for psychosis – he believed he could play chess against God through a wireless telephone – and this was long before the first cell phone. 

Dr. Aiken: Who won?

Kellie Newsome: Steinitz did.  

Dr. Aiken: So we found 8 chess champions who developed signs of schizophrenia, and nearly all of them were late onset cases. The coincidence is enough that a few researchers have looked for a common cause. So far they’ve found that chess masters are more likely to be born in the winter months, which is a well-known finding in schizophrenia – we think that it’s because virus’ are more common in the winter months, and in utero exposure to a virus can alter brain development in ways that lead to schizophrenia. Left-handedness is also more common in grand masters, now that isn’t saying much as there’s a tendency for very talented people to be left handed, but left-handedness is also more common in schizophrenia. In one study 40% of people with schizophrenia were left-handed, which is 4-times more than the rate in the general population.

Kellie Newsome: What do you think is the connection between schizophrenia and chess ability?

Dr. Aiken: The genes for mental illness often have a positive side. We see that in bipolar disorder, where they bring higher rates of creativity and leadership skills – both in the patients and their relatives. My sense is that schizophrenia also comes with gifts, but that we rarely see the fruits of those strengths because the illness comes on so early and the negative symptoms are so devastating. You’re only going to see those remarkable gifts in late-onset cases, like you do with these chess masters.

Kellie Newsome: Would you also see those strengths in the relatives of people with schizophrenia?

Dr. Aiken: Yes, and I’m not aware of any studies of that but it’s notable that Albert Einstein, the novelists James Joyce, and the philosopher Bertrand Russell all had children with schizophrenia. I talked with Nancy Andreasen about this once. She is a schizophrenia researcher, and she believed that schizophrenia carried with it creative strengths. So she went out to the Iowa Writer’s workshop to look for signs of mental illness in these world-class writers, but what she found was unexpected – there were high rates of bipolar disorder but not of schizophrenia. Still, she thought there was something there, and that people with schizophrenia may have more creative abilities in abstract or scientific fields, which is where the chess connection speculatively fits in. 

Kellie Newsome: So your thinking is that there’s something about the mind in schizophrenia that lends itself to chess talent, rather than that playing too much chess causes schizophrenia.

Dr. Aiken: For the most part, yes, but I wouldn’t recommend tournament chess to prevent schizophrenia. Too much focus on one thing is never good in the long term. Remember in the schizophrenia study they played chess 2 hours a week, not 10 hours a day. There’s also evidence that video games have mental health benefits – but only when played in moderation – the new videogame that the FDA cleared for ADHD shuts off after 20 minutes of play. Competitive chess players also deal with intense physical symptoms of stress during the matches. It’s enough that there are measurable change in their heart rate and blood pressure, and the surges in noradrenaline and corticosteroids that go along with that are not good for the brain.

Chess on Stimulants

Kellie Newsome: Back to your patient – who said that galantamine improved his chess game – has chess ever been used to test the cognitive effects of medications?

Dr. Aiken: Yes there is one from 2017 called “Methylphenidate, modafinil, and caffeine for cognitive enhancement in chess: A double-blind, randomized controlled trial.” It got a lot of press because it came out at the same time that a doping scandal shook the chess world: 1 in 10 tournament chess players in Germany admitted to using cognitive enhancers to improve their game. But let’s take a closer look at the study, because this story gets complex.

Kellie Newsome: They randomized 39 competitive chess players to play against a computer after taking 1 of 3 simulants: methylphenidate (Ritalin) 40 mg, divided into 2 doses, modafinil (Provigil) 400mg or caffeine 400mg – that’ equivalent to 6 shots of espresso and is considered the upper limit of safety for daily caffeine. The players then battled against the computer in a series of 10 games – the games were timed so the human only had 15 minutes to play. The result was that modafinil and methylphenidate caused the players to lose more games because they ran out of time, but when the games that were lost to the clock were eliminated these two stimulants slightly enhanced their play – the effect was equivalent to the advantage the white player has in making the first move – a 5% edge. Caffeine had no effect on performance

Dr. Aiken: That shows how complex things are when you try to use medications to enhance cognition. You may gain in one area, while damaging another. In this case the stimulants made the players think more about their moves, but they deliberated too much, and the expense of the clock. And you need to know about these complexities when fine-tuning stimulants in ADHD. If the dose is too high, the patient may feel over-focused, like they can’t shift out of work mode, they may say they’ve lost their spontaneity, creativity, or – in the case of stand-up comedians I’ve treated – their sense of humor. We’ll cover that in an upcoming issue on stimulants and creativity.

Kellie Newsome: The Queen’s Gambit may have taken some creative license with psychopharmacology, but what about their decision to cast a woman in the role of a chess grandmaster? In our online edition we review the research on gender and chess aptitude.

Article Referenced: “The Queen’s Gambit,” The Carlat Psychiatry Report, January 2021