WEBVTT
00:00:00.080 --> 00:00:05.360
Though I think this is a very important story in psychiatry's history, it's a story I was totally unfamiliar with.
00:00:05.519 --> 00:00:06.719
It follows Dr.
00:00:06.799 --> 00:00:15.759
Solomon Snyder, whose experiments with mind-altering drugs helped change the way we think about the causes and treatments of schizophrenia.
00:00:16.000 --> 00:00:20.160
What did he discover with his experiments using amphetamines?
00:00:20.480 --> 00:00:25.600
I mean, we've always known that there was a connection between amphetamine use and psychosis.
00:00:25.760 --> 00:00:45.920
So in the 1930s, 1940s, a lot of people were using amphetamines, and some people, a very small minority, were having psychotic episodes that looked almost exactly like schizophrenia, like auditory hallucinations, paranoid uh delusions.
00:00:46.079 --> 00:01:04.560
But doctors were pretty much able to kind of brush that under the carpet, again, because it was rare, and they thought, well, it's probably mainly drug addicts who are experiencing psychosis, not people who are just using amphetamines uh at their prescribed uh doses for appropriate clinical purposes.
00:01:04.799 --> 00:01:16.560
But by the 1960s, what happened is that you had a whole drug subculture in the United States that was built around injecting speed directly.
00:01:16.719 --> 00:01:20.719
And so they were drug subculture was known as the speed freaks.
00:01:21.040 --> 00:01:39.760
I don't know if they called themselves speed freaks or other people called them uh speed freaks, but they were taking far, far greater quantities of amphetamines uh than any of the artists and writers of the 1940s, 1950s, like Andy Warhol or Jack Kerouac.
00:01:39.920 --> 00:01:49.359
You know, they liked taking amphetamines, but they they that was like child's play compared to the levels that the that the what they called the speed freaks were taking.
00:01:49.439 --> 00:02:07.439
Uh, but what would often happen is that after somebody was injecting speed, usually over, you know, two to three to four days at a time, they would often enough develop uh an episode that was almost identical to paranoid schizophrenia.
00:02:07.599 --> 00:02:13.840
They were routinely misdiagnosed with doctors as having uh paranoid schizophrenia.
00:02:14.000 --> 00:02:30.319
And so coming back around to uh Snyder, there was another psych, there was a psychiatrist in New York, Burton Engrist, who is fascinated with the power of amphetamines to induce a schizophrenia-like state.
00:02:30.479 --> 00:02:38.479
And he, in order to demonstrate that amphetamines could do this, he actually got together uh a number of volunteers.
00:02:38.560 --> 00:02:42.560
Uh then they were all recreational speed users from New York.
00:02:43.360 --> 00:02:51.680
He brought them to Bellevue Psychiatric Hospital, and he literally gave them amphetamines until they became psychotic.
00:02:51.840 --> 00:03:13.520
So he would give them, you know, 10 milligrams an hour later, another 10 milligrams an hour later, another 10 milligrams, and he found that within about 20 hours he could induce auditory hallucinations, delusions, sometimes thought disorder, this kind of complete fragmentation of logic.
00:03:14.000 --> 00:03:38.240
And so when Solomon Snyder encountered Burton Angrist's work and saw that you could reproduce something that was so similar to schizophrenia using amphetamines, uh, that's what he decided he wanted to study, that he was wrong about LSD and amphetamines, uh, this was the tool that he needed.
00:03:38.719 --> 00:03:41.599
And so you asked what he discovered.
00:03:42.000 --> 00:03:50.159
What he was interested in this uh uh in was this how exactly do amphetamines bring about psychosis?
00:03:50.400 --> 00:03:58.639
So he knew that amphetamines uh impact a number of different neurotransmitter systems like dopamine and noradrenaline.
00:03:58.800 --> 00:04:07.120
And he wanted to know, okay, which one of those neurotransmitter systems is primarily connected with uh psychosis.
00:04:07.360 --> 00:04:13.120
So in uh, I believe in 1970, he did some pretty ingenious research with rats.
00:04:13.280 --> 00:04:19.519
I mean, debatable what he what conclusions he could draw, but it was fairly ingenious research.
00:04:19.680 --> 00:04:27.439
And it convinced him that amphetamines induce psychosis by flooding the brain with dopamine.
00:04:28.000 --> 00:04:44.319
And that in 1970 is what really woke him up to the dopamine hypothesis of schizophrenia, or at least an early version of that, namely, uh, what if schizophrenia itself is just a disease of excessive uh dopamine?
00:04:44.480 --> 00:04:51.680
And then he spent the next five or six years pursuing that trail, and that's how he got the dopamine hypothesis.
00:04:52.000 --> 00:04:55.759
And I would add, just from my own clinical experience, I totally agree.
00:04:55.920 --> 00:05:10.079
And a psychosis that's kind of a more typical schizophrenia without drugs, is in my experience clinically indistinguishable from a psychosis that someone gets from heavy cannabis use, heavy amphetamine use.
00:05:10.319 --> 00:05:25.040
We have had I've seen many cases of patients, for example, uh coming to a psychiatric ward with like a full-on psychotic episode, and then they stay off, for example, cannabis for three days and they go completely back to baseline.
00:05:25.279 --> 00:05:29.600
So totally makes sense that then he would follow the path to studying amphetamines.
00:05:29.759 --> 00:05:35.519
What was, how did he figure out in rats that dopamine was implicated that it was a flooding of dopamine?
00:05:35.680 --> 00:05:38.480
Was it kind of radioactive uh isotopes?
00:05:39.360 --> 00:05:47.759
Well, it's a little bit complicated, but he he he he knew that amphetamines come in these two slightly different forms or what they call isomers.
00:05:47.839 --> 00:05:52.000
There's the levoamphetamine and there's the dextroamphetamine.
00:05:52.399 --> 00:06:07.040
And he knew that dextroamphetamine, that's the one that really associated with central nervous system stimulation, getting focused, getting, you know, energized, uh, having a lot of ideas and a lot of uh uh projects.
00:06:07.199 --> 00:06:25.360
And so he knew that the dextroamphetamine was more closely connected with the central nervous system stimulation and less closely connected with the psychosis or the behavior in rats that he thought resembled psychosis, namely the stereotyped uh behavior.
00:06:25.920 --> 00:06:39.439
Whereas he realized that uh levoamphetamine seemed to be much more closely associated with this psychosis-like behavior and less associated with the central nervous system stimulation.
00:06:39.600 --> 00:06:59.360
So through a fairly indirect uh path of reasoning, he thought, okay, uh what neurotransmitter system is levoamphetamine uh interacting with that the dexteroamphetamine is not so much, and that's what led him to uh uh dopamine.
00:06:59.759 --> 00:07:14.399
And so it's you know, I mean, even at the time it was contested a bit, um, partly because is this a valid animal model of psychosis, stereotyped behavior in rats?
00:07:14.480 --> 00:07:17.199
But that's how he he he got to that conclusion.
00:07:17.600 --> 00:07:22.639
And then was that did he then continue his research onto human subjects after that?
00:07:23.120 --> 00:07:26.160
He did not, uh, though Burton Angrist did.
00:07:26.240 --> 00:07:52.079
He was inspired by um Solomon Snyder's research, and so he decided to do a similar uh kind of experiment with humans, where he divided up his volunteers into two groups, and I think he gave some levoamphetamine and he gave others dextroamphetamine, and he found uh I mean he really had a very small population, so I don't know what we can really draw from that.
00:07:52.160 --> 00:07:59.439
But he did find that the levoamphetamine seemed to be more closely associated with uh uh psychosis.
00:07:59.680 --> 00:08:18.959
No, for Solomon Snyder, his main question, once he had come to this conclusion that uh amphetamines could trigger psychosis by flooding the brain with dopamine, uh, that led him to his next question, which was okay, how do antipsychotic drugs work?
00:08:19.120 --> 00:08:22.160
Because he had this picture in his mind, something like this.
00:08:23.120 --> 00:08:31.759
Suppose that antipsychotic drugs like chlorpromazine and HALDOL, suppose they work by blocking dopamine receptors.
00:08:31.920 --> 00:08:43.519
Then I have this simple, beautiful picture where if I flood your brain with dopamine, I can induce schizophrenia or a schizophrenic uh schizophrenia-like state.
00:08:44.000 --> 00:08:50.879
If I block dopamine activity, I can alleviate this schizophrenia state.
00:08:51.039 --> 00:08:58.240
And so by turning dopamine on and off, it's almost as if I can turn psychosis uh on and off.
00:08:58.399 --> 00:09:15.679
And so after the amphetamine research, uh all of a lot of his research was focused on understanding exactly what antipsychotic drugs did to the brain, which interestingly enough, even in 1970, was not entirely known.
00:09:15.919 --> 00:09:22.799
People did theorize that there was some connection between drugs like chloropromazine and uh dopamine.
00:09:23.120 --> 00:09:30.480
Many people uh suspected that these drugs worked by blocking dopamine receptors, but there was some mixed evidence.
00:09:30.639 --> 00:09:41.440
There was some evidence that while perhaps chloropromazine was a dopamine blocker, maybe haloperidol had some completely different mechanism uh uh of action.
00:09:41.600 --> 00:09:46.960
So it really wasn't settled until some of the research that he did in the in the early 70s.
00:09:47.279 --> 00:09:49.360
So he conclusively proved it.
00:09:49.519 --> 00:09:58.159
And then would you say that's fundamentally where the dopamine hypothesis for schizophrenia comes from, primarily from his work, would you say?
00:09:58.879 --> 00:10:00.159
I I believe it does.
00:10:00.320 --> 00:10:08.720
I I well I think that the dopamine hypothesis of schizophrenia is really based on these two main pillars of evidence.
00:10:08.879 --> 00:10:14.000
It certainly uh was in the in the 1970s, in the mid-1970s.
00:10:14.159 --> 00:10:21.840
The one pillar of evidence is that was that amphetamines seemed to trigger psychosis by flooding the brain with dopamine.
00:10:22.159 --> 00:10:30.320
And the other pillar of evidence being that it seems that we can alleviate symptoms of schizophrenia by blocking your dopamine.
00:10:30.639 --> 00:10:38.879
Again, giving rise to this simple intuitive picture that by turning dopamine on and off, I can turn uh psychosis on and off.
00:10:39.039 --> 00:10:46.639
There were other people at the so he wrote this paper, the dopamine hypothesis of schizophrenia, in 1976.
00:10:46.879 --> 00:10:48.799
Uh, it was very influential.
00:10:49.120 --> 00:11:10.559
A few other people were writing papers that were similar on the role of dopamine in schizophrenia, but a lot of the research they were relying on was Solomon Snyder's research with amphetamines, and certainly his research uh proving conclusively that these uh early antipsychotic drugs worked by blocking dopamine.
00:11:10.879 --> 00:11:16.480
So even the the other people writing about it were were inspired and motivated by his research.
00:11:16.799 --> 00:11:36.240
And I'm imagining this must be a huge deal for the psychiatric community at the time because this is finally giving some biological credence to a major cause of mental illness, giving doctors, you know, doctors love tangible things, giving doctors tangible mechanisms, explaining how and why the medications work.
00:11:36.399 --> 00:11:42.159
So, what was the reaction of the psychiatric community at the time to these revelations?
00:11:42.799 --> 00:11:44.960
I think you're exactly right.
00:11:45.120 --> 00:11:52.080
It was a simple, beautiful picture that a lot of psychiatrists just latched on to.
00:11:52.320 --> 00:12:10.159
And, you know, as you know, there were biological psychiatrists uh before the 1970s and the 1950s and 1960s, with the idea that schizophrenia or depression or bipolar disorder probably has its roots in a neurotransmitter imbalance.
00:12:10.320 --> 00:12:20.080
But that remained kind of theoretical, hypothetical, and it and it um they didn't really have compelling evidence on their side.
00:12:20.320 --> 00:12:41.519
So one way I read the dopamine hypothesis of schizophrenia paper is finally giving psychiatry what seemed to be strong evidence that schizophrenia could be explained in terms of a single uh neurotransmitter imbalance.
00:12:41.679 --> 00:12:46.720
Solomon Snyder was very clear, incidentally, uh, right at the outset of the paper.
00:12:46.879 --> 00:12:50.799
He said, look, all of this evidence is ultimately indirect.
00:12:50.960 --> 00:13:06.879
We don't have evidence uh that there are actual dopamine abnormalities in patients who have been diagnosed with schizophrenia and particularly diagnosed with schizophrenia uh and who have not been on these antipsychotic uh drugs.
00:13:07.279 --> 00:13:19.200
But he put together the indirect evidence into such a compelling picture that I think a lot of psychiatrists considered it to be almost as if he had given them smoking gun evidence.
00:13:19.360 --> 00:13:25.600
And I love the way that the historian Ann Harrington, she has a wonderful book called Mind Fixers.
00:13:25.840 --> 00:13:38.240
And I think she puts it like this the dopamine hypothesis helped schizophrenia become the poster child disorder for the new biological orthodoxy in psychiatry.
00:13:38.480 --> 00:13:43.600
So it really was, I think it functioned as a poster child in that way.
00:13:43.840 --> 00:13:59.519
It got a lot of uh uh researchers very interested in using the emerging neuroimaging technologies to try to locate the actual uh dopamine dysfunction in the brains of uh patients.
00:13:59.759 --> 00:14:09.360
I think it also gave rise in the 1980s and 1990s to a lot of like copycat chemical imbalance theories.
00:14:09.440 --> 00:14:23.600
It was like, well, the dopamine hypothesis was so successful, now we're going to promote the serotonin hypothesis of depression, or now we're going to promote the noradrenaline hypothesis of ADHD.
00:14:23.759 --> 00:14:35.919
So I think it really helped to um solidify this much larger paradigm that sees mental disorders in terms of uh neurotransmitter imbalances.
00:00:00.080 --> 00:00:05.360
Though I think this is a very important story in psychiatry's history, it's a story I was totally unfamiliar with.
00:00:05.519 --> 00:00:06.719
It follows Dr.
00:00:06.799 --> 00:00:15.759
Solomon Snyder, whose experiments with mind-altering drugs helped change the way we think about the causes and treatments of schizophrenia.
00:00:16.000 --> 00:00:20.160
What did he discover with his experiments using amphetamines?
00:00:20.480 --> 00:00:25.600
I mean, we've always known that there was a connection between amphetamine use and psychosis.
00:00:25.760 --> 00:00:45.920
So in the 1930s, 1940s, a lot of people were using amphetamines, and some people, a very small minority, were having psychotic episodes that looked almost exactly like schizophrenia, like auditory hallucinations, paranoid uh delusions.
00:00:46.079 --> 00:01:04.560
But doctors were pretty much able to kind of brush that under the carpet, again, because it was rare, and they thought, well, it's probably mainly drug addicts who are experiencing psychosis, not people who are just using amphetamines uh at their prescribed uh doses for appropriate clinical purposes.
00:01:04.799 --> 00:01:16.560
But by the 1960s, what happened is that you had a whole drug subculture in the United States that was built around injecting speed directly.
00:01:16.719 --> 00:01:20.719
And so they were drug subculture was known as the speed freaks.
00:01:21.040 --> 00:01:39.760
I don't know if they called themselves speed freaks or other people called them uh speed freaks, but they were taking far, far greater quantities of amphetamines uh than any of the artists and writers of the 1940s, 1950s, like Andy Warhol or Jack Kerouac.
00:01:39.920 --> 00:01:49.359
You know, they liked taking amphetamines, but they they that was like child's play compared to the levels that the that the what they called the speed freaks were taking.
00:01:49.439 --> 00:02:07.439
Uh, but what would often happen is that after somebody was injecting speed, usually over, you know, two to three to four days at a time, they would often enough develop uh an episode that was almost identical to paranoid schizophrenia.
00:02:07.599 --> 00:02:13.840
They were routinely misdiagnosed with doctors as having uh paranoid schizophrenia.
00:02:14.000 --> 00:02:30.319
And so coming back around to uh Snyder, there was another psych, there was a psychiatrist in New York, Burton Engrist, who is fascinated with the power of amphetamines to induce a schizophrenia-like state.
00:02:30.479 --> 00:02:38.479
And he, in order to demonstrate that amphetamines could do this, he actually got together uh a number of volunteers.
00:02:38.560 --> 00:02:42.560
Uh then they were all recreational speed users from New York.
00:02:43.360 --> 00:02:51.680
He brought them to Bellevue Psychiatric Hospital, and he literally gave them amphetamines until they became psychotic.
00:02:51.840 --> 00:03:13.520
So he would give them, you know, 10 milligrams an hour later, another 10 milligrams an hour later, another 10 milligrams, and he found that within about 20 hours he could induce auditory hallucinations, delusions, sometimes thought disorder, this kind of complete fragmentation of logic.
00:03:14.000 --> 00:03:38.240
And so when Solomon Snyder encountered Burton Angrist's work and saw that you could reproduce something that was so similar to schizophrenia using amphetamines, uh, that's what he decided he wanted to study, that he was wrong about LSD and amphetamines, uh, this was the tool that he needed.
00:03:38.719 --> 00:03:41.599
And so you asked what he discovered.
00:03:42.000 --> 00:03:50.159
What he was interested in this uh uh in was this how exactly do amphetamines bring about psychosis?
00:03:50.400 --> 00:03:58.639
So he knew that amphetamines uh impact a number of different neurotransmitter systems like dopamine and noradrenaline.
00:03:58.800 --> 00:04:07.120
And he wanted to know, okay, which one of those neurotransmitter systems is primarily connected with uh psychosis.
00:04:07.360 --> 00:04:13.120
So in uh, I believe in 1970, he did some pretty ingenious research with rats.
00:04:13.280 --> 00:04:19.519
I mean, debatable what he what conclusions he could draw, but it was fairly ingenious research.
00:04:19.680 --> 00:04:27.439
And it convinced him that amphetamines induce psychosis by flooding the brain with dopamine.
00:04:28.000 --> 00:04:44.319
And that in 1970 is what really woke him up to the dopamine hypothesis of schizophrenia, or at least an early version of that, namely, uh, what if schizophrenia itself is just a disease of excessive uh dopamine?
00:04:44.480 --> 00:04:51.680
And then he spent the next five or six years pursuing that trail, and that's how he got the dopamine hypothesis.
00:04:52.000 --> 00:04:55.759
And I would add, just from my own clinical experience, I totally agree.
00:04:55.920 --> 00:05:10.079
And a psychosis that's kind of a more typical schizophrenia without drugs, is in my experience clinically indistinguishable from a psychosis that someone gets from heavy cannabis use, heavy amphetamine use.
00:05:10.319 --> 00:05:25.040
We have had I've seen many cases of patients, for example, uh coming to a psychiatric ward with like a full-on psychotic episode, and then they stay off, for example, cannabis for three days and they go completely back to baseline.
00:05:25.279 --> 00:05:29.600
So totally makes sense that then he would follow the path to studying amphetamines.
00:05:29.759 --> 00:05:35.519
What was, how did he figure out in rats that dopamine was implicated that it was a flooding of dopamine?
00:05:35.680 --> 00:05:38.480
Was it kind of radioactive uh isotopes?
00:05:39.360 --> 00:05:47.759
Well, it's a little bit complicated, but he he he he knew that amphetamines come in these two slightly different forms or what they call isomers.
00:05:47.839 --> 00:05:52.000
There's the levoamphetamine and there's the dextroamphetamine.
00:05:52.399 --> 00:06:07.040
And he knew that dextroamphetamine, that's the one that really associated with central nervous system stimulation, getting focused, getting, you know, energized, uh, having a lot of ideas and a lot of uh uh projects.
00:06:07.199 --> 00:06:25.360
And so he knew that the dextroamphetamine was more closely connected with the central nervous system stimulation and less closely connected with the psychosis or the behavior in rats that he thought resembled psychosis, namely the stereotyped uh behavior.
00:06:25.920 --> 00:06:39.439
Whereas he realized that uh levoamphetamine seemed to be much more closely associated with this psychosis-like behavior and less associated with the central nervous system stimulation.
00:06:39.600 --> 00:06:59.360
So through a fairly indirect uh path of reasoning, he thought, okay, uh what neurotransmitter system is levoamphetamine uh interacting with that the dexteroamphetamine is not so much, and that's what led him to uh uh dopamine.
00:06:59.759 --> 00:07:14.399
And so it's you know, I mean, even at the time it was contested a bit, um, partly because is this a valid animal model of psychosis, stereotyped behavior in rats?
00:07:14.480 --> 00:07:17.199
But that's how he he he got to that conclusion.
00:07:17.600 --> 00:07:22.639
And then was that did he then continue his research onto human subjects after that?
00:07:23.120 --> 00:07:26.160
He did not, uh, though Burton Angrist did.
00:07:26.240 --> 00:07:52.079
He was inspired by um Solomon Snyder's research, and so he decided to do a similar uh kind of experiment with humans, where he divided up his volunteers into two groups, and I think he gave some levoamphetamine and he gave others dextroamphetamine, and he found uh I mean he really had a very small population, so I don't know what we can really draw from that.
00:07:52.160 --> 00:07:59.439
But he did find that the levoamphetamine seemed to be more closely associated with uh uh psychosis.
00:07:59.680 --> 00:08:18.959
No, for Solomon Snyder, his main question, once he had come to this conclusion that uh amphetamines could trigger psychosis by flooding the brain with dopamine, uh, that led him to his next question, which was okay, how do antipsychotic drugs work?
00:08:19.120 --> 00:08:22.160
Because he had this picture in his mind, something like this.
00:08:23.120 --> 00:08:31.759
Suppose that antipsychotic drugs like chlorpromazine and HALDOL, suppose they work by blocking dopamine receptors.
00:08:31.920 --> 00:08:43.519
Then I have this simple, beautiful picture where if I flood your brain with dopamine, I can induce schizophrenia or a schizophrenic uh schizophrenia-like state.
00:08:44.000 --> 00:08:50.879
If I block dopamine activity, I can alleviate this schizophrenia state.
00:08:51.039 --> 00:08:58.240
And so by turning dopamine on and off, it's almost as if I can turn psychosis uh on and off.
00:08:58.399 --> 00:09:15.679
And so after the amphetamine research, uh all of a lot of his research was focused on understanding exactly what antipsychotic drugs did to the brain, which interestingly enough, even in 1970, was not entirely known.
00:09:15.919 --> 00:09:22.799
People did theorize that there was some connection between drugs like chloropromazine and uh dopamine.
00:09:23.120 --> 00:09:30.480
Many people uh suspected that these drugs worked by blocking dopamine receptors, but there was some mixed evidence.
00:09:30.639 --> 00:09:41.440
There was some evidence that while perhaps chloropromazine was a dopamine blocker, maybe haloperidol had some completely different mechanism uh uh of action.
00:09:41.600 --> 00:09:46.960
So it really wasn't settled until some of the research that he did in the in the early 70s.
00:09:47.279 --> 00:09:49.360
So he conclusively proved it.
00:09:49.519 --> 00:09:58.159
And then would you say that's fundamentally where the dopamine hypothesis for schizophrenia comes from, primarily from his work, would you say?
00:09:58.879 --> 00:10:00.159
I I believe it does.
00:10:00.320 --> 00:10:08.720
I I well I think that the dopamine hypothesis of schizophrenia is really based on these two main pillars of evidence.
00:10:08.879 --> 00:10:14.000
It certainly uh was in the in the 1970s, in the mid-1970s.
00:10:14.159 --> 00:10:21.840
The one pillar of evidence is that was that amphetamines seemed to trigger psychosis by flooding the brain with dopamine.
00:10:22.159 --> 00:10:30.320
And the other pillar of evidence being that it seems that we can alleviate symptoms of schizophrenia by blocking your dopamine.
00:10:30.639 --> 00:10:38.879
Again, giving rise to this simple intuitive picture that by turning dopamine on and off, I can turn uh psychosis on and off.
00:10:39.039 --> 00:10:46.639
There were other people at the so he wrote this paper, the dopamine hypothesis of schizophrenia, in 1976.
00:10:46.879 --> 00:10:48.799
Uh, it was very influential.
00:10:49.120 --> 00:11:10.559
A few other people were writing papers that were similar on the role of dopamine in schizophrenia, but a lot of the research they were relying on was Solomon Snyder's research with amphetamines, and certainly his research uh proving conclusively that these uh early antipsychotic drugs worked by blocking dopamine.
00:11:10.879 --> 00:11:16.480
So even the the other people writing about it were were inspired and motivated by his research.
00:11:16.799 --> 00:11:36.240
And I'm imagining this must be a huge deal for the psychiatric community at the time because this is finally giving some biological credence to a major cause of mental illness, giving doctors, you know, doctors love tangible things, giving doctors tangible mechanisms, explaining how and why the medications work.
00:11:36.399 --> 00:11:42.159
So, what was the reaction of the psychiatric community at the time to these revelations?
00:11:42.799 --> 00:11:44.960
I think you're exactly right.
00:11:45.120 --> 00:11:52.080
It was a simple, beautiful picture that a lot of psychiatrists just latched on to.
00:11:52.320 --> 00:12:10.159
And, you know, as you know, there were biological psychiatrists uh before the 1970s and the 1950s and 1960s, with the idea that schizophrenia or depression or bipolar disorder probably has its roots in a neurotransmitter imbalance.
00:12:10.320 --> 00:12:20.080
But that remained kind of theoretical, hypothetical, and it and it um they didn't really have compelling evidence on their side.
00:12:20.320 --> 00:12:41.519
So one way I read the dopamine hypothesis of schizophrenia paper is finally giving psychiatry what seemed to be strong evidence that schizophrenia could be explained in terms of a single uh neurotransmitter imbalance.
00:12:41.679 --> 00:12:46.720
Solomon Snyder was very clear, incidentally, uh, right at the outset of the paper.
00:12:46.879 --> 00:12:50.799
He said, look, all of this evidence is ultimately indirect.
00:12:50.960 --> 00:13:06.879
We don't have evidence uh that there are actual dopamine abnormalities in patients who have been diagnosed with schizophrenia and particularly diagnosed with schizophrenia uh and who have not been on these antipsychotic uh drugs.
00:13:07.279 --> 00:13:19.200
But he put together the indirect evidence into such a compelling picture that I think a lot of psychiatrists considered it to be almost as if he had given them smoking gun evidence.
00:13:19.360 --> 00:13:25.600
And I love the way that the historian Ann Harrington, she has a wonderful book called Mind Fixers.
00:13:25.840 --> 00:13:38.240
And I think she puts it like this the dopamine hypothesis helped schizophrenia become the poster child disorder for the new biological orthodoxy in psychiatry.
00:13:38.480 --> 00:13:43.600
So it really was, I think it functioned as a poster child in that way.
00:13:43.840 --> 00:13:59.519
It got a lot of uh uh researchers very interested in using the emerging neuroimaging technologies to try to locate the actual uh dopamine dysfunction in the brains of uh patients.
00:13:59.759 --> 00:14:09.360
I think it also gave rise in the 1980s and 1990s to a lot of like copycat chemical imbalance theories.
00:14:09.440 --> 00:14:23.600
It was like, well, the dopamine hypothesis was so successful, now we're going to promote the serotonin hypothesis of depression, or now we're going to promote the noradrenaline hypothesis of ADHD.
00:14:23.759 --> 00:14:35.919
So I think it really helped to um solidify this much larger paradigm that sees mental disorders in terms of uh neurotransmitter imbalances.
