So, last time, in the last module, I introduced clinically what schizophrenia is. It's a relatively common disorder. 1 out of 100 people in the world are going to suffer this disorder. It has major health and economic and family consequences for them. I don't want to give a misleading picture. Some people do function fairly well with schizophrenia. The treatment is effective for them. But, for a large share of people with schizophrenia, it is a devastating disorder. It reduces their life span. It compromises their health. Today, I will, or in this module I'd like to just highlight a couple interesting features of the epidemiology of schizophrenia, the basic epidemiology. Before we really begit, begin talking about what we might call the genetic epidemiology of schizophrenia, twin and adoption studies. So, I'm going to touch on these four features. Schizophrenia has a rather interesting epidemiology and, of course, epidemiology is the field of science that's interested in the distribution of disease in the population. And I'm going to talk about four features of that distribution and those are highlighted here. So, the first is sex difference and I already talked about this in the previous module. Men who develop schizophrenia tend to develop schizophrenia a little bit earlier than women. One to two years earlier. That doesn't seem like a big difference. But it's a reliable difference. There are other difference between men and women who develop schizophrenia. One is that when men develop schizophrenia, they not only develop it earlier, but they tend to have more severe forms of schizophrenia. And their, because of that their prognosis is poorer than women. A question that's still debated in terms of the epidemiology of schizophrenia is whether men are more likely to develop schizophrenia than women. My own opinion, in reading literature, is that the rates are pretty comparable in men and women. Other people have concluded otherwise, that men are slightly, at a slightly increased risk. I think that's still somewhat of an open question. But regardless of whether men are more likely to develop schizophrenia, when they have schizophrenia they're more likely to have a more severe form with an earlier age of onset. The reason I think that's important is that male greater male vulnerability is characteristic of a whole class of disorders. Disorders that are called neurodevelopmental disorders. You may recall from last time, that when Kraepelin really began talking about what ultimately came to be called schizophrenia, he called it dementia praecox. He thought it was neurodegenerative disorder. But it isn't neurodegenerative like Alzheimer's disease or Parkinson's disease. It's much more like a neurodevelopmental disorder. A neurodegenerative disorder is where you have a, a fully functioning brain that then degenerates over time. A neurodevelopmental disorder is a disorder where there's some affect on neurological development that actually causes, causes the disorder. We know from other research that males are at greater risk for virtually any neurodevelopmental disorder. Not necessarily neurodegenerative disorder. But a neurodevelopmental disorder. Males are at greater risk for autism, they're at greater risk for ADHD, they're at greater risk for intellectual disabilities and learning disabilities. They may not be at greater risk for schizophrenia, but they tend to have more severe forms of schizophrenia. This fits in with, this greater male vulnerability, at least to severity here, fits in with schizophrenia being a neurodevelopmental disorder. Something's happening in the, in the development of the nervous system or the brain that ends up leading the person to develop Schizophrenia. That's the first feature I want to talk about, sex difference. The sex, the second feature of the epidemiology of schizophrenia I'd like to highlight is that schizophrenia is associated with social class. And maybe that's not surprising. This man is, many of you know, John Nash. John Nash won the Nobel prize for actually, research he did as a graduate student in Princeton on game theory. John Nash suffered from, or suffers from schizophrenia. He developed schizophrenia as a, a, a young professor. And actually, there's a, a nice movie about this, called A Beautiful Mind. That talks, he, he, he, he had all these delusional beliefs about the New York Times communicating to him in a code that only he knew about, that the world was going to be invaded by aliens, and that he needed to let the FBI know about this. Obviously, John Nash achieved a lot, I mean, the greatest scientific achievement, he won a Nobel Prize. But there aren't a lot of schizophrenics who achieve. Again, some people with schizophrenia do quite well, but there aren't a lot like John Nash. And we know that schizophrenia's associated with social class, and we know it from a classic study. And the classic study was done 60, 70 years ago I guess by Faris and Dunham and it's, it's such an important study that it launched a whole area of psychiatry called social psychiatry. And what they did is, Faris and Dunham looked at the frequency of schizophrenia in the region of Chicago and that's, this is the Chicago and its outlying suburbs here. And what they plotted here is the frequency of schizophrenia as a function of where you lived in the Chicago region. And what you saw is that what they found was that the, the rate of schizophrenia was much higher in the inner or core city of Chicago, and got progressively less common, the lighter shades, as you move in to the suburbs. Though, so there was association between where you lived and the chance that you had schizophrenia. Now, that might be a social class effect. We know that social class is associated with schizophrenia. And the suburbs are on average, richer, than the core city of Chicago. But if it's a social class effect, we don't necessarily know if it's causal or just correlation. It's a correlation. In fact, it may be that as you begin to develop, recall that you're developing these psychotic symptoms, if you're going to develop schizophrenia in late adolescence, early adulthood. And these symptoms are, can be very devastating to you and to your social achievement, it may be that those symptoms really make it difficult for you to achieve socially in a, in a very competitive culture, as might exist in, in Chicago. So, it may not actually be that social class is causing schizophrenia so much as, as you develop the symptoms, it's hard to maintain high social class and you become poor. That certainly appears to be the case. People have gone back and looked at where the social class of where individuals who develop schizophrenia were born. And it turns out that their social class is unremarkable, if you look at where they're born. They're equally likely to be born to rich parents as to poor parents. So, as they develop the disorder, they lose their social standing, because it's hard to maintain that if you're experiencing these delusional symptoms. There still is something to be explained here, though. And the thought is that maybe living in a densely populated area, in a highly urban environment, might actually contribute to your risk of schizophrenia. This is still an open question in the schiz, in the epidemiology of schizophrenia. But there are some who believe that living in a dense population might contribute to your risk of schizophrenia. It, it might not be a gigantic effect, but it might increase your risk, may, it might double your risk, for example, from 1% to 2%. Why might that be the case? There's some feeling that it might be for psychosocial reasons. Living in a dense population you, you, you might lack social integration that might exist more effectively in less densely populated regions. Another possibility is that urban areas, you might be prone to being exposed to more infectious agents, viral agents. And there are theories of schizophrenia that actually emphasize that it might be actually an infectious disease in part. The third, and actually, somewhat related to this social class urbanicity phenomena feature I want to talk about is the worldwide distribution of schizophrenia. In, a few years ago, the World Health Organization commissioned a study to try to understand, whether or not schizophrenia existed in every culture in the world. And, the conclusion of that study was that it appears that schizophrenia does exist in every culture in the world. Among every ethnic group in the world. And roughly at the same rate. There is some debate as to whether or not your prognosis might be better in some cultures. Agrarian cultures versus others, highly capitalistic cultures, where your prognosis may not be as good. But schizophrenia seem to be roughly, equally distributed across the whole world based on this study. At the same time, there is this kind of interesting observation with schizophrenia, and that is, individuals who migrate, have a higher rates of schizophrenia than individuals who don't migrate. This is a study actually that goes back a long time. It was based on an observation that was done, was made in this state here, in the state of Minnesota. People who were migrating from Denmark at that time, this was back in the early 20th Century to Minnesota, they actually found that they had higher rates of schizophrenia. Now, again, this might be a selective factor. Maybe people who are more likely to develop schizophrenia are more likely to migrate. That seems, it would be pretty remarkable if that's the case, you know, why would people who have this burden be more likely to migrate? It turns out that there's actually no evidence of that. It's not as if people who are more likely to develop the disorder are more likely to migrate. The research doesn't support that. Part of the reason it doesn't support that is, it's not only the first generation of migrants that are at increased risk, it's even the second generation, their children, that are at an increased risk for developing schizophrenia. Again, like urbanicity, the, the effect of the risk isn't that great. It might double your risk. From 1 to 2%, but it's definitely an increase in risk. Why might migration be a risk factor even though the frequency of schizophrenia is uniform across the whole world? Again, there's two thoughts on this. Just like urbanicity. One is it might be psycho-social. People who migrate might be more likely to be discriminated against. That's one hypothesis. The second hypothesis is, again, much like urbanicity. People who migrate might be exposed to viral agents they weren't exposed to in their original countries and that might stimulate schizophrenia. We don't know. There are, again, two possibilities there. The last feature of schizophrenia, and this is actually much more directly related to the genetics of schizophrenia I want to touch on, is fertility. Individuals with schizophrenia have reduced fertility. In fact, they only reproduce at about 40% of the rate of the general population. And if, right, if you understand clinically a little bit about the disorder now, maybe that is not all too surprising. People with schizophrenia are, are not physically infertile. That is not the issue. It's that they have a difficulty establishing and maintaining a relationship long enough, many of them, not all of them for sure, but many of them have difficulty in doing that in order to bring a child, to, to, to, to, to conceive a child and bring a child to birth. And that's why they have a much lower rate of reproduction or fertility. It turns out that the reduction in rate is greater than males than in females with schizophrenia. And again, maybe that's not surprising because males are more likely to have severe forms of schizophrenia. Interestingly, if you look at the first-degree relatives of schi, of individuals with schizophrenia. Those first degree relatives who are not affected with schizophrenia, they don't have this reduction in fertility and that's going to be important in a second here, I'm going to come back to that. Individuals with schizophrenia reproduce at about 40% of the general population. And that actually creates an epidemiological puzzle for those who would have a genetic theory of schizophrenia. Schizophrenia is a common disorder. It affects 1 out 100 of us in the world. It is genetically influenced. We haven't gotten to that. That'll be, we can talk about that next time, but it's also associated with a marked reduction in fertility. If it's a genetically influenced disorder, but yet people with the disorder aren't reproducing, then what should happen over time? It is, would have a selective disadvantage. And so, it should be selected against in the population. And it should become less and less frequent over time, over evolutionary time. While we might imagine that maybe 1% of people have schizophrenia today, maybe if we go back, right, this is, wasn't diagnosed 500 years ago or 1000 years. Maybe it was much more common then. But there really is no evidence of that. And I don't think many people believe that's likely to be the case. There does seem to be a puzzle here. How can it, these three facts don't seem to go together. Another possibility is, well, maybe people with schizophrenia aren't reproducing but their relatives are. Reproducing at a higher rate, but I told you last time that they reproduce at a normal rate. So, they're not replacing those lost genes other as well. So there's a ki, kind of a puzzle here that, that we need to explain and I will explain that next time. How can something be maintained if 1% of the population being affected with it. If it's heritable, but yet selectively disadvantaged. Next time I'm going to take that up after we talk up after we talk about twin and adoption studies. Thank you.
