Biological basis of schizophrenia

- [Voiceover] In this video I'm going to talk about the biological basis of schizophrenia. Schizophrenia which is a common long-term mental disorder that causes a large amount of distress and disability. Schizophrenia is the prototype of the category of mental illness called the "psychotic disorders." Let me just write that. Psychosis, and "psychosis" refers to some specific abnormalities of cognition, and often characteristically abnormal perceptions of reality. These may include hallucinations, which are sensory perceptions without actual stimuli, like hearing or seeing things that aren't actually there, or delusions which are fixed false beliefs not explainable by a person's culture, like if someone has the idea that someone else is controlling their thoughts. The abnormalities of schizophrenia are often divided into three big categories. I'm just going to write three arrows here. The first of these are called "cognitive symptoms." And there can be all sorts of cognitive symptoms with schizophrenia such as abnormalities of attention, organization, or things like planning abilities. The second big category of abnormalities in schizophrenia are often called the "negative symptoms." These can include things like blunted emotions, or a loss of enjoyment in activities. The third big category here often called "positive symptoms," and these are typically the things that we refer to with this term "psychosis." Things like the hallucinations and delusions that are very characteristic of schizophrenia, and the other psychotic disorders, but it really can produce these very complex syndromes spanning many different kind of mental functions from the more thinking type of functions like the cognitive abnormalities, to the more emotional and motivational type functions like the negative symptoms, to the more perceptual abnormalities, these positive symptoms. As of 2014 when I'm making this video our understanding of the cause of schizophrenia is very limited and one reason for that is we have a very limited understanding of how the normal mental functions occur that are abnormal in schizophrenia, but in this video I'll just briefly discuss some of the things that have been noticed about patients with schizophrenia that might play some role in how the disorder develops. First, let me pull up some pictures of the brain to talk about some of the abnormalities that have been seen in the brain with some patients with schizophrenia. So these illustrations are some different ways of looking at the brain because first I want to mention that some brain abnormalities have been observed in some patients with schizophrenia that are visible even without a microscope, even just looking at the brain with the naked eye. One of the first things that was noticed involved these fluid-filled structures inside the brain. I'll just kind of outline a few of them here, and there's another one that we can't see in this view, but in this illustration the brain has been cut with a knife so that we can see the inside of the brain, and there are these little fluid-filled structures here. In some patients with schizophrenia these structures are larger than kind of the population normal. If you averaged out all the people without schizophrenia these can be larger, and there are a few medical conditions that can cause this that don't appear to be happening in schizophrenia, like there doesn't appear to be increased pressure that's pushing these fluid-filled spaces open further than normal. Instead what people think this represents is that the actual amount of brain tissue, if you kind of look at the whole brain tissue that there might be a reduction in the size of all of this brain tissue, so that these fluid-filled spaces are just a little larger than normal because there's less total tissue of the brain. Going along with this idea is that the size of the cerebral cortex, kind of this covering that's on the outside of the cerebrum, the top most part of the brain seems to have decreased size. Actually, it appears to be somewhat thinner, particularly in certain areas of the brain including areas of this lobe of the brain which is called the "frontal lobe," and this lobe of the brain which is called the "temporal lobe," so that some areas of the cortex, the cerebral cortex covering these lobes of the brain appear to have less tissue. They appear to be very subtly thinner in certain spots, and it's been interesting to find these abnormalities in these particular areas of the brain because these areas have a lot to do with cognitive and perceptual functions that are often abnormal in schizophrenia. Now if we take areas of cerebral cortex this layer on the outside of the cerebrum, and we look at it under the microscope like they're showing in this illustration here there's usually kind of an organization to the way the neurons and the other brain cells are organized into layers in the cerebral cortex. Let me just write that out that this is representing the organization of the cerebral cortex. It's often different in the different areas of the cerebral cortex how they're organized, so these are just a few examples of how the cells in the cortex may be organized, and what's been seen in some patients with schizophrenia is that the normal organization of these cortical layers, particularly in these areas of the frontal and temporal lobes that have been seen in some patients to be thinner and have less tissue there is some disorganization, or an abnormal kind of layering of the cells in some of those parts of the cerebral cortex. These are some of the physical differences that have been seen in some patients with schizophrenia either when their brains have been examined at autopsy after they have passed away, or with special scans that can look at the structures of the brain, but now there are newer kinds of scans that can actually look at the activity in different areas of the brain, and some studies that have been looking at these scans have also noticed in areas of the frontal and temporal lobes in some of these same areas that the structural abnormalities have been seen. There appears to be a signal that there may be abnormal activity on the kinds of functional scans that we have currently, so the likely possibility is that in patients who develop schizophrenia, something happens abnormally during development of the brain, and that these particular areas of the brain do not develop normally leading to the disease. Some features of schizophrenia, though, also appear to involve abnormalities in a neuronal pathway that uses dopamine as a neurotransmitter. Let me just pull up an image of dopamine. Here's an illustration of this molecule called "dopamine," which is an important neurotransmitter in the nervous system that communicates lots of information between neurons and parts of the brain, and the networks of neurons that use dopamine appear to influence activity in different areas of the brain, so that abnormalities can cause abnormal activities in certain parts of the brain, and importantly for schizophrenia dopamine appears to play a big role in the activity of the frontal, and the temporal lobes of the brain, and particularly areas of cerebral cortex in the frontal and temporal lobes that play major roles in many of the cognitive, emotional and perceptual functions that are often abnormal in schizophrenia, and supporting the idea that dopamine, or abnormalities of dopamine in the brain may be playing a role in schizophrenia is the fact that a number of medications that affect dopamine neurotransmission often improve many of the symptoms of schizophrenia. One pathway, in particular, has attracted a lot of attention as likely playing a role in schizophrenia. There are a collection of neurons right around here in the brain stem that use dopamine as their neurotransmitter, so that their somas or cell bodies are located in this area of the brainstem, and that area is called the "ventral tegmental" area. I'll just write VTA, for short, for ventral tegmental area. That's where the somas of these neurons that are going to use dopamine are located, and then their axons project to a number of areas throughout the brain to release that dopamine onto other neurons in many areas of the brain. Let me just show one axon here projecting from the ventral tegmental area sending a long axon to an area over here in the frontal lobe, but it's going to be sending axons all over the cerebrum this upper part of the brain. This pathway is known by a few names, but probably the most common is the "mesocorticolimbic." Let me write that down because it's kind of a mouthful. Mesocorticolimbic. Mesocorticolimbic pathway, and what the parts of this word mean, the first part "meso" refers to the area that the ventral tegmental area is in. So this part of the brainstem, which happens to be called the midbrain, and another term that can be used for that is "meso," so that meso refers to where these neurons are starting in the midbrain. The "cortical" refers to the cerebral cortex, and many of these axons are projecting to areas of the frontal cortex, the cerebral cortex of the frontal lobe like we've shown over here, and also areas of cerebral cortex in the temporal lobe like we've shown over here. Then the "limbic" part of this term refers to a collection of structures that are on the inside of the brain here for the most part, it kind of wraps around this inside part of the brain here. If you've cut the brain in between the right and the left halves of the cerebral hemispheres, and these limbic areas of the brain are very involved in emotions, motivation, and a number of other brain functions. Sometimes people divide up the mesocorticolimbic pathways into mesococortical pathway going from the ventral tegmental area to the frontal and the temporal lobes, in a mesolimbic pathway going from the ventral tegmental area to these limbic structures, but a lot of times people lump it together, and call it one pathway, the "mesocorticolimbic pathway." There does appear to be abnormal activity of the mesocorticolimbic pathway that carries dopamine from the ventral tegmental area to these areas of cerebral cortex. One way of thinking about schizophrenia which is surely incomplete at best, but that is a nice way to think about it is that abnormal activity in the mesocorticolimbic pathway leads to dysfunction in parts of the frontal cortex that cause many, if not most, of the cognitive symptoms of schizophrenia. Abnormal activity in parts of the limbic structures that cause many, if not most, of the negative symptoms of schizophrenia, and abnormal activity in parts of the temporal cortex that might cause many, if not most, of the positive symptoms. In reality, however, abnormalities that are involved appear to be far more complex than this simple idea, and there's likely widespread dysfunction of many neuronal networks, and multiple neurotransmitter systems throughout many different areas of the brain. So those are some of the biological things that have been seen in studies of patients with schizophrenia. The last couple of things I want to mention before I finish this short video is that there are a number of clues that multiple kinds of things may be involved in causing the brain abnormalities responsible for schizophrenia. Genetic studies have suggested that a predisposition of schizophrenia can be inherited and there are several genes related to development of the brain, or brain function that have been associated with the risk of the disease. It may be that genetic abnormalities increase the risk of the brain developing abnormally in certain situations, so when it comes to looking for causes of the abnormalities we see in the structure, and function of the brain in schizophrenia genes may play a role. Some studies have suggested that certain kinds of physical stress on the mother during pregnancy such as infections during certain periods of the pregnancy, periods that might be critical for development of the brain. These physical stresses during the pregnancy may increase the risk of schizophrenia, and it does appear that psychosocial factors may play a role as well. Psychosocial factors because some studies have suggested a link to things such as negative interpersonal, or family interaction styles during childhood because the neuronal networks of the brain continue to develop after birth in response to life experiences, so it may be that negative life experiences early when the brain is still wiring itself may play some role in some cases of schizophrenia. There's also an association of schizophrenia, and poverty that's very poorly understood, and it's unclear if poverty could contribute to the causes of the disorder, or if people and families at risk for schizophrenia tend toward poverty due to the mental disability of the disease itself.