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Biological basis of schizophrenia

Video transcript

in this video I'm going to talk about the biological basis of schizophrenia schizo free Nia 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 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 let me just write three arrows here the first of these are called cognitive symptoms cognitive 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 negative and these can include things like blunted emotions or a loss of enjoyment in activities the third big category are often called positive symptoms 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 could really can prove 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 positives 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 and 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 farther 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 there 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 topmost part of the brain seems to have decreased size actually 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 frontal and this lobe of the brain which is called the temporal lobe temporal 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 organization of the cerebral cortex cerebral and 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's some disorganization or an abnormal kind of layering of the cells in some of those parts of the cerebral cortex so 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've 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 we have current so a 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 so let me just pull up an image of dopamine so here's an illustration of this molecule called dopamine 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 they used 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 the 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 brainstem 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 sohmas 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 so let me just show one axon here projecting from a ventral tegmental area sending long axon to an area over here in the frontal lobe but it's going to be sending axon all over the cerebrum this other upper part of the brain so this pathway is known by a few names but probably the most common is the mezzo cortical limbic so let me write that down because it's kind of a mouthful mieze Oh cortical limbic mezzo cortical limbic pathway and what the parts of this word mean the first part mezzo refers to the area that the ventral tegmental area is in so this part of the brainstem which just happens we call the midbrain and another term that can be used for that is mezzo so that mezzo 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 to the tempo in that temporal lobe like like we've shown over here and then the limbic part of this term refers to a collection of structures that are kind of that are on the inside of the brain here for the most part it kind of wrap 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 and sometimes people divide up the mezzo cortical limbic pathways into mezzo cortical pathway going from the ventral tegmental area to the frontal and the temporal lobes and a mezzo limbic 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 mesial cortical limbic pathway there does appear to be abnormal activity of the Meisel cortical Olympique pathway it 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 mesial cortical limbic 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 because 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 to schizophrenia can be inherited and there are several genes related to development to 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 and schizophrenia genes may play a role some studies have suggested that certain kinds of physical stress physical stress on the mother during pregnancy such as infections during certain periods of the pregnancy periods it 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 psycho social factors because some studies have suggested a link to things such as a 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 the 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