- [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.