Hello everyone, and welcome back. In our last section, we began talking
about the types of disorders and we talked about cerebral vascular disorders
(or what are called strokes). In this section we begin talking about a
second major group of disorders commonly called schizophrenia. So letís
begin by looking at a little bit of an overview of schizophrenia on page
First of all, schizophrenia probably consists
of more than one general disorder. However, it is the most devastating
disorder that we have. It occurs about in 1% of the population and really
there are no major sex differences in prevalence rates. However, the cost
for care of individuals with schizophrenia tops 30 billion dollars annually,
and thatís just in the United States. In addition, many individuals stop
taking the medications or are untreated. As a result of the symptoms they
usually become homeless.
Generally schizophrenia is considered to be a disorder of
thought or emotion. However, itís not a split personality disorder.
Schizophrenia, though, is (as we see in slide three) characterized by
several things; disorganized thoughts, hallucinations, delusions and bizarre
behaviors. There are also (as we see in slide four) two different groups or
types of schizophrenic symptoms; positive symptoms and negative symptoms.
Often these symptoms, which weíll talk about in a minute, are preceded by
what we call prodromal signs. These include things such as social
isolation, the person starts behaving a little bit weird or they get odd
behavior and ideas, their hygiene becomes poorer, and they get what is
called a blunted affect, which is in essence where you just seem to have no
So, letís talk about positive symptoms first (these
positive symptoms are shown in slide five). Usually positive symptoms occur
during psychotic episodes and they usually involve very distinct abnormal
behaviors. These include things such as delusions, hallucinations and
disturbances in the form of thought. So what are delusions? Well,
delusions, as we see in slide six, are beliefs that are contrary to
reality. They can involve control delusions, grandeur delusions (which we
often hear about in the movies), and also delusions of persecution.
Hallucinations, as we see in slide seven are perceptions
that occur in the absence of stimuli. These hallucinations can be one of
several things. They can be visual hallucinations, auditory hallucinations
(which tend to be the most common), olfactory hallucinations, and even
Disorders of thought, on the other hand, can be a couple
of different types. They can be disorganized; that is, you really donít
have any organization to your thoughts, or they can be irrational. So those
are the positive symptoms. Well what are some negative symptoms?
Well negative symptoms, as we see in slide nine, usually
occur during nonpsychotic periods. Generally these involve the loss of
normal behaviors. Usually these symptoms include reduced speech, low
initiative, you donít wanta get out of the house, get out of bed, etc. You
can also have social withdrawal so you become a hermit (living in your
little house up on the hill), and of course, as we talked about a little bit
earlier, a diminished affect, where you basically have no reactivity to
The diagnosis for schizophrenia consists of a couple of
major things. First of all, as we see in slide 10, you must be continuously
ill for at least six months. In addition to that, you need to have at least
one psychotic phase where you have some kind of delusion, a hallucination or
disordered thought, incoherence, or other symptoms. There are many, many
other symptoms that we can look at. You need to look at the DSM-IV for more
detail for each of these other symptoms and to get more accurate information
regarding the diagnosis of schizophrenia.
There are also many subtypes of schizophrenia. Iíve
listed four here (page 11). They are based on the symptoms presented by the
individual. Often (and the ones you often hear about in the movies) are
types such as paranoid schizophrenia. Catatonic schizophrenia, on the other
hand, tends to be where you become a statue, while disorganized
schizophrenia is where you have no organizational things going on around
Well, now that we have a general overview of
schizophrenia, letís talk a little bit about some causes of schizophrenia.
There are three major hypotheses that we talk about in relation to causes of
schizophrenia. In each of these, there is support and some problems. So,
letís talk about these in general.
The first one, as we see in slide 14, are genetic
contributions to schizophrenia. It is very probable that schizophrenia is
genetic. However, it is probably not caused by one particular type of
gene. The way we know this is by looking at what we call the monozygotic
twin studies. Monozygotic twins are twins that have the same genetic
structure. So, when one twin becomes schizophrenic, if itís truly, purely
genetic, what should happen is that the other should always become genetic.
However, that does not always occur. In general, itís probably caused by a
combination of several genes, but we really arenít sure which ones they
are. However, schizophrenia has been identified with some particular genes
on chromosome 22 and chromosome 6. But more detail and more research will
have to be forthcoming before we really know where it does come from.
The second major hypothesis for schizophrenia and the
development of schizophrenia is shown in slide 15. This is what is called
the brain abnormality hypothesis. This has been identified by CT scans and
through cerebral blood flow studies. As we see here in the slide 15, some
patients with schizophrenia often have one or more of the following; they
have some reduction of blood flow to the left globus pallidus, they have
problems with blood flow and other things in the frontal lobes, the
medial/temporal lobe is thinner, and on and on. In essence, all of these
indicate a reduced number of neurons, especially in a couple of different
structures, such as the temporal and frontal lobes. What are some causes of
this brain damage? Well, as we can see in slide 16, birth trauma has been
correlated with schizophrenia. In addition, viral infections that often
occur during the second and third trimester have also been correlated with
schizophrenia. Nutritional issues and other things as well have also been
correlated as well.
Well, as we can see in slide 17, schizophrenia is not
truly or purely a genetic problem. Itís not purely an abnormality problem
either. In essence, itís probably a combination of both and is triggered by
some kind of environmental event (such as influenza in the prenatal
period). However, regardless of all of the research that was going on right
now, weíre not really sure what causes the disorder, or why some individuals
become schizophrenic and others do not.
Well weíve talked now about two different hypotheses. The
third hypotheses that I want to cover begins on slide 18. This is one that
you probably have heard of and is called the dopamine hypothesis. The
dopamine hypothesis basically contends that you get positive symptoms (that
is, the psychotic symptoms) due to increased levels of dopamine. That is,
you get increased stimulation from dopanergic synapses. Whatís a little bit
of history about this particular model. Well, as we can see in slide 19,
Lorobit was looking for a drug to calm patients after neurosurgery that he
was doing. He was a neurosurgeon and what he found was that Chlorpromazine
worked very well. He hypothesized that if other patients use it they might
be calmed as well. Well, Delay and Deniker found that if you gave high
dosages of Chlorpromazine to people with schizophrenic or manic depressive
symptoms, it helped calm them down. This became the first major idea or the
concept behind the increased amount of dopamine causing schizophrenia.
Well, letís talk about some of these drugs a little bit.
The first of these drugs are called chlorpromazine and
what we call the classic phenothiazines, and part of this group is what we
call the typical antipsychotics. There are other ones that are listed there
In essence, chlorpromazine and the phenothiazines in
general have clear, clear effects on schizophrenia. They block the
hallucinations, they block the delusions, and they block the disoriented
thinking. As a result, the person tends to become more normal. There are
other drugs as well and some of these are basically shown on slide 21 and
these are what are called the atypical antipsychotics. These work for
negative symptoms and cognitive problems. They also have fewer side effects
than the traditional phenothiazines. Iíve listed three of them here and
weíll talk a little bit more about these later.
In essence, atypical antipsychotics bind to dopamine three
and dopamine four receptors, (which are primarily in the limbic system and
the cortex). We have very few of these, on the other hand in the basal
ganglia. As a result these cause what we call very few extrapyramidal side
effects; which includes things such as tardive dyskinesia which weíll talk
about a little bit later.
Well, what is some support for the dopamine hypothesis?
Well the first major set of support comes from drug studies. What we find
(as we see in slide 23) is when we give drugs that increase dopamine levels
to a high degree, such as with amphetamines or cocaine, we often produce
positive symptoms of schizophrenia. In addition, if we give drugs that
block dopamine receptors, we can reverse the symptoms of schizophrenia.
So, which of these receptors are important? Well, as we
can see in slide 24, thereís a wide variety of receptors, but all these are
related to the dopamine class. There are five different groups or five
different types of receptors in the dopamine category, D1 through D5.
Basically, D1 and D5 increase cyclic AMP (CAMP), theyíre in the hippocampus,
the cortex and the caudate nucleus. The D2 group, which includes D2, D3,
and D4 decrease CAMP. So, D1 and D5, are similar to GS proteins while D2
tend to be more like GI proteins. Ss we can see here, the D2 group is
located in different areas from the D1 group.
Well, what are some of the major systems that we examine
for dopamine. Well as we can see here on slide 25, there are four
tuberoinfundibular, Nigrostriatal, Mesolimbic, and Mesocortical. What about
the nigrostriatal system. Well as we see in slide 26, the nigrostriatal
system contributes to Parkinsonís disorders and may be involved with short
term and long term antipsychotic side effects. So, what we have are short
term problems such as hand tremors or muscle rigidity. Whereas, with
long-term problems and side effects, we have what we call tardive dyskinesia.
Tardive Dyskinesia is basically a set of symptoms where the person develops
significant muscle rigidity especially in the face. It often looks like a
person has a stone, drawn back face, and itís primarily due to the amount of
dopamine that we have in the system.
The mesolimbic system, as we see in slide 27, has several
structures as well and is primarily involved with emotion and memory. Here,
basically the symptoms of thought and perceptions are classic. You also see
epileptic seizures as well. Carson contends these positive symptoms result
from over-activity of the system.
Mesocortical areas begin in the ventral tegmental area and
projects onto the cortex. This set of structures is involved with things
such as motivation and planning, social behavior and other things. This
system is hypothesized to be involved with the negative symptoms of
schizophrenia. So what we see here is based upon the particular systems
that we are activating. What we end up having are different symptoms. This
model was put together and developed in more detail by Wineberger. As we
see in slide 29, Wineberger contends that there are two dopamine systems
impacted by schizophrenia. We get increased mesolimbic pathway activation
through the D2 group, especially D4, and these are associated with the
positive symptoms. Furthermore, we get decreased activity in the
mesocortical structures in the pre-frontal cortex and become associated with
negative symptoms. How does this occur? Well the mesocortical pathway
basically inhibits the mesolimbic pathway. So, as we see here, the
primarily effects of schizophrenia are reductions of inhibition.
Ultimately, when you get disinhibition in the mesolimbic pathway, you begin
to develop symptoms.
Well, what about some drugs used to treat schizophrenia.
As we can see in slide 31, there are many, many types. The drugs that are
given are based upon the symptoms and the potency needed. These drugs can
be typical antipsychotics or atypical depending on the symptoms. Iíve
listed here on slide 32 some particular drug names; chlorpromazine having
the highest potency and Spiperone having the lowest potency, but many, many
others are available as well.
The problem with many drugs in treatment of schizophrenia
and the delivery of drugs is what we call the side effects. Some of these
side effects are very, very pronounced. Some of these symptoms are shown in
slide 33. Some side effects include dry mouth, skin eye pigmentation, and
even breast development. The key one when we talk about a reduction of
dopamine due to antipsychotic medications, it called tardive dyskinesia.
We talked about being stone faced a little bit before, but you also get
facial ticks, gestures, etc. The main thing and main problem when we talk
about the side effects of schizophrenia are some of the other symptoms. In
essence, the person doesnít feel normal. When you donít feel normal (as you
do sometimes when you take particular medications), you donít feel right,
etc., what do you often do? (Answer) You stop taking your medications, and
when you stop taking your medications, the symptoms return.
So in conclusion, as we see in slide 34, schizophrenia is
a very severe disorder. However, most people (up to 80 to 90%) can be
treated very effectively if they take medications and take them regularly.
However, as we talked about before, many people (because of the side
effects) stop taking the medication. As a result, what we begin to develop
a revolving door symptom. The person goes into a hospital, they get put on
medications, they get stabilized, they leave the hospital, they go out on
the street, and for some reason stop taking their medication. Then they do
some sort of activity, the police arrest them, they go back to the
institution, and the process starts all over again.
The major work right now with schizophrenia and drugs used
to treat schizophrenia is decreasing the drug side effects and looking at
the genetics that are associated with the disorder. If you can develop
particular drugs, and you understand whatís going on in the receptor sites
and the brain structures, or if you understand the genetics behind the
disorder, you can make something to stop the disorder. As a result, if you
have minimal or no side effects, you will become very, very rich, plus win a
Nobel Prize and other things.
So in general, schizophrenia is very, very important. It
causes a lot of problems for people in the United States, and as a result,
costs a lot of money. Thus, there is major, major research going on to work
with this disorder.
In the next section we talk about another major set of
disorders and these are called the mood disorders and until then, we hope
youíre having a good day.