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  University of Idaho
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  Psychology Dept.
  University of Idaho
  Design - P&D

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 that’s 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, it’s 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 we’ll 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 emotion.

So, let’s 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 tactile hallucinations. 

Disorders of thought, on the other hand, can be a couple of different types.  They can be disorganized; that is, you really don’t 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 don’t 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 anything.

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.  I’ve 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 you.

Well, now that we have a general overview of schizophrenia, let’s 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, let’s 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 it’s truly, purely genetic, what should happen is that the other should always become genetic.  However, that does not always occur.  In general, it’s probably caused by a combination of several genes, but we really aren’t 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.  It’s not purely an abnormality problem either.  In essence, it’s 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, we’re not really sure what causes the disorder, or why some individuals become schizophrenic and others do not. 

Well we’ve 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.  What’s 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, let’s 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 as well. 

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.  I’ve listed three of them here and we’ll 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 we’ll 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, there’s 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), they’re 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 Parkinson’s 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 it’s 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.  I’ve 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 doesn’t feel normal.  When you don’t feel normal (as you do sometimes when you take particular medications), you don’t 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 what’s 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 you’re having a good day.