Part 3: Biological / Medical Models

Models of schizophrenia: Biological/MedicalMost likely questions are on the models or explanations of the causes of the psychotic disorder.  At A2 you will be expected to describe or outline the various theories and then either evaluate them or compare them to other approaches, such as psychological.

Genetic: Twin Studies, Family Studies, Adoption Studies

Dopamine Hypothesis

Brain Dysfunction: Enlarged ventricles and abnormal brain structure

The incidence of schizophrenia in the general population is 1%.  If the incidence within families is higher than this then it suggests a genetic link.  This section of the topic shows considerable overlap with earlier work on intelligence with the main body of evidence coming from twin studies, family studies and adoption studies.  As with intelligence it is vital to bear in mind that it is very difficult to separate out the effects of inheritance and environment (nature and nurture), even when monozygotic twins are reared apart.

Twin studiesGottesman & Shields (1972) examined the records of 57 schizophrenics between 1948 and 1964.   About 40% of the twins were determined to be MZ and about 60% DZ.  If the pair were discordant, that is one had schizophrenia and the other did not then the non- schizophrenic was followed for at least 13 years to see if it developed later.

Concordance rates, (i.e. probability of a twin having schizophrenia if its twin has the disorder) were as follows:

Monozygotic twins 42% Dizygotic twins 9%

Gottesman (1991) in a review of over 40 other studies found Monozygotic twins 48% concordance Dizygotic twins 17%

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Exam Questions: Discuss biological explanations of schizophrenia (25)

Outline and evaluate one or more biological explanations for schizophrenia. In your evaluation you should refer to research evidence. (25 marks)The focus in these questions is on biological explanations. AO1 = 9 marks Outline of one or more biological explanationsAO2 = 12 marks Evaluation of biological explanation(s)AO3 = 4 marks Methodological evaluation of studies/evidence cited as evaluation.Evaluate the explanation(s) of schizophrenia in terms of their strengths and weaknesses, effectiveness, including comparison with alternative explanations and the extent to which the explanations are supported by evidence.

Part 3: Biological / Medical Models

Heston (1970) found that if one MZ twin has schizophrenia that there’s a 90% probability that the other will have ‘some sort’ of mental disorder!

EvaluationWhat this suggests:

there is a genetic link for schizophrenia schizophrenia is not entirely genetic, otherwise the concordance for MZ twins would be 100% However, as with all studies of this sort it is vital to consider the role of environmental

factors.  MZ twins are more likely to be brought up in similar conditions, be treated similarly, same class at school, have similar friends and experiences, even be dressed and treated similarly.  Therefore it is not surprising that the concordance is so high. 

The usual way around this problem is to consider MZ twins reared apart.  However, as Gottesman (1991) discovered the concordance rates are similarly high.  But, the same proviso still applies.  Twins that are adopted into different families still tend to be reared similarly and are often adopted into members of the same family!  (Kamin 1977).

One other evaluation point is that until the advent of sophisticated genetic testing, it was very difficult to distinguish MZ and DZ twins, especially at birth.  Some of the statistics for MZ twins may actually be DZ twins and vice versa.      

One other point is that we tend to assume that MZ twins are treated more alike because they are MZ twins.  Lytton (1977) turned this on its head and suggested that the greater similarity of MZ twins ensures that they elicit a more similar response from their parents.  That is, the greater similarity of identical twins is a cause of their more similar parenting rather than an effect of it! 

 Family studies:Look at patterns of the disorder within families.  First degree relatives share an average of 50% of their genes, and second degree relatives share approx 25%. To investigate genetic transmission of schizophrenia, studies compare rates of schizophrenia in relatives of diagnosed cases compared to relatives of controls. Evidence suggests that the closer the biological relationship, the greater the risk of developing schizophrenia. Kendler (1985) has shown that first-degree relatives of those with schizophrenia are 18 times more at risk than the general population. Gottesman (1991) has found that schizophrenia is more common in the biological relatives of a schizophrenic, and that the closer the degree of genetic relatedness, the greater the risk.

Gottesman (1991) in a review of other studies published the following findings:Circumstances Probability of developing schizophrenia‘Randomly’ chosen from population 1%Brother or sister has schizophrenia 8%One parent has schizophrenia 16%Both parents have schizophrenia 46%

Perhaps the most powerful of all evidence for a genetic link is the following:

Gottesman & Bertelsen (1989).  If your parent is an identical twin who has schizophrenia then you have a 17% chance of getting it too, (compare with one parent in table).  However, if your parent does not have the disorder, but their identical twin does, then your chance of getting the disorder is still 17%.  This is good evidence because it seems to minimise environmental causes since you are not living with a schizophrenic.  However, you are living with someone who is predisposed to schizophrenia, (i.e. carries the genes for it), since they have the same genetic code as their twin who has developed it.

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Part 3: Biological / Medical Models

                        Dad (Richard)              Uncle Robert (Richard’s MZ twin)            Ryan

If Richard has schizophrenia then Ryan has a 17% chance of getting it too.  But this could obviously be due to environment rather than genetics since Ryan is living with his father.   However, supposing dad (Richard) has an identical twin (Robert) who is genetically identical.  Imagine a situation where uncle Robert is diagnosed with the disorder, so obviously has the genetic predisposition, but his brother Richard, (Ryan's dad) doesn't.   Richard must also have the genetic predisposition (he shares his genes with Robert) but shows no outward signs of this.  In such cases, the son still has a 17% chance of developing schizophrenia. 

This is very powerful evidence for a genetic cause since it shows that Richard (the father) who must be genetically predisposed to schizophrenia but has never shown the symptoms, has passed on the genes for it to his son, who has developed the disorder but without having been exposed to the behaviour.

Remember: in studies where twins have been separated at birth there is still one environment that they have shared for nine months; the womb. This may seem obvious and to some extent irrelevant but this is a vital time for the child’s development and pre-natal factors may be crucial in determining later functions.

Adoption StudiesA more effective way of separating out the effects of

environmental and genetic factors is to look at adopted children who later develop schizophrenia and care them with their biological and adoptive parents. The Finnish Adoption Study, which Tienari began in 1969 identified adopted offspring of biological mothers who had been diagnosed with schizophrenia (112 index cases), plus a matched control group of 135 adopted offspring of mothers who had not been diagnosed with any mental disorder. Adoptees ranged from 5-7 years at the start of the study and all had begun separation from their mother before the age of 4. The study reported that 7% of the index adoptees developed schizophrenia, compared to 1.5% of the controls.

A Danish Adoption Study, reported by Kety et al (1994), taking a national sample from across Denmark, found high rates of diagnosis for chronic schizophrenia in adoptees whose biological parents had the same diagnosis, even though they had been adopted by ‘healthy’ parents. The data provided by these prospective studies have indicated a strong genetic link for schizophrenia.

Findings Their biological parents, whose genes they possess, were more likely to have schizophrenia than the parents who had adopted them and brought them up.  

ConclusionGenes appear to play a role in schizophrenia although other factors must also be involved.  The chromosome or specific gene(s) responsible have not yet been identified. 

Heston (1947) studied 47 children born to schizophrenic mothers but who were separated from them within the first three days of life.  They were adopted into families not related to the biological mothers.  Later in life (30s) they were compared with a control group of children who had been separated in similar circumstances at birth, but crucially, not born to schizophrenic mothers.  Five of the 47 in the experimental group had gone on to develop schizophrenia (over 10%), whereas none of those in the control group had developed the disorder.

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Part 3: Biological / Medical Models

 

EvaluationsOne strength of the genetic explanation of schizophrenia is that there is strong empirical support provided by Kety et al. (1975). In one of the largest adoption studies, Kety used two groups of adoptess who were identified as: (a) 33 who had schizophrenia, and (b) a matched group who did not. Rates of the disorder were compared in the biological and adoptive families of the two groups of adoptees – the rate was greater among biological relatives of the schizophrenic adoptees than among those of the controls, a finding which supports the genetic explanation. Further, the rate of schizophrenia was not increased among couples who adopted the schizophrenic adoptees, suggesting that environmental factors were not of crucial importance. This suggests that there is wider academic credibility for the notion that genetics play an influential role in the development of schizophrenia.

One weakness of the genetic explanation of schizophrenia is that there are methodological problems. Family, twin and adoption studies must be considered cautiously because they are retrospective, and diagnosis may be biased by knowledge that other family members who may have been diagnosed. This suggests that there may be problems of demand characteristics.

A second weakness is the problem of nature-v-Nurture. It is very difficult to separate out the influence of nature-v-nurture. The fact that the concordance rates are not 100% means that schizophrenia cannot wholly be explained by genes and it could be that the individual has a pre-disposition to schizophrenia and simply makes the individual more at risk of developing the disorder. This suggests that the biological account cannot give a full explanation of the disorder.

A final weakness of the genetic explanation of schizophrenia is that it is biologically reductionist. The Genome Project has increased understanding of the complexity of the gene. Given that a much lower number of genes exist than anticipated, it is now recognised that genes have multiple functions and that many genes behaviour. Schizophrenia is a multi-factorial trait as it is the result of multiple genes and environmental factors. This suggests that the research into gene mapping is oversimplistic as schizophrenia is not due to a single gene.

Another weakness of the family studies is that they lack population validity. The reason for this is because the samples that are used are small in numbers and only a select number of families are used. This suggests that there are issues with the findings being generalised to the whole population.

Biochemical:  (Is there a chemical cause for schizophrenia?)

Dopamine hypothesisDopamine is a neurotransmitter. It is one of the chemicals in the brain which causes neurons to fire. The original dopamine hypothesis stated that schizophrenics suffered from an excessive amount of dopamine. This causes the neurons that use dopamine to fire too often and transmit too many messages. This message ‘over load’ may produce many of the symptoms of schizophrenia. Evidence for this comes from the fact that amphetamines increase the amounts of dopamine. Large doses of amphetamines given to people with no history of psychological disorders produce behaviour which is very similar to paranoid schizophrenia. Small doses given to people already suffering from schizophrenia tend to worsen their symptoms. Further evidence points to the connection between dopamine and schizophrenia comes from antipsychotic drugs to treat the disorder. They work by blocking dopamine receptors, so preventing dopamine-receiving neurons from firing. In addition, L-Dopa, which is used to treat Parkinson’s disease (caused by a lack of dopamine), can produce schizophrenic symptoms in individuals with no history of the disorder (Grilly, 2002).

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Part 3: Biological / Medical Models

A second explanation developed, which suggests that it is not excessive dopamine but the fact that there are more dopamine receptors. More receptors lead to more firing and an over production of messages. Autopsies have found that there are generally a large number of dopamine receptors (Owen et al., 1987) and there was an increase in the amount of dopamine in the left amygdale and increased dopamine in the caudate nucleus and putamen (middle of the brain).

Hallucinogenic drugs are chemically similar to the neurotransmitter dopamine.  Researchers therefore believed dopamine could be the cause.  They concluded that the brains of schizophrenics were more sensitive to dopamine than the brains of non-schizophrenics. 

Evidence for the dopamine hypothesis

 Amphetamines and cocaine increase the effects of dopamine in the brain.L-Dopa (a chemical that increases the levels of dopamine) can produce schizophrenic symptoms.Chlorpromazine, (an anti-psychotic drug frequently used in the treatment of schizophrenia), blocks dopamine receptor sites.  This makes the brain less sensitive to dopamine.  (See the diagram).

Post mortems carried out on schizophrenics, show that they have up to six times the number of dopamine receptors than normal.  Again this suggests that their brains are more sensitive than usual to the neurotransmitter.

However Chlorpromazine only reduces the positive symptoms of schizophrenia such as hallucinations

and delusions. Neuroleptic drugs (such as chlorpromazine) have their effect on the brain almost immediately,

but they take weeks to affect the behaviour of the patients.  The dopamine hypothesis is unable to explain this delay.

Chlorpromazine makes little or no difference to 30% of schizophrenics. The role of serotoninRecently, Kane (1988) said the drug clozapine has been used in the treatment of the disorder.  Clozapine is more effective in reducing the negative symptoms of schizophrenia (e.g. disturbances of speech and flattening of affect).  Clozapine seems to work by blocking serotonin sites in the brain.

ConclusionBoth dopamine and serotonin are probably involved, but the precise role played by each is unclear.

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Part 3: Biological / Medical Models

EvaluationAll the evidence provided is correlational.  It implies an association between schizophrenia and chemicals in the brain.  It does not prove cause and effect.  It could be that schizophrenia has caused the abnormal chemical levels rather than the other way around.

Strength of the research into schizophrenia is that it has practical applications. From the research using schizophrenics new drugs have been developed such as Clozapine, which is much more effective than neuroleptics at relieving schizophrenic behaviour. This suggests that Psychiatrists and GP’s can understand the role played by different drugs when treating different types of schizophrenia and thus improve the patients quality of life.

One criticism of the dopamine hypothesis is there is a problem with aetiology (cause). Is the raised dopamine levels the cause of the schizophrenia, or is it the raised dopamine level the result of schizophrenia? It is not clear which comes first. This suggests that one needs to be careful when establishing cause and effect relationships in schizophrenic patients.

A third criticism is that there is contradictory evidence for the biochemical explanation from Kasper et al. (1999). He suggests there are a number of problems with the dopamine hypothesis. First, antipsychotic drugs are effective for only positive symptoms. Therefore, excessive dopamine can at best explain only some types of schizophrenia. Second, newer atypical antipsychotic drugs (e.g., clozapine) have proved more effective than traditional ones in successfully treating the symptoms of schizophrenia despite blocking fewer dopamine receptors. This suggests that there is a problem with evidence for the notion of dopamine being the main contributing factor associated with schizophrenia.

A final weakness of the dopamine hypothesis is that it is biologically deterministic. The reason for this is because if the individual does have excessive amounts of dopamine then does it really mean that they will develop schizophrenia? This suggests that the dopamine hypothesis is not fully accounted for.

Neuroanatomical Explanations

Brain Dysfunctions - Enlarged Ventricles 1. Using PET, MRI and Cat scans researchers have discovered that many schizophrenics have enlarged ventricles, cavities in the brain that supply nutrients and remove waste. The ventricles of a person with schizophrenia are on average about 15% bigger than normal (Torrey, 2002).

Brown et al. (1986) found decreased brain weight and enlarged ventricles, which are the cavities in the brain that hold cerebrospinal fluid. Buchsbaum (1990)

found abnormalities in the frontal and pre-frontal cortex, the basil ganglia, the hippocampus and the amygdala. As more MRI studies are being undertaken, more abnormalities are being identified. Structural abnormalities have been found more often in those with negative/chronic symptoms, rather than positive/acute symptoms, lending support to the belief that there are two types of schizophrenia: Type 1 (acute) and Type 2 (chronic).

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Part 3: Biological / Medical Models

EvaluationA strength is that the research into enlarged ventricles and neurotransmitter levels have high reliability. The reason for this is because the research is carried out in highly controlled environments, with specialist, high tech equipment such as MRI and PET scans. These machines take accurate readings of brain regions such as the frontal and pre-frontal cortex, the basil ganglia, the hippocampus and the amygdala. This suggests that if this research was tested and re-tested the same results would be achieved.

Supporting evidence for the brain structure explanation comes from further empirical support from Suddath et al. (1990). He used MRI (magnetic resonance imaging) to obtain pictures of the brain structure of MZ twins in which one twin was schizophrenic. The schizophrenic twin generally had more enlarged ventricles and a reduced anterior hypothalamus. The differences were so large the schizophrenic twins could be easily identified from the brain images in 12 out of 15 pairs. This suggests that there is wider academic credibility for enlarged ventricles determining the likelihood of schizophrenia developing.

One weakness of the neuroanatomical explanation is the problem of cause and affect. Causation cannot be inferred as associations have only been identified. The brain dysfunction may be a symptom of the disorder rather than the cause, as the plasticity (flexibility) of the brain means that it may change as a result of abnormality. This suggests that there is a problem with the issue of aetiology, was it brain dysfunction that caused schizophrenia. Or was it schizophrenia which lead to brain dysfunction.

A second weakness of the neuroanatomical explanations is that it is biologically deterministic. The reason for this is because if the individual does have large ventricles then does it really means that they will develop schizophrenia? This suggests that the enlarged ventricles do not necessarily account for the abnormality.

Brain Dysfunctions: Neuro-developmental - Abnormal Brain Structure 2. Johnson (1989) reported that some schizophrenics have a reduced blink reflex (an involuntary blinking of the eyelids), evidence for neurological damage.  Others have reported that some schizophrenics have difficult births which could have starved their brains of oxygen.  This would also explain why the incidence of schizophrenia is declining as monitoring techniques at birth improve. 

Chua & Mckenna (1995) reported the following abnormalities in the brains of some schizophrenics:·         Smaller corpus collosum·         Less grey matter in the temporal lobes·         Enlarged ventricles resulting in loss of brain tissue (as above)·         Reduced activity in the prefrontal cortex

Evaluation However, none of these findings are consistent amongst schizophrenics.  The most common abnormality amongst patients is the enlarged ventricles which would result in less brain tissue, particularly in the medial temporal lobes of the brain.  This has been confirmed using techniques such

as MRI scans. 

It could be argued that this does not show cause and effect.  Perhaps the schizophrenia led to the abnormal brain structure.  However, Harrison (1995) believes that these differences occur before the onset of schizophrenia, implying that they are more likely to be a cause than an outcome of the

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Part 3: Biological / Medical Models

disorder.  Since the abnormalities in brain structure do not increase over time, as is the case with diseases like Alzheimer’s, then it appears that the problems are due to a failure of the brain to develop normally in the first place.       

Evaluation One criticism often aimed at the possible relationship between brain damage and

schizophrenia is that no one pattern of damage seems to correlate with the disorder.  Perhaps, however this should not be surprising, given the variety of symptoms associated with schizophrenia.  It seems that certain damage is associated with certain symptoms.  Damage to the temporal lobe is associated with some of the positive symptoms whereas damage to the frontal lobe is associated more with the negative symptoms.

Any such differences between the brain of a ‘schizophrenic’ and ‘non-schizophrenic’ brain are so small that it is not possible to detect them in the individual.  They only become apparent if groups of schizophrenics and non-schizophrenics are compared.

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Diathesis-stressNo essay on the causes of schizophrenia would be complete without a mention of this.  It is particularly good since it can be used in either a question asking for medical explanations or one seeking information on the social and psychological explanations.

Diathesis is a person’s genetic predisposition to a particular disorder.  Because of the genes they've inherited some people are more likely to develop schizophrenia than others.  However, this alone does not guarantee that they will.  (Think of MZ twins, one of whom has the disorder and the other who does not).

Stress refers to the environmental factors that trigger it, for example high levels of expressed emotion, major life events or a dysfunctional family.

SupportTienari (1987) found that in all cases of schizophrenia that he studied one or other members of the sufferer's family were disturbed. Marcus (1987) Israeli study, all parents of schizophrenics studied had poor parenting skills.

SzaszSzasz is a powerful critic of the psychiatric model (biological).  Psychiatrists see ‘mental disorders’ as being of physical origin.  To Szasz this is contradictory.  If illness has an organic (or physical cause) then it should be classed as a disorder of the brain.  Although there are various biological models of disorders, such as schizophrenia, as yet none are proven.  As Szasz points out, in the majority of cases of patients with ‘mental illness’ there is no obvious physical defect in brain structure or genetic make- up.  (Exceptions are Alzheimers, Korsakoffs etc.). To Szasz, ‘mental illness’ is ‘a problem of living’ brought on by the bizarre nature and structure of societies.  As such they should be seen in an ethical and social context and not simply treated by the administration of drugs. Other comments on schizophreniaValidity of the disorderIs schizophrenia one disorder or a number of related disorders? There is evidence for the latter:

Many of the symptoms occur in other mental disorders, e.g. thought disorder in maniahallucinations in some forms of depression

The onset of the disorder can be sudden or insidious (person being unaware of the early stages).

Its course can be continuous (no breaks), or episodic.

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Part 3: Biological / Medical Models

Prognosis (outcome of the disorder): 50% go on to develop moderate or severe symptoms, 25% make a full recovery.

In contrast, the psychological explanation rejects the view that schizophrenia is caused by genetics and brain chemistry. Instead it favours the idea that the disorder is caused by life events - the environment, upbringing family etc. For example, research shows that dysfunctional family interaction, where there is a lot of “expressed emotion”, can lead to schizophrenia. This suggests that the biological account does not provide a full explanation of schizophrenia.

In conclusion the Diathesis Stress Model, which suggests that there is a genetic vulnerability to a disorder (Diathesis), but this is triggered when an individual has been exposed to a stressful life event. Both of these factors are necessary for a disorder to develop. This is why not all the children with schizophrenia develop the disorder, and why the concordance rate for mental disorders for MZ twins is nothing like 100%.

Exercise:

Schizophrenia and drug use-

1. Please make notes on the part played by the use of cannabis and development of schizophrenia, with evaluations (p 298).

2. Do mind maps of two biological explanations of schizophrenia

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