Biological explanations of schizophrenia



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Biological explanations of schizophrenia

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Genetic explanation for schizophrenia

It has been known for a long time that schizophrenia runs in families. It could be because family members share the same disadvantaged environment, but a large body of research evidence suggests that genetic factors are also important. This evidence comes from:

Evidence from family studies

First-degree relatives (parents, siblings and offspring) share an average of …………. % of their genes, and second degree relatives share approx ………..%. To investigate genetic transmission of schizophrenia, studies compare rates of schizophrenia in relatives of diagnosed cases with relatives of controls. There is now a considerable body of evidence that suggests that the ………………………..the biological relationship, the ……………………………..the risk of developing schizophrenia or a related psychotic disorder. For example, Kendler et al (1985) have shown that first degree relatives of those with schizophrenia are 18 times more at risk than the general population.

AO3 of evidence

Family studies are often inconclusive because they are conducted retrospectively, that is, they are comparing a cross section of people who have already been diagnosed. A prospective (longitudinal) study can provide more reliable data because it follows the same group of people over a period of time and can make comparisons before and after any signs of illness occur. A number of large scale projects have been undertaken in different parts of the world

Evidence from twin studies AO2- Support

Twin studies offer another way of establishing genetic links by comparing the difference in concordance rates (i.e. the likelihood of both twins being affected with the disorder) for identical (MZ and fraternal (DZ) twins. Both share the same ……………………………………, but only the MZ twins have ……………………..genetic makeup. Many twin studies have been conducted and they all show a much …………………………………..concordance rate in MZ than in DZ twins.

To separate out genetics conclusively from the environment, researchers have sought out MZ twins reared ………………….where at least one twin has been diagnosed with schizophrenia. Obviously, they are few in number and an added problem is that one of the reasons for separation may have been a problem in the family.

Gottesman and Sgields (1982) used the Maudsley twin register and found 58% (7 out of 12 MZ twin pairs reared apart) were concordant for schizophrenia. If the genetic hypothesis is correct, then the offspring of a non-affected discordant MZ twin should be still high-risk. A study by Fischer (1971) found that 9.4% of such offspring developed schizophrenia, which is a much higher incidence than in the general population (approx 1%). A study in London using the Maudsley register by Cardno et al (1999) found a 40% concordance rate in MZ twins, compared with 5.3% in DZ twins. This evidence suggests that genetic factors are important.

Evaluation

Even in rare cases where MZ twins are reared apart, they still share the same environment in the womb before birth, so the contribution of environmental factors cannot be entirely discounted.

AO1- Evidence from adoption studies

A more effective way of separating out the effects of environmental and genetic factors is to look at adopted children who later develop schizophrenia and compare them with their biological and adoptive parents. The Finnish Adoption Study, which Tienari began in 1969, identified adopted-away offspring of biological mothers who had been diagnosed with schizophrenia (112 index cases), plus a matched control group of 135 adopted-away offspring of mothers who had not been diagnosed with any mental disorder. Adoptees ranged from five to seven years at the start of the study and all had been separated from their mother before the age of four. The study reported that 7% of the index adoptees developed schizophrenia compared with 1.5% of the controls (Tienari et al 1987).

The Danish Adoption study, reported by Kety et al (1994) taking a national sample from across Denmark, found high rates of diagnosis from chronic schizophrenia in adoptees whose biological parent had the same diagnosis, even though they had been adopted by ´healthy´ parents.

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The data provided by these prospective studies have, so far, indicated a strong genetic link for schizophrenia. However, data from adoption studies have to be analysed carefully. Tienariet al (2000) showed that the risk for developing schizophrenia was ……………. times greater in adopted children with biological mothers suffering form schizophrenia than in adopted children with biological mothers without schizophrenia.

Wahlberg et al (2000) re-examined the same data and found that there was a strong interaction between genetic and environmental factors. It seemed that only children who were adopted into families with poor communication were at risk of developing schizophrenia.

Another problem in these longitudinal studies is that diagnostic criteria for schizophrenia are continually being updated and changed.

AO2 of genetic explanation of schizophrenia

Twin, adoption and family studies continue to provide reliable evidence that the degree of risk increases with the degree of genetic relatedness.

Research evidence

There is now very strong evidence particularly from adoption studies, that genetics are a clear risk factor for schizophrenia. Although studies have shown clearly that the risk of schizophrenia is increased if close relatives have been diagnosed with the disorder, the chances are never 100%. Even if a MZ twin has the disorder, the risk of for the other twin is less than 50%.

This suggests ……………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………..Furthermore, about 89% of people with schizophrenia have no known relative who has been diagnosed with the disorder, so other factors are clearly responsible in these individuals.

Search for relevant genes

Research into the location of specific genes has not yet produced definitive results, although several have been implicated. Without knowing which precise genes are involved, it is impossible to understand the underlying mechanisms that lead from the genetic risk to the symptoms of the disorder. The search for specific genes continues.

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|AO1 |AO2 Genetic explanations |

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[pic]If genetic factors are important, they are likely to work by exerting an influence on the hardware of the brain. In other words, structural or biochemical abnormalities should be detectable in the brains of those diagnosed with schizophrenia. In particular, research interest has focused on the action of certain neurotransmitters (chemicals that act a schizophrenia messengers to transmit impulses from one nerve cell to another across the gap between adjacent nerve cells, called the synapse).

Studies of drugs like amphetamines and LSD, which are know to increase dopamine activity, have provided further support. These drugs can induce positive symptoms very similar to acute schizophrenia in healthy individuals and can exacerbate symptoms in people who are already vulnerable.

In a study by Randrup and Munkad (1966), behaviour similar to that found in those suffering form schizophrenia was induced in rats by administering amphetamines. The effects were then reversed by neuroleptic drugs.

AO2 of the dopamine hypothesis

Post mortem and PET scans further support for the dopamine hypothesis comes from post-mortems. These have revealed a specific increase of dopamine in the left amygdale (Falkai et al 1988) and increased dopamine receptor density in the caudate nucleus putamen (Owen et al 1978).

However, it is not clear whether these increases are a cause or a result of schizophrenia. Given the findings from post-mortems, and assuming that dopamine is the important factor in the action of antipsychotic drugs, then it would be expected that dopamine metabolism is abnormal in patients with schizophrenia. With the development of PET scans, metabolic activity can now be monitored in living brains.

PET scan research conducted by Wong et al (1986) revealed that dopamine receptor density in the caudate nuclei is indeed greater in those with schizophrenia (particularly those with positive symptoms) than in controls.

Problems of cause and effect

Unfortunately, neither post-mortems nor PET scans can reveal whether increases

dopamine activity causes schizophrenia or whether schizophrenia interferes with

dopamine metabolism.

Effectiveness of drug treatments.

Drugs alleviate positive symptoms, but are not so effective with negative symptoms. It is possible that the inconclusive findings in dopamine studies merely reflect two different forms of schizophrenia (Type I and Type II). Amphetamines (known to affect dopamine activity) worsen positive symptoms associated with acute schizophrenia and lessen negative symptoms associated with chronic schizophrenia, whilst phenothiazines (antipsychotic drugs) alleviate positive symptoms, but are not so effective at lessening negative symptoms. However, there are some people with schizophrenia who so not respond at all to neuroleptic drugs which suggests that a faulty dopamine system is not always a causal factor.

Role of other neurotransmitters-

One of the most effective drugs in treating schizophrenia is clozpine. This drug has its major effect on the serotonin system rather than the dopamine system, suggesting that other neurotransmitters could also be causal factors in schizophrenia.

Role of dopamine in other disorders

Dopamine is unlikely to be the only factor in schizophrenia because it has also been implicated in mania and a number of other mental disorders which have quite different symptoms. Each of these disorders is alleviated by quite different drugs, yet the main evidence for the dopamine link in schizophrenia is the main effectiveness of phenothiazines in alleviating symptoms

Reductionism

A criticism of biochemical explanations of schizophrenia is that they are reductionist i.e. they reduce a complex behaviour such as schizophrenia down to a relatively simple level of explanation i.e. an imbalance in brain chemicals. The influence of brain chemicals such as dopamine is indisputable but to argue that they can cause schizophrenia is to neglect all other potential influences (such as stress or irrational though processes) in the course of this disorder.

Given that no biological explanation accounts for all cases of schizophrenia or even for all aspects of the disorder within an individual, it seems likely that social and psychological factors play a part.

TIP

In the exam, do not fall into the trap of criticizing biological explanations because they fail to take into account environmental factors. Biologists accept that disorders like schizophrenia arise through an interaction between biological and environmental factors.

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|AO1 |AO2 Dopamine hypothesis |

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Summary questions

1. What is meant by the ´nature-nurture´debate in the context of schizophrenia?

……………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………Explain why twin, family and adoption studies are useful in investigating the causes of schizophrenia.

………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………How do researchers investigate genetic factors in the origins of schizophrenia?

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2. Briefly outline the Dopamine hypothesis

……………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………Explain why the effectiveness of clozapine has cast some doubt on the dopamine hypothesis.

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3. What are some of the problems of investigating biochemical and neuro anatomical factors.

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Biological treatments arise from the medical model of abnormality which considers mental disorder to be an illness or disease resulting from underlying biological factors. There are various biological treatments, such as drug therapy, electro-convulsive therapy (ECT) and psychosurgery. Most people with schizophrenia receive some form of medication (drug therapy). Drugs are administered in tablet form or sometimes by injection.

Early treatment for schizophrenia

One early form of treatment, first performed by Moniz (1936), was the prefrontal lobotomy, a form of psychosurgery in which sizeable portions of brain tissue were destroyed (Moniz, 1936).

There was no evidence that this drastic treatment was effective but plenty of evidence to show that it caused serious, even life threatening side effects and do was an inappropriate therapy. It was eventually abandoned as a therapy for schizophrenia in the 1950´s when antipsychotic drugs were discovered. With the introduction of more sophisticated equipment and techniques, psychosurgery is now a much more redefined process. However, it is only used as a last resort and rarely, if ever, in cases of schizophrenia.

(news.bbc.co.uk) 29 June 2002.

ECT is another controversial, early therapeutic technique, developed in the 1930´2. ECT was developed as a treatment for schizophrenia but it was found that it had a little effect on the disorder and has now been largely abandoned.

Drug therapy AO1

Drug therapy (chemotherapy) the most common treatment for schizophrenia, uses antipsychotic drugs. Some of these (called ´conventional/typical´) antipsychotic drugs are used to reduce the effects of dopamine, while others (called atypical antipsychotic drugs) also work on reducing serotonin activity.

Blocking Dopamine receptors

Biological researchers believe that dopamine plays an important part in the origins of schizophrenia. An important goal of antipsychotic drug therapy, then, is to reduce the amount of available dopamine or to reduce the number of dopamine receptor sites by blocking them. Phenothiazines (also known as neuroleptics) are a class of drugs which work by blocking dopamine receptors. One of the most frequently used is chlorpromazine. There is considerable evidence to suggest that these drugs can reduce the acute, positive symptoms (e.g. hallucinations) in many people with schizophrenia. They produce the maximum benefits within the first six months of use.

Blocking serotonin receptors

More recently, atypical anti-psychotic drugs such as clozapine have been introduced. These seem to take their effect by blocking serotonin rather than dopamine receptors. Research suggests that these drugs are more effective than the conventional antipsychotic drugs (Julien 2005)

Can you think of any advantages or disadvantages of the use of drug as a way to treat schizophrenia.

|Advantages |Disadvantages |

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Drug Therapy AO2

Effectiveness

Antipsychotic drugs-

The management of schizophrenia has been revolutionalised by the antipsychotic drugs, which can rapidly reduce the most disturbing symptoms and can decrease the amount of time spent in hospital. Both conventional and atypical antipsychotic drugs have been shown in many studies to be an effective form of treatment. They produce a sedative effect and can significantly reduce psychotic symptoms of hallucinations and delusions. This enables patients to live a relatively normal life in the community and has transformed schizophrenia from a hospital ´long-stay´to a hospital ´short-stay´condition. In fact many patients in Britain are now able to be treated on an outpatient basis.

The conventional drugs, though successful in reducing positive symptoms, have little effect, however, on negative symptoms (e.g. loss of motivation). Atypical drugs, on the other hand, also seem to improve negative symptoms (deLima et al 1005).

Relapse

It has been found that symptoms often return if patients stop taking the drugs (Rzewuska 2002) and patients sometimes have to be kept on maintenance doses for long periods of time. This increases the risk of serious side effects.

Appropriateness- Side effects

The conventional antipsychotic drugs produce some very serious side effects which raise doubts about their appropriateness as a treatment for schizophrenia . One is the development of symptoms similar to those found in Parkinson’s disease, such as stiffness, immobility and tremors. In its most serious from, it leads to a condition called ´tardive dyskinesia´, which includes uncontrollable sucking and smacking of the lips and facial tics. It is thought that this is caused by phenothiazines destroying parts of the brain. This occurs in around 30% of those taking the drugs and the risk increases with prolonged usage (Gualtieri, 1991). Other side effects include: low blood pressure, blurred vision and constipation.

The newer drugs are more effective and cause fewer side effects than conventional drugs. However, clozapine has a potentially life threatening side effect resulting in damage to the immune system. Other drugs then have to be administered to counteract this effect and regular blood tests are necessary. This makes treatment very expensive and limits its availability. The other typical drugs do not have this effect but they are also very expensive and can cause unwanted weight gain.

Compliance

Some patients refuse to comply with drug treatment regimes, possibly because of the side effects or sometimes because of poor memory. Research has indicated that if antipsychotic drugs are stopped abruptly, then symptoms recur (e.g. Davis et aal 1993). This has led to the ´revolving door syndrome of continual discharge into the community followed by readmission to hospital.

One way of avoiding this problem is to provide depot antipsychotic medication, which is given by injection into large muscle (usually the buttock) so as to lessen any discomfort and swelling. It is usually administered by a nurse in the patient’s home, in a doctor’s surgery or in an outpatient’s clinic. Depot injections release the medication slowly into the body over a number of weeks. The main advantage is that they only need to be given at intervals (once a week, or in some cases, once a month), which means that the patient does not have to remember to take several tablets a day.

Ethical issue

Some people have criticized whether the widespread use of drugs in the treatment of mental disorders is appropriate, referring to them as ´chemical straitjackets´. The argument is that the drugs are dehumanizing and take away any sense of personal responsibility or control. The ethical issue of informed consent is also a consideration. People in a psychotic state are not really in a position to give truly informed consent about their treatment.

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|AO1 Drug therapy |AO2 Drug therapy |

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Family studies

Twin Studies

Adoption studies

Specification: Section A

Psychopathology

• develop knowledge and understanding of schizophrenia

•Apply knowledge and understanding of models, classification and diagnosis to their chosen disorder.

• Clinical characteristics of the chosen disorder

• Issues surrounding the classification and diagnosis of their chosen disorder, including reliability and validity

• Biological explanations of their chosen disorder, for example, genetics, biochemistry

• Psychological explanations of their chosen disorder, for example, behavioural, cognitive, psychodynamic and socio-cultural

• Biological therapies for their chosen disorder, including their evaluation in terms of appropriateness and effectiveness

• Psychological therapies for their chosen disorder, for example,behavioural, psychodynamic and cognitive-behavioural, including their evaluation in terms of appropriateness and effectiveness

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Dopamine production

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It is thought that some of the symptoms of schizophrenia are a result either of an excess of dopamine in the brain or of a super-sensitivity of the dopamine receptors. In either case, schizophrenia is believed to occur as a result of over-activity in parts of the brain controlled by dopamine.

Interest in the neurotransmitter dopamine arose when it was found that neuroleptic, antipsychotic drugs, which work by inhibiting dopamine activity, can reduce the symptoms of schizophrenia. Conversely, L-dopa (a synthetic dopamine-releasing drug) can induce symptoms resembling acute schizophrenia in non-psychotic people.

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Blocking Dopamine receptors

Blocking Serotonin receptors

Effectiveness

Side effects

Compliance

Relapse

Ethical issues

Adoption studies

Family studies

AO1 Dopamaine hypothesis

AO1 Genetic explanations

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