Specification: Biological explanations for schizophrenia: genetics and neural correlates, including the dopamine hypothesis.

Genetic Explanations of Schizophrenia

There are two main arguments when it comes to the genetic explanation of schizophrenia: sufferers have inherited a predisposition from their parents or that specific genes cause the illness.

Inheritance

There is considerable evidence, which indicates that schizophrenia runs in families and is in part, genetic. Evidence in favour of a genetic link, comes from family studies which indicate that the closer the genetic relationship to someone with schizophrenia, the greater the chance of developing the disorder. Gottesman (1978) reports that while the rate of schizophrenia in the general population is 1%, the chances of first degree relatives (for example parent and child or sibling) developing the disorder is 12%, furthermore if both parents have schizophrenia, there is a 40% likelihood that a child of theirs will develop the disorder. Overall, Tsuang et al (1990) estimated that a first-degree relative of a schizophrenic has a 5-20 times higher risk of developing the illness. 

Further evidence comes from twin studies. In general, it is reasonable to assume that if Monozygotic (MZ) twins have a higher concordance rate than Dizygotic (DZ) twins, then this indicates a degree of heritability. Both types of twin share the same environment, but only the MZ twins have identical genetic make-up. Research has found much higher concordance rate in MZ twins in comparison to DZ twins. For example, Gottesman and Shields (1972) found a concordance rate of 42% for MZ and 9% for DZ. In addition, a study in London using the Maudley Twin Register by Cardno et al. (1999) found a 40% concordance rate in MZ twins, compared to 5.3% in DZ twins. This research shows that individuals with identical genetic makeup (MZ twins) have an increased risk of developing schizophrenia in comparison to DZ twins, who only share half of their genes. 

However, one of the problems with any comparison of concordance rates between people in the same family, is that they also share a similar environment. A more effective way of isolating the effects of environmental and genetic factors is to look at levels of schizophrenia in adopted children and compare them with their biological and adoptive parents, using adoption studies. Heston (1966) compared 47 children of schizophrenic mothers who had been fostered or adopted during the first month of their life with a control group of 50 children who had been raised in the same homes as these children. None of the control group developed schizophrenia but 17% of the children with schizophrenic biological mothers did. Furthermore, these 47 children were far more likely to have been diagnosed with other psychological abnormalities, and to be involved in criminal activities than the control group. This study shows that having a schizophrenic mother i.e. having some of her genetic material, increased a child’s chances of having schizophrenia and other mental illnesses, even when not being raised by her or sharing the same environment. 

Specific genes

Due to a number of genes being implicated in schizophrenia, it looks like schizophrenia is polygenic (i.e. it requires a number of factors to work in combination). To make things more complicated, because different studies have identified different candidate genes, it also appears schizophrenia is aetiologically heterogeneous (i.e. schizophrenia may be caused by many different genes). For example, Miyakawa et al. (2003) studied DNA from families affected by schizophrenia, and found that those with the disease were more likely to have a defective version of a gene, called PPP3CC. This gene is associated with the production of calcineurin, which regulates the immune system. But Sherrington et al. (1988) found a gene located on chromosome 5, which has been linked in a small number of extended families with the disorder. Research appears to be implicating different genes; it is not clear whether it is one single gene or several working together which causes the illness. 

Evaluation of genetic explanations

There is little doubt that genetic factors influence the risk of developing schizophrenia. However, it cannot be the sole factor since the concordance rates for MZ twins, who are genetically identical, are between 40-60%. As the concordance rates are not 100% it means that genes cannot wholly explain schizophrenia. It could be that an individual is pre-disposition to schizophrenia, making them more at risk. The evidence certainly suggests that the genetic account cannot give a full explanation of the disorder. By focusing on one factor i.e. genes it has adopted a biologically reductionist approach and not considered any other factors biological or otherwise, such as biochemistry or family dynamics. Using this very narrow approach has led to an explanation which cannot explain why if one MZ twin has schizophrenia why the other twin only has a 40-60% risk of getting it too. 

A problem with the genetic argument is that it is difficult to separate the impact of nature and nurture. For example, both family and twin studies investigate individuals who are sharing the same environment, which could be increasing the concordance rates, irrespective of the genes. Possibly the high concordance rates between MZ twins is actually due to them being treated more similarly than DZ twins or ordinary siblings and not in fact due to their genetics. Even MZ twins that are reared apart share the same womb environment before birth. The shared environment could be a confounding variable as we can’t differentiate between genetic and environmental influences. 

Family studies are conducted retrospectively when they are comparing a cross section of people who have already been diagnosed. Retrospective data can be unreliable as problems in memory and records are likely. Prospective studies provide more reliable data as they follow people over time and can make comparisons before and after their condition occurs. 

It is important to note that two-thirds of people with schizophrenia have no relative with a similar diagnosis and therefore have no one to inherit it from. However, one explanation for this is a mutation in parental DNA, for example, in paternal sperm cells. This can be caused by radiation, poison or viral infection. Evidence for the role of mutation comes from a study (Malaspina et al. 2002) showing a positive correlation between paternal age (associated with increased risk of sperm mutation) and risk of schizophrenia, increasing from around 0.7% with fathers under 25 to over 2% in fathers over 50. 

Research into the location of specific genes has not produced definitive results. Making it impossible to understand the underlying mechanism that leads from the genetic risk to the disorder. 

It is more probable that both hyper- and hypodopaminergia are correct explanationshigh and low levels of dopamine in different regions are implicated in schizophrenia. 

Davis et al. (1991) updated the theory because high levels of dopamine are not found in all schizophrenics, and the modern anti-schizophrenic drug clozapine, with very little dopamine-blocking activity, works effectively against the illness. They suggested that high levels of dopamine in the mesolimbic dopamine system are associated with positive systems, while high levels in the mesocortical dopamine system are associated with negative symptoms (see table above). 

Evaluation of the dopamine hypothesis

A weakness of the hypothesis is that newer drugs such as clozapine, are more effective than traditional ones. These new drugs affect dopamine as well as other neurotransmitters, such as serotonin. It appears that several neurotransmitters may be involved in the development of schizophrenia and therefore the hypothesis is too simplistic. Along with dopamine and serotonin, some research has implicated glutamate. 

A strength of the research into the dopamine hypothesis is that it has practical applications as it has led to the development of an effective treatment. 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 can understand the role played by neurotransmitters when treating different types of schizophrenia and thus improve the patient’s quality of life. 

Research evidence shows that schizophrenia sufferers have more dopamine receptors. Having more receptors may lead to more neural firing and therefore an over production of messages. Autopsies have found that there are generally a larger number of dopamine receptors in schizophrenics (Owen et al. 1987) and an increased amount of dopamine in the left amygdala (Falkai et al. 1988) and increased dopamine in the caudate nucleus and putamen (Owen et al. 1978) in patients suffering from schizophrenia. These studies indicate that that there is evidence of dopamine abnormalities in the brains of schizophrenics. 

Dopamine abnormalities are not present in all schizophrenics, especially those with negative symptoms. Problems with dopamine seem to be associated more with positive symptoms, so it may only explain certain aspects or types of the illness. Davis et al. (1991) argue that the diversity of types and symptoms in schizophrenia implies that there are several neurotransmitters involved and not just dopamine. 

One criticism of the dopamine hypothesis is there is a problem with the chicken and egg i.e. cause and effect. Are the raised dopamine levels the cause of the schizophrenia, or are the raised dopamine levels the result of schizophrenia? It is not clear which comes first. Lloyd et al. believe that if dopamine is a causative factor, it may be in indirect one mediated through environmental factors, because abnormal family circumstances can lead to high levels of dopamine, which in turn triggers the schizophrenia symptoms. This suggests that one needs to be careful when establishing cause and effect relationships in schizophrenic patients. The differences in the biochemistry of schizophrenics could just as easily be an effect rather than a cause of the disorder. 

Neural correlates

This approach believes that schizophrenia has developed due to structural and functional brain abnormalities i.e. specific brain areas are associated with the disorders development. Originally evidence was limited to post-mortems conducted on the brains of dead schizophrenics, but research now uses non-invasive scanning techniques such as an fMRI, which gives a picture of the brain in action through the use of magnetic fields and radio waves. This means that the functioning of the brains of schizophrenics can be compared with that of non-sufferers, to identify brain areas that may be linked to schizophrenia. This is best achieved by giving tasks to participants associated with types of functioning known to be abnormal in schizophrenia, for example social cognition, thought processing and working memory tasks. 

This explanation proposes that schizophrenia is caused by enlarged ventricles. These are the fluid-filled gaps between brain areas. Enlarged ventricles are especially associated with damage to central brain areas and the prefrontal cortex. Such damage is often associated with negative symptoms. For example, Johnstone et al. (1976) found that schizophrenics had enlarged ventricles while non-sufferers did not, which suggests schizophrenia is related to a loss of brain tissue. 

Evaluation of neural correlates

Research indicates the enlarged ventricles may only explain certain schizophrenia symptoms. Weyandt (2006) reported that enlarged ventricles are associated with negative symptoms only. This implies that this explanation cannot explain all symptoms and types of the illness. 

Research into the role of enlarged ventricles is inconclusive. Some nonschizophrenics have enlarged ventricles, while not all schizophrenics do. This goes against the ideas of schizophrenia being linked to a loss of brain tissue. If it were the sole cause every person with enlarged ventricles would suffer from the illness. 

Evidence suggests that schizophrenics that do not respond to medication are those with enlarged ventricles. This could mean that it is an effect of suffering from schizophrenia over a long period of time i.e. it is the schizophrenia causing longterm physical brain damaged rather than the brain damage causing the schizophrenia. Therefore, the enlarged ventricles could be a consequence of the illness rather than the cause. 

Linked to the point above, there is research that does indicate that structural brain damage is often evident at first onset of schizophrenia. But only by performing longitudinal studies would it be possible to assess whether the damage progressively worsens as the schizophrenia continues. Ho et al. (2003) performed MRI scans on recent-onset schizophrenics and then re-scanned them 3 years later. They found evidence of brain damage in the recent-onset patients, which worsened over time (even though they were on medication). This suggests brain damage does increase in schizophrenics over time i.e. as the person’s schizophrenia continues their brain structure continues to change for the worse. 

Possible exam questions

1. Outline one biological explanation of schizophrenia. (4 marks)

2. Briefly evaluate the dopamine hypothesis as an explanation of schizophrenia. (6 marks)

3. Briefly evaluate neural correlates explanations of schizophrenia. (6 marks)

4. Jonte has been diagnosed with schizophrenia. His psychiatrist commented that two of his aunts have schizophrenia.
   Explain why the psychiatrist might have made this comment. (3 marks)

5. Describe and evaluate biological explanations for schizophrenia. Refer to both negative and positive symptoms in your answer. (16 marks)

6. Describe and evaluate at least one biological explanation of schizophrenia. Refer to empirical evidence in your answer. (16 marks)

7. There is considerable evidence that schizophrenia is caused by biological factors. Discuss biological explanations of schizophrenia. (16 marks)