A2 Option: Biological explanations for schizophrenia: genetics, the dopamine hypothesis and neural correlates.
The function of neurotransmitters as a theory/explanation and one other biological theory/explanation.
A2 Option: explanations of schizophrenia Genetic (e.g. Gottesman and Shields, 1972); biochemical (dopamine hypothesis)
The Dopamine Hypothesis
The dopamine hypothesis is a theory that argues a biological explanation of schizophrenia. It suggests that the unusual behaviour and experiences of schizophrenia can be explained by changes in dopamine function in the brain. Dopamine is one of many chemical neurotransmitters which send messages of neuronal synapses.
The hypothesis suggests that there are an excess number of dopamine receptors at the post-synaptic membrane (receiving end of the dopamine) of neurones in schizophrenic patients.
This is partly based on a number of studies that look at the effects of drugs on dopamine receptors and behaviour. It is also suggested that positive symptoms of schizophrenia might be due to an increase in dopamine in one part of the brain, and negative symptoms due to an increase in another part. Both PET scanning and animal studies have been used to look at excess dopamine receptors.
One suggestion is that development of receptors in one area of the brain might lead to the inhibition of their development in another area, so explaining why there are different numbers of dopamine receptors in different parts of the brain. There also seems to be links between damage to the prefrontal cortex and schizophrenia. This area finishes developing in adolescence which is when the onset of schizophrenia may be observed. Much support for the dopamine hypothesis comes from drugs studies, in particular those involving amphetamines (speed), which are dopamine agonists and so prevent the breakdown of dopamine, leading to high levels. When amphetamines are given in large quantities, they lead to delusions and hallucinations, similar to those in schizophrenic patients, and symptoms get even worse when given to patients of schizophrenia.
The table below shows pieces of evidence for and against the hypothesis.
Brain dopamine can only be measured only in the postmortem brain, and then only with some technical difficulties. Because of this, researchers have largely had to be content studying dopamine indirectly by measuring its major metabolite (what most of it is converted into). The major metabolite of dopamine is homovanillac acid (HVA), which is best collected in cerebrospinal fluid (CSF) via a lumbar puncture.
Owen & Simpson (1995) found normal levels of metabolites in the CSF of schizophrenics.
Bird et al. (1979) carried out postmortems and found that those with schizophrenia have an increased number of dopamine-receiving cells in parts of the limbic system.
Wong et al. (1986) carried out PET scans on living schizophrenics prior to medication and found evidence for a more than twofold increase in D2 (dopamine) receptors compared to controls.
Farde et al. (1990) carried out PET scans, as above, and found not significant differences between schizophrenics and controls. Different methodological approaches used by different researchers may have been why.
Evaluation of The Dopamine Hypothesis
Complications of medication: Many postmortem studies on schizophrenics pose a problem for researchers, because patients are likely to have taken neuroleptic drugs for their disorder when alive. Therefore, excess dopamine cells could be the result of medication rather than the cause of schizophrenic behaviour.
Cause and effect: When looking at the brains of schizophrenics, we cannot be sure whether changes are the cause or the result of schizophrenia. The only way to answer this question would be to scan people at risk of developing schizophrenia, but this would be expensive and unethical. It seems that we cannot discover the exact relationship between dopamine and schizophrenia until we are better at identifying the early stages of the disorder.
Dopamine cannot be the sole cause: A main source of evidence for the dopamine hypothesis is that dopamine-reducing antipsychotics reduce positive symptoms in schizophrenics; however they are only effective for around 75 per cent of patients. As 25 per cent are not aided by dopamine-lowering drugs, there must be another cause of their disorder.
Negative symptoms and glutamate: The negative symptoms of schizophrenia seem to involve a type of glutamate receptor called NMDA receptors. NMDA is involved when people take the drug PCP, abuse of which causes the onset of positive schizophrenic symptoms. This tells us that the relationship between dopamine and glutamate is crucial in the development of schizophrenia, and that the dopamine hypothesis is reductionist in its focus solely on a single neurotransmitter.
First-degree relatives (parents, siblings and offspring) share an average of 5o per cent of their genes, and second-degree relatives share approximately 25 per cent. To investigate genetic transmission of schizophrenia, studies look at concordance rates between family members.
Kendler et al. (1985) have shown that first-degree relatives of those with schizophrenia are 18 times more at risk of developing schizophrenia than the general population. Since family members share the same environment, however, it is difficult to determine whether this concordance is due to shared nature or nurture.
Another issue with family studies is their use of retrospective data, looking at people who have already been diagnosed. a prospective study would provide more reliable data because it can make comparisons before and after signs of illness.
Kety et al. (1994) conducted The Copenhagen High-Risk Study, which was a prospective, longitudinal study that began in 1962. They studied 207 offspring of schizophrenic mothers (high-risk group), compared to a matched control group of 104 children of ‘healthy’ mothers (low-risk group). By 1993 Schizophrenia was diagnosed in 16.2 per cent of the high-risk group, compared to 1.9 per cent of the low-risk group. This strongly supports a familial link with the disorder.
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 non-identical (DZ) twins. Both share the same environment, but only the MZ twins have identical genetic make-up.
Gottesman et al. (1987) found a 44.3% concordance rate for monozygotic (MZ) twins, 12.1% for dizygotic (DZ) twins and 7.3% for siblings.
To separate out genetics exclusively from the environment, researchers have sought out MZ twins reared apart, where at least one twin has schizophrenia.
Gottesman and Shields (1982) used the Maudsley twin register and found 58 per cent (7 out of 12 MZ twin pairs reared apart) were concordant for schizophrenia.
However, even in the rare cases where MZ twins are reared apart, they still share the same environment in the womb before birth, so environmental factors cannot be entirely discounted.
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 biological and adoptive parents.
Tienari (1969) Finnish Adoption Study: This began in 1969 when the researchers identified adopted-away offspring of biological mothers who had been diagnosed with schizophrenia (high-risk, 112 cases), plus a matched control group of 135 adoptees, whose biological mothers had not been diagnosed with schizophrenia. All had been separated from their mothers before the age of 4. The study reported that 7% of high-risk adoptees developed schizophrenia, compared to 1.5 per cent of controls.
Kety et al. (1994) The Danish Adoption Study: Found high rates of diagnosis for chronic schizophrenia in adoptees whose biological parents had the same diagnosis, even though they had been adopted away by ‘healthy’ parents.