Biological explanations of schizophrenia

Sz appears to run in families, and controlled genetic studies (Gottesman, 1991) have shown that the risk for a particular individual developing sz is proportional to the amount of genes they share. 

• For MZ twins, the risk is 48%
• For DZ twins or children with one affected parent is 17%
• For grandchildren the risk is 5%
• For the general population, the risk is 1%

However, it is also clear that, even when the relative is genetically identical (MZ twin), the chance of developing sz is not 100%, suggesting other factors play an important part and two main methods have been used in an attempt to disentangle genetics and environmental factors: twin studied and adoption studies. 

A number of twin studies have been conducted and most show a higher concordance rate for MZ than DZ twins (Gottesman, 1991, Cardno, 2002 - 26.5% MZ, 0% DZ on the Maudsley Twin Register), but there are problems with this type of research:

• MZ twins are relatively rare in the population and of these, only 1% would be expected to have sz, so sample sizes in these studies are usually small. 
• Twin studies do not all use the same diagnostic criteria so comparisons cannot always be made. Different definitions product different concordance rates ( McGuffin, 1984)
• Concordance rates can also be calculated in different ways and vary widely depending on the method used. E.g. studies that have used 'blind' interviewers (i.e. people who are not aware of the diagnosis of patients) have found lower concordance rates than other studies. Marshall (1990) has suggested that the better controlled the study, the lower the concordance rate. 

It is difficult with twin studies to separate the effects of heredity from the effects of the environment because twins are usually raised together. Adoption studies allow researchers to look at people who were born to schizophrenic mothers but brought up by adoptive parents with no history of the disorder. Kety (1994) found high rates of sz in individuals whose biological parents had the disorder but who had been adopted by psychologically healthy parents. Tienari (1991), in the Finnish Adoption Study, identified 155 adopted children whose biological mothers had been diagnosed with sz. He compared them with a matched group of adopted children who had no family history of sz. He found about 10% of the adopted group with sz mothers developed sz, compared to the 1% of the control group. Studies such as these provide strong evidence for a genetic component in the development of sz. However, as with twin studies, there are methodological problems with some of the reported adoption studies which affect the validity of the findings. 

It does seem likely that there is a genetic component in sz, but that any pattern of inheritance is likely to be complex. 

A prospective, longitudinal study, Denmark, 1962. Kety et al identified 207 offspring of mothers diagnosed with sz (high risk group) along with a matched control of 104 children with 'healthy' mothers (low-risk) aged 10-18 at the start of the study, matched on age, gender, socio-economic status and urban/rural residence. Follow up were in 1974 and1989. Results supported a strong familial link with two psychotic disorders:

• Schizophrenia: 16.2% in high-risk group, 1.9% in low-risk 
• Schizotypal personality: 18.8% in high-risk, 5% in low-risk 
• Combining two results: 35% high risk, 6.9% low risk.

• + Prospective study looks at children before any symptoms appear and doesn't rely on any one's fallible memory=reliability. Kety was able to select p's appropriately and follow them accurately because of detailed life long records. The study longitudinal, important as sz can develop in individuals over the age of 40, although this is not that common. 
• + Children carefully matched on relevant variables. Low socio-economic status and urban environments known to be risk factors for sz. 
• - Cannot differentiate between genetics and environment in family studies. 
• - All mothers diagnosed with early criteria, may not have been with later criteria.

• In the Kety et al study, how are high and low participants differentiated? 
• What was the experimental design? 
• What is a prospective study? 
• Why was a longitudinal study advantageous in this case? 
• Is it that 'low socio-economic status and  urban environment' are risk factors for sz or the other way around? 
• Give one major problem with genetic explanations of sz in twins.

• High risk = offspring with mothers diagnosed with sz, Low risk = children with 'healthy' mothers
• Matched pairs
• Opposite of retrospective; looks at p's before symptoms
• Kety could follow the p's accurately because of detailed life long records. Also, sz can develop in individuals even over the age of 40 so observations over a short period of time could miss this. 
• Low socio-economic status and urban environments are risk factors
• Twin studies are not the perfect genes vs environment we would wish they were. 

Several neurotransmitters have been implicated in sz but the most promising line of research has focused on dopamine. According to the dopamine hypothesis, schizophrenia results from an excess of dopamine activity at certain synaptic sites. This could be caused either by the release of excess dopamine by presynaptic neurons, an excess of dopamine receptors or over-sensitivity of dopamine receptors. Support for the dopamine receptors hypothesis comes from various sources:

• Phenothiazines (drugs which act by blocking dopamine at the synapse) are affective in alleviating some of the major symptoms of sz. 
• Clozapine, a drug that is the one of the most clinically effective treatments for sz, was once thought to be weak at blocking dopamine receptors. However, PET scans have now shown that it occupies dopamine receptor sites to the same extent as other neuroleptic drugs.
• L-dopa (a drug used to treat Parkinson's disease) acts by increasing dopamine levels. It can produce symptoms of schizophrenia in previously unaffected individuals. 
• Amphetamines (stimulant drugs that act by increasing the availability of dopamine and noradrenaline in the brain) can induce symptoms of acute paranoid schizophrenia in previously unaffected individuals and increase the severity of symptoms in previously diagnosed cases of schizophrenia. 

Hope-Simpson (1981) found, since the late 1920s, there has been an overwhelmingly high proportion of people diagnosed with sz were born in winter and early spring

A number of viral infections, in particular, Influenza A have been suggested as an explanation - which is most prevalent in winter, if implicated in some way could explain the high proportion of winter births in those diagnosed with sz. The suggestion is that if the mother is infected during pregnancy, there is a pre-birth exposure in the Influenza A virus. It is thought that a 25-30 weeks old foetus is most vulnerable because of accelerated growth in the cerebral cortex at this time. It is hypothesized that the viral infection enters the brain and gestates until it is activated by hormonal changes in puberty.

• + Throughout history, peaks of sz diagnosis have corresponded with major flu epidemics.
• + Hare (1983) incidence of sz increased in C19 with urbanisation which precipitated infection. But with urbanisation came more hospitals and more awareness of cases
• Marcelis1998 high +correlation between urban birth and development of sz, associated with stress, divorce, noise, pollution, crime.
• Torrey (1988) claimed the link between sz and viral infections only occurs in those with a predisposition. However, if this were the case,100% of MZ and perhaps DZ concordance exp.

Torrey (1993) believes that sz may be the result of a virus affecting prenatal development, especially during the 2nd trimester, when the developing brain is forming crucial interconnections. In normal development, pre-alpha cells are formed in the middle of the brain and move to the cortex, but in sz, they only get 85% of the way. 

Bracha (1991) found one MZ who develops sz is more likely to have various hand deformities than the other twin. Since the hands are formed during the second trimester, the same prenatal trauma or virus that affects the brain, may affect the hands. 

Parker (2000) found there is little agreement over the plausibility of viral theories. The same influenza epidemic that affected Finland, England, Wales and Edinburgh was found absent in the rest of Scotland and the US in 1957. The virus that caused the epidemic could not have changed.