How twin and adoption studies attempt to distinguish genetic

Explain how twin and adoption studies attempt to distinguish genetic and environmental factors underlying the onset of schizophrenia within families. Review the studies and discuss two limitations of this. Schizophrenia is the label applied to a group of disorders characterised by severe personality disorganisation, distortion of reality, and an inability to function in daily life. Symptoms are mainly disturbances of thought processes, but also extend to disturbances of emotion and behaviour. There are two symptom categories – acute schizophrenia characterised by positive symptoms, uch as hallucinations and delusions; and chronic schizophrenia, characterised by negative symptoms such as apathy and withdrawal.

However, DSM-IV has now moved away from these definitions and classified schizophrenia into three main sub-types: paranoid, disorganised and catatonic. Understanding Schizophrenia More research has, probably, been devoted to trying to understand the nature of schizophrenia than any other mental disorder. Somatogenic approaches have focused on the role of genetic mechanisms influencing the propensity to develop schizophrenia, while psychogenic pproaches emphasise the effect of adverse childhood experiences, particularly abnormalities in family interaction in the aetiology of the disorder. Twin studies Twin studies offer a powerful method of disentangling the effects of genetic and environmental factors underlying the onset of schizophrenia within families.

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Monozygotic (MZ) twins have almost identical genomes, while Dizygotic (DZ) twins share only approximately half their genes. However, both usually share the same rearing environment. Thus, if environmental factors entirely explain familial lustering there should be no differences in the concordances between MZ and DZ twins. Conversely, if genetic factors are important, the concordance should be higher among MZ than DZ twins. If genetic factors alone were sufficient determinants, there should be a 100% concordance among MZ twins. In a Finnish study, the heritability of schizophrenia was 83% if first-degree relatives had been diagnosed with the disorder, the remaining 17% of the variance in liability was due to unique environmental factors; while common environmental factors seemed to have no influence on the liability (Cannon et al,1998).

The concordance was 46% among MZ twins and 9% among DZ twins. The results from a British study were almost identical. The concordance was 41% among MZ and 5% among DZ twins (Cannon et al, 1999). The importance of genetic factors also emerged in two studies that investigated the risk of schizophrenia among offspring of identical twins discordant for schizophrenia (Gottesman et al, 1982, Kringlen and Cramer, 1989). In the Danish twin study there was no significant difference in the risk of schizophrenia between offspring of affected twins (10%) and unaffected co-twins (17%) (Gottesman et al, 1982).

However, sample sizes were quite small: three schizophrenic twins had a total of 14 offspring, 1 of whom was affected; while 6 unaffected co-twins had 24 offspring, 4 of whom were affected. The sample size in the Norwegian twin study was larger (Kringlen and Cramer, 1989). Of the 28 offspring of schizophrenic twins, five (18%) developed the disorder; whereas 2 of the 45 offspring of unaffected co-twins had schizophrenia. These differences were not statistically significant. Although both of these studies lacked statistical power, they suggest that unaffected MZ co-twins tend to arry the genotype predisposed to schizophrenia; but that it remains unexpressed in them – for example, because they have not been exposed to environmental risk factors (Gottesman et al, 1982).

Twin studies, in summary, suggest that genetic factors are the most important risk factors for schizophrenia. However, environmental factors are also important, as less half of individuals with an identical genome – identical twins- are concordant for schizophrenia. Adoption Studies Adoption studies compare the effect of different rearing environments among groups that are assumed to be similar in their enetic predisposition, and the effects of different genetic predispositions among groups that are assumed to have similar rearing environments. In the adoptees’ family design, the group of adoptees who have developed schizophrenia in adulthood and unaffected control adoptees are compared.

The psychiatric status of the biological and adoptive relatives is investigated. If genetic factors are important,, the rate of schizophrenia should be higher among the biological than adoptive relatives of an affected adoptee. If the rearing environment is important, more abnormalities should be observed among the adoptive amilies of affected than unaffected adoptees (Gottesman and Shields, 1982). The largest study to use the adoptees family design was the Danish adoption study of schizophrenia (Kety, 1983). This found significantly increased risks of developing DSM-III schizophrenia among biological relatives of suffers than among relatives of the control group. However, there was no increased risk among adopted relatives of affected vs. control (Kety, 1983, Kendler et al, 1984). The Finish adoption study of schizophrenia (Tienari et al, 1994) confirmed the genetic contribution in schizophrenia;84% of the adopted ffspring with schizophrenia developed a non-affective psychotic disorder, compared with only 0. 5% of the adopted offspring of control groups (Tienari et al, 1994). However, a gene-environment interaction also emerged in the study (Wahlberg et al, 1997).

When the adoptees were tested for schizophrenia at the mean age of 21, only those adoptees whose biological mother had, had schizophrenia and whose adoptive parents showed high level of communication deviance displayed schizophrenia. This was not observed among adoptees who had only a biological mother with schizophrenia or adoptive parents with a igh level of communication deviance (Wahlberg et al, 1997). Adoption studies confirm the importance of genetic factors in the aetiology of schizophrenia – the Finish adoptive study has provided evidence for gene-environment interaction in the development of schizophrenia. Family Studies Psychoanalytic theories have considered disturbed early interaction between parent and child to be an important factor in the development of schizophrenia (Allen, 1976).

In the 1946 British cohort study, mothers of children who later developed schizophrenia had worse average general understanding and management of their children, lthough none of them was known to be mentally ill (Jones, 1983). In the Northern Finish 1966 birth cohort, being a child of an unwanted pregnancy was significantly associated with the later onset of schizophrenia (Myhrman et al, 1996).

However, being from a single-parent family was not associated with the risk of developing schizophrenia or other psychotic disorders (Makikyro et al, 1998). Thus, as a result of vast genetic research, family environment has been seen as less and less important. Conversely, the possibility that the childhood rearing environment might be a risk factor for – or a rotective force against – the later development of schizophrenia should not be discarded. Limitations Of The Studies These studies have divided the opinion of researchers. Some regard the findings as unreliable, caused entirely by the operation of confounding factors, such as narrowing diagnostic criteria; while others believe them to be genuine indicators of the underlying factors affecting the onset of schizophrenia within families. The problem of mechanism of action and interactions of genetic and environmental risk factors is common to all aetiological research on complex diseases (Ottman, 1996).

Limitation 1:Genetic Factors Twin studies provide evidence of a genetic contribution to schizophrenia: if one identical twin gets the disease, the other has approximately a 30-40% chance of getting it (with a mean delay of 4 years); even if the two have been brought up in different families. Nevertheless, the shared genes of identical twins are not sufficient to give rise to schizophrenia in all instances; i. e. concordance for MZ twins is not 100% and a `schizophrenia gene` has not been identified despite extensive genome mapping programmes, pointing to the participation of other factors.

Limitation 2:Environmental Factors People with schizophrenia may display a variety of patterns of aberrant behaviour, raising the possibility that each pattern reflects a different form of the disorder – due to a different cause. However, even MZ twins who both have schizophrenia, and who are presumed to have been afflicted because of shared environmental factors, often have different patterns of symptoms. Therefore, the variability in symptoms does not appear to be a basis for distinguishing between schizophrenia within families due to genetic or environmental causes.

Both genetic and environmental factors have been shown to be important in the aetiology of schizophrenia. Thus, accounting for different aspects of the disorder. However, adopting Gottesman and Shields (1982) combined model of schizophrenia, in which the majority of causes would be attributed to a combined effect of genetic and environmental factors, would seem wise until proved otherwise. Consequently, it can be concluded that genes do not act alone to cause schizophrenia. Environmental factors are also important, although the exact nature of either of their roles is not yet fully established.

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