Genetic risk necessary and sufficient

Family aggregation of schizophrenia is at present the only epidemiologically well-established risk factor for the disorder, with a relative risk for first-degree relatives of schizophrenics in the range from 9 to 18. Allowing for diagnostic variation, the risk estimates generated by different studies are similar and suggest a general pattern of descending risk as the proportions of shared genes between any two individuals decrease. (79) The weight of the evidence also suggests that genetic vulnerability is necessary but not sufficient to cause schizophrenia and that environmental factors must play a role. However, the evidence for an environmental contribution to the aetiology of schizophrenia remains indirect, stemming primarily from the observation that the concordance for schizophrenia in monozygotic twin pairs is only about 50 per cent. Three general models of the joint effects of the genotype and the environment have been proposed: (89

1. the effects of predisposing genes and environmental factors are additive and increase the risk of disease in a linear fashion;

2. genes control the sensitivity of the brain to environmental insult;

3. genes influence the likelihood of an individual's exposure to behavioural pathogens, for example by fostering some personality traits.

Current epidemiological research into possible environmental causes of schizophrenia focuses on three main areas: pre- and perinatal damage, factors affecting early brain development, and factors operating at the level of the social and family environment. (See also Ch.a,p.t§L.4,.3.5...1.)

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