Twin Studies

Twin studies offer further evidence that genes and environment are implicated in the development of schizophrenia. The chances of becoming schizophrenic are roughly 50% if one's identical twin has the disorder [14] and 12% if one's non-identical twin has it [51]. Lack of complete concordance is typically attributed to environmental factors such as obstetric complications, family factors and other psychosocial stressors. Guidry and Kent [52] define environment more broadly to include that of the developing nervous system. They suggest that lack of complete concordance may be related to the inheritance pattern: ''Schizophrenia may be explained parsimoniously by a germline mutation in a gene related to neurodevelopment, followed by a somatic mutation during brain development'' [52]. This theory is thought to account for the variability in symptom expression, from mild symptoms to spectrum disorders to full-blown schizophrenia, in the relatives of schizophrenic patients. Other data suggest that being in a family where there are dizygotic twins is associated with an increased rate of schizophrenia in their relatives [53]. Klaning et al. [53] suggest that the same genes involved in dizygotic twinning may be involved in the transmission of schizophrenia. In their investigation of Danish subjects, they found a 35% increase in the rate of schizophrenia in the siblings of dizygotic twins whereas rates in relatives of monozygotic schizophrenic persons were comparable to that seen in siblings of singletons with the disorder [53].

While twin studies have provided a unique opportunity to assess genetic diathesis in the development of schizophrenia, an extraordinary group of monozygotic female quadruplets, all concordant for schizophrenia, have been the subject of a 39-year investigation [7]. The likelihood of four monozygotic twins all developing schizophrenia has been estimated by Rosenthal to be about one in 1.5 billion [54]. Despite identical genetic endowment, the onset and severity of their symptoms was highly varied. The Genain quadruplets, Nora, Iris, Hester and Myra, grew up in a midWestern town in the USA where they were local celebrities as children, singing and dancing under the watchful eye of their mother [6]. Their father, who exhibited odd behaviour, intrusiveness, illogical thinking and suspiciousness, is the suspected genetic contributor to the girls' schizophrenic illness [6]. In 1963, Rosenthal published an extensive review of the family's history and functioning [54]. Since then various follow-up studies have been published, most recently in 2000. This report included data gathered when the quadruplets were 66 years old [7]. Because of significant dementia, Iris could not be tested during the most recent follow-up, but Nora, Myra and Hester were able to participate. Using neuropsychological data gathered at age 27 and 51 for comparison, it appeared that cognitive performance was generally stable, and in some cases improved, at age 66. Of all the sisters, Myra's illness was perceived to be the least severe. She had the most education, was the only sister to marry, had two children, and showed signs of illness at a later age [7]. Mirsky et al. [7] reported that, at age 66, Myra showed the best performance on 6 of 13 neuropsychological measures, including the WCST. Hester, who was assumed to have the most severe form of schizophrenia and showed prodromal symptoms as early as age 11, had the lowest scores on 5 of the 13 measures, including the WCST [7]. Compared to their mean performance at age 27, the women all showed some improvement in their scores on the Continuous Performance Test (CPT), a measure of sustained attention, suggesting that the symptoms of schizophrenia are not necessarily chronic and unremitting [7]. As of this writing, Iris and Hester have died, both in their early 70s, and Nora and Myra continue to live in the community where they were born.

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