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Four Sisters With Schizophrenia, Four Decades of Scrutiny

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He notes that the Genains' father was a harsh and brutal man who treated Myra and Nora preferentially, expecting more of them and thereby hastening their intellectual and emotional development. In contrast, he was cruel and hostile to Hester and Iris, Mirsky reports.

Mirsky says the observation shows that while such psychosocial trauma cannot cause schizophrenia, it may account for the different course the disease takes in different people. "You can make the condition worse by mistreatment," he says. "You can't make someone schizophrenic, but you can make them worse. The genetic endowment can be modified by environmental experience."

E. Fuller Torrey, MD, executive director of the Stanley Foundation for Research Programs in Bethesda, MD, who reviewed the recent follow-up report on the Genains, said it confirms that the clinical course of illness varies from individual to individual. The Stanley Foundation is a nonprofit organization supporting research on schizophrenia and bipolar disorder.

While Torrey acknowledges the role of genes in predisposing an individual to schizophrenia, he believes they are not necessarily decisive. "We all agree there are genes involved," he tells WebMD. "The strength of that involvement is what we argue about."

Like Mirsky, Torrey acknowledges that some other factor -- he calls it "Factor X" -- must interact with the genetic predisposition to cause schizophrenia. But if there is disagreement about the strength of the role of genes, there is also no complete consensus on what Factor X might be, Torrey says.

Torrey does not believe that psychosocial trauma -- of the kind suffered by some of the Genains -- is a contributing factor in schizophrenia. "There is no data to support that at all, except on a theoretical basis," Torrey says.

Rather, he believes the important interactive factor is "almost certainly biological," and not related to their psychological makeup, or experiences. Specifically, he believes the genetic predisposition is probably complicated by a biological insult that occurs before the child is born, resulting in a neurological deficit causing the symptoms of schizophrenia.

Richard Wyatt, MD, chief of the neuropsychiatry branch at the National Institute of Mental Health, who also reviewed the report, says Mirsky's follow-up, and the entire history of Genains research, has an important lesson for doctors, researchers, and patients and their families. "It tells us that you can have clones of the disease but have different manifestations according to the different ways the genetic vulnerability meets the environment," Wyatt tells WebMD. "What it doesn't tell us is where the deviation occurs."

Regarding the effects of psychosocial trauma on the sisters, Wyatt says he can't disprove its relationship to the course of schizophrenia. "But I don't have much faith in it," he says.

Wyatt, like Torrey, believes the weight of research is leaning toward something harmful occurring when the child is in the womb, in combination with a genetic vulnerability. Specifically, he cites evidence of infection in the second trimester of pregnancy -- a critical period when important structures of the brain are formed.

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