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Four Sisters With Schizophrenia, Four Decades of Scrutiny

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It is an observation that has profound meaning for researchers. And despite much consensus in the field, there remains wide disagreement about how to explain the different outcomes of people who have schizophrenia, Mirsky and other experts tell WebMD.

Mirsky says that because they have exactly the same genetic makeup, the Genains are confirmation of the widely acknowledged fact that genes are necessary to "predispose" an individual to schizophrenia. But he believes the sisters' experience also points to the fact that a host of other variables -- including the treatment they received at the hands of their parents -- can have a role in the different courses their disease has taken.

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.

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