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.
Ultimately, schizophrenia may prove to result from an extraordinarily complex interaction of genes, biology and environment, continuously over time, says Irving Gottesman, PhD, the Sherrell J. Aston professor of psychology at the University of Virginia in Charlottesville.
The follow-up study of the Genains "continues the tradition in schizophrenia research of demonstrating that it is inaccurate to push for an exclusive genetic, biological or environmental point of view as being sufficient to account for what we see in schizophrenia generally, or in the Genains in particular."
For this reason, study of the four sisters may carry lessons beyond understanding schizophrenia. The factors that contribute to the disease -- genes, biology, psychosocial factors and the random events of life itself -- are what also contribute to normal development and personality, he says.