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Mental Illness Multiplied in Children

What are the odds of being mentally ill if both your parents have bipolar illness or schizophrenia? Extremely high, according to the results of a new long-term study. The find may help scientists better understand patterns of transmission of psychiatric illness.

No one knows what genes predispose people to schizophrenia or bipolar disorder, which each afflict about one in 100 people. There have been many candidates, but just what they do and how they interact is still largely a mystery.

Interested in how these diseases travel through families, professor emeritus and psychologist Irving Gottesman of the University of Minnesota, Twin Cities, and colleagues in Denmark turned to the Danish Psychiatric Central Register. The team analyzed the records of all psychiatric admissions in the country between 1970 and 2007 and found 196 pairs of parents in which both had been diagnosed with schizophrenia. Of the 270 offspring, 27% had been admitted with a diagnosis of schizophrenia by the age of 52. And for all psychiatric diagnoses, hospitalization for this group was a whopping 67.5%. In contrast, among 8000 couples in which one spouse had schizophrenia, only 7% of the offspring were schizophrenic.

The team noticed a similar trend with bipolar disorder. Thirty-six percent of children of two bipolar parents had major depression, with two-thirds of those also being bipolar. And in a few couples in which one was schizophrenic and the other bipolar, 27% of the children were diagnosed with one or the other disease, the authors report in the March issue of the Archives of General Psychiatry.

The study, with its exceptionally large sample sizes, is "a major advance," says David Goldman, chief of the lab of neurogenetics at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland. Ordinary "additive" effect of whatever genes are involved can't explain the remarkably high risk, says Goldman. Rather, he says, the most likely explanation is a phenomenon known as epistasis, where genes can interact so as to greatly multiply an effect.

Schizophrenia researcher Daniel Weinberger of the National Institute of Mental Health in Bethesda agrees that the paper adds to evidence that epistasis—which has been shown in model organisms such as yeast but difficult to prove in humans—is "robust and ubiquitous." However, he adds that "having two parents who are seriously psychiatrically ill" may also tip the balance of sanity in a vulnerable son or daughter, regardless of their genes.

The authors say a better evaluation of risks of transmitting mental illness should be helpful to genetic counselors advising people on family decisions.