Study Addresses Schizophrenia Link

LA Times Thursday April 12, 2001

AP Medical Writer

CHICAGO--Older fathers are much more likely than younger ones to have children with schizophrenia, a study suggests, adding mental illness to the list of diseases linked with advancing paternal age.
     While previous research has suggested children of older fathers are at risk for certain cancers and birth defects, the study is the first to make the link with a psychiatric illness, said Dr. Dolores Malaspina of Columbia University and the New York State Psychiatric Institute.
     In the study, men who fathered children at ages 45 to 49 were twice as likely as those under 25 to have schizophrenic children, and men 50 and older were three times more likely.
     The researchers, led by Malaspina, reviewed data on 87,907 people born in Jerusalem from 1964 to 1976. Their findings appear in April's Archives of General Psychiatry.
     "I would guess that our study is just the tip of the iceberg," said co-author Dr. Susan Harlap of New York University School of Medicine. "Eventually it would seem that the father's sperm is going to turn out to be just as important as the mother's egg."
     During their lifetimes, men's sperm cells continue to reproduce by dividing. Each time this process occurs, there is a slight risk of genetic defects. By the time a man is 20, his sperm cells have undergone about 200 divisions; by age 40, about 660.
     Women's eggs do not reproduce, but the eggs they are born with are subject to effects of aging. They may develop chromosomal abnormalities, such as the defect that causes Down syndrome.
     But Dr. Michael Watson, executive director of the American College of Medical Genetics, said those defects tend to involve larger structural cell changes, which are more easily detected through genetic testing than sperm mutations.
     Watson said the new study is not surprising, since "there are a whole class of diseases inherited in the same way as schizophrenia where there's a paternal age effect."
     These include prostate and nervous system cancers; dwarfism; and Marfan syndrome, which causes a gangly appearance and often features skeletal and heart abnormalities.
     Schizophrenia occurs in about 1 percent of the population. It is thought to be caused by a combination of genetic and environmental factors.
     The findings may help researchers zero in on the causes, Malaspina said.
     They also may explain the steady prevalence of the disease, showing how new mutations in each generation keep the incidence stable, the researchers said. The study was funded by the National Institute of Mental Health and the G.Harold and Leila Y. Mathers Charitable Foundation.