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18 April 2001
Older Fathers Risk Children With Schizophrenia
by George Atkinson

While older women run a higher risk of having babies with birth defects, it has long been presumed that men could have healthy children at any age. Think again. A new study now shows that older fathers are far more likely to have children with schizophrenia, while the age of the mother appears to have no influence on the likelihood of her offspring developing this devastating disease.

The study showed a strong, steady increase in the risk of having children with the disease as men aged. Men aged 45 to 49 were twice as likely to have children with schizophrenia as men under the age of 25 who became fathers, while the risk tripled for men over the age of 50, according to an analysis of a large population of over 85,000 people by researchers from New York University School of Medicine, Columbia University College of Physicians & Surgeons, and Israel's Ministry of Health.

"Women are often made to feel responsible for problems occurring during pregnancy, especially if anything goes wrong with their children's health, but this new study shows that men also contribute," says Susan Harlap, M.D., Research Professor of Epidemiology in the Department of Obstetrics and Gynecology at NYU School of Medicine and an author of the new study.

"There has been some previous research showing that men contribute to rare genetic abnormalities in their offspring. Schizophrenia, by comparison, is common, affecting 1% of all populations worldwide," says Dr. Harlap. "I would guess that our study is just the tip of the iceberg. Eventually it would seem that the father's sperm is going to turn out to be just as important as the mother's egg."

The new findings, however, shouldn't deter older men from becoming fathers, says Dr. Harlap. "I don't think that older men should disqualify themselves from becoming parents. At any particular age, there is always a trade-off. Our study suggests that a man's progeny are going to be healthiest if he has his children during his early 20s. But we know that many men aren't ready for marriage and parenthood at that age. A man may want to wait until he is mature enough and economically stable enough to have children, even though there are health risks involved in having children at an older age."

The study, published in the April issue of the journal Archives of General Psychiatry, is the first time advancing paternal age has been linked to a psychiatric rather than a physical illness, says Dolores Malaspina, M.D., Associate Professor of Clinical Psychiatry at Columbia University College of Physicians & Surgeons and lead author of the study. "A man has a biological clock, too. Men should be aware of the risks when they do their family planning," she said.

Overall, the researchers found that 26.6% of the schizophrenia cases could be attributed to the dad's age. And for fathers over the age of 50, two out of three cases of schizophrenia among their children could be attributed to the effects of paternal age.

Schizophrenia is a devastating brain disorder and the most disabling of severe mental illnesses. It afflicts about 1.1 percent of adults or about 2.2 million people in the United States, according to the National Institute of Mental Health. About the same percentage are affected in countries around the world, which is one of the puzzles of the disease. If caused by environmental factors, then presumably the disease would only arise in certain parts of the world. No one knows what causes schizophrenia, but it is suspected that many genes contribute to it.

The researchers believe that the new study can explain why the incidence of schizophrenia remains fairly constant in all populations over time. They suggest that new mutations are being introduced at a constant rate in the disease genes. In older men, the cells that eventually become sperm have already divided hundreds of times. Each of these divisions, like a lottery, has been an opportunity for chance mutations to occur in one or more of the genes causing schizophrenia. On the other hand, a woman's egg cells divide only 24 times, and almost all the divisions occur during fetal life. So it is less likely that new mutations would be transmitted through a woman's egg.

The study used data assembled from two sources: a large population-based research database called the Jerusalem Perinatal Study and a national Israeli registry of psychiatric disease. The psychiatric registry, established by the Ministry of Health in 1950, receives information about all psychiatric illnesses, including reports from patients admitted to psychiatric wards within general hospitals and psychiatric day-care facilities. The Jerusalem Perinatal Study at Hebrew University surveyed the health of more than 90,000 children born in Jerusalem from 1964 to 1976. Both databases are strictly confidential and the research team in the U.S. was allowed access to the files only after the names and other identifying information had been removed.

Of the 1,337 individuals in the study who were admitted to psychiatric units before 1998, 658 were diagnosed with schizophrenia and related psychoses, according to the study. After controlling for a number of factors (a statistical method that adjusts certain variables to reveal associations), including maternal age, the researchers found that paternal age was strongly associated with a diagnosis of schizophrenia, but not with the other psychiatric disorders.

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