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Schizophrenia in Offspring
Linked to Father's Age

NEW YORK (Reuters Health) - Women may hear the symbolic ticking of their biological clocks as they approach the age of 40, but men might want to listen more closely to their own, researchers suggest.

A recent study found that fathers aged 50 and older were nearly three times more likely than men younger than 25 to have a child with schizophrenia. Men aged 45 to 49 were about twice as likely to have a child with the disorder, regardless of the mother's age.

The findings, published in the April issue of Archives of General Psychiatry, support previous studies demonstrating a link between older fathers and other gene-related disorders. If confirmed, they could shape strategies to search for genes that may play a role in schizophrenia, Dr. Dolores Malaspina of Columbia University in New York City and her colleagues write.

``Many genetic diseases are related to new mutations and paternal age, but this is the first demonstration of this effect for a psychiatric disease,'' Malaspina told Reuters Health in an interview. ``This suggests that many nonfamilial cases of schizophrenia, previously presumed to reflect a greater contribution of environmental causes, might instead be genetic.''

Schizophrenia is a severe brain disorder that alters a person's perceptions of reality, emotions and thought processes. Symptoms of the disorder, which affects about 1% of the world's population, typically surface during the late teens and 20s.

While the causes of the disease are not known, schizophrenia is believed to arise from a mix of genetic and environmental triggers. Exactly how the disease is passed along has remained unclear, since it can reduce the reproductive capacity of patients.

To investigate whether new mutations--rather than those passed from generation to generation--played a role, the researchers analyzed rates of schizophrenia among a group of nearly 88,000 children in relation to their parents' ages.

The risk of the disorder rose in tandem with the father's age but was not significantly tied to the age of the mother, results show. The rate of the disorder among children born to men younger than age 25 was 2.5 per 1,000 children. It rose to 4.4 per 1,000 children for fathers aged 35 to 40, and to 11.4 per 1,000 children for dads 50 and older.

The authors explain that in the process of constantly dividing, sperm-producing cells become more vulnerable to mutation. These mutations can be passed along to offspring.

``Each time a cell divides there is a chance for an error, and these errors accumulate in men as they age,'' Malaspina told Reuters Health.

She added that male sperm cells are copied every 16 days and undergo 200 divisions by age 20 and 660 divisions by age 40.

``If new mutations play a role in schizophrenia vulnerability then we would expect to observe a relationship between schizophrenia and paternal age,'' the authors explain.

The researchers estimate that one quarter of schizophrenia cases may be linked to paternal age, and for the offspring of fathers 50 and older, two thirds of cases may be attributed to paternal age.

SOURCE: Archives of General Psychiatry April 2001.

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