By the time the father is over 45, his risk of having a child who will develop schizophrenia is nine times higher than that of a 20-year-old father
Risk may increase, for example, with the age at which parents conceive a child. Although this is not the same type of genetic risk as the one just discussed, the cause of the increased risk is nevertheless genetic. Until recently, most attention focused on mothers over 40, who are known to be at higher risk of having children with diseases such as Down’s syndrome. It now appears, however, that it is not older mothers who are more likely to have offspring who become schizophrenic but rather older fathers. Regardless of whether they have a family history of schizophrenia, older fathers confer an increased risk of schizophrenia on their offspring. In fact, the risk to the offspring goes up steadily with the age of the father after age 24, independent of the age of the mother. By the time the father is over 45, his risk of having a child who will develop schizophrenia is nine times higher than that of a 20-year-old father. The most likely reason is that men are constantly developing new sperm. Because the precursors to sperm— spermatocytes—divide every 16 days, by the time a man is 55 years old, almost 1,000 cell divisions have taken place. The opportunity for a copying error in the sperm in which a mutation spreads through the generations of sperm by copying itself is, therefore, relatively high.
The contribution of a father’s increased age could explain a good number of the observations associated with schizophrenia. For instance, although schizophrenia clearly runs in families, it does not do so in a manner consistent with the classical genetics of Gregor Mendel. It can, for instance, appear in families where it has not been seen before. The risk attached to older fathers may be more apparent today. Probably a certain number of older men have always produced children, but having a large pool of older fathers healthy enough to have children in substantial numbers is a new phenomenon.