Men who are relatively older at their first child's birth may be more likely than younger first-time dads to have a child who eventually develops schizophrenia, hint results of a large Danish study.
Using data on more than 2 million people born in Denmark between 1955 and 1992, researchers found a link between first-time fathers' age and the odds of any of their children developing schizophrenia.
In contrast, the connection was not seen among fathers who were relatively older only when their second- or later-born child came into the world.
The findings, published in the American Journal of Psychiatry, add another layer to the relationship between parents' age and children's schizophrenia risk.
It's known that schizophrenia is a disorder of disrupted brain development, and researchers have long believed that it arises from a combination of genetic susceptibility and environmental factors - with the suspects including viral infections or poor nutrition during pregnancy.
A number of studies have also shown a relationship between parents' age at the time of a child's birth and that child's risk of developing schizophrenia.
However, most have suggested that the link to mothers' age is largely explained by fathers' age.
Researchers have speculated that the explanation might rest in the fact that older fathers are more likely than younger ones to have genetic abnormalities in their sperm, possibly including genetic abnormalities related to schizophrenia.
Doubt on previous theories
However, the new findings cast doubt on that theory, according to lead researcher Dr Liselotte Petersen, of Aarhus University in Denmark.
If the theory were correct, then fathers' age at the birth of any child, not just the first one, should be related to schizophrenia risk.
Instead, Petersen and her colleagues say, the findings give support to another theory: that men who have a predisposition to schizophrenia, but do not themselves develop it, tend to have children later in life than other men.
However, the reasons for such "delayed fatherhood" remain unknown, Petersen said.
One question, she said, is whether there could be factors, genetic or environmental, that both impair a man's fertility and contribute to schizophrenia risk in his children.
Another possibility is that men predisposed to schizophrenia are more likely to have personality traits that affect their relationships and make it more difficult to find a partner.
The vast majority of children born to relatively older fathers will not develop schizophrenia, as the disorder is estimated to affect 1% of the population.
However, a better understanding of the relationship between paternal age and schizophrenia risk could help uncover some of the causes of the disorder, Petersen said.
For the current study, she and her colleagues used data from Denmark's national system of registers to track more than 2.2 million citizens born between 1955 and 1992. Between 1970 and 2007, just over 14,200 of those individuals were diagnosed with schizophrenia.
They found that the odds of a child developing schizophrenia tended to increase in tandem with a father's age, but only his age at the birth of his first child.
Among fathers who were between the ages of 25 and 29 when their oldest child was born, there were 2,420 cases of schizophrenia among their 448,538 children, a rate of about 0.5%.
The corresponding rate was 0.7% among fathers who were in their 30s when their first child was born, just under 1.2% for fathers in their 40s, and 2% for those aged 50 or older at the birth of their first child.
Family history of mental illness did not explain the connection between first-time fathers' age and their children's odds of developing the disorder.
Researchers do not know why fathers' age, but not mothers', has been consistently connected to schizophrenia risk, according to Petersen.
"In future studies," she said, "we will search for factors that are associated with delayed fatherhood in order to understand and explain the effect of paternal age on schizophrenia risk."
(Reuters Health, Amy Norton, October 2010)