Children conceived by older men may be at greater risk for early-onset schizophrenia, a more severe form of the disorder, according to a new study published in the journal Biological Psychiatry. The link remained after taking into account both parents’ genetic predispositions for schizophrenia, suggesting that advanced paternal age itself contributes to the risk.
Although previous research has shown a link between advanced paternal age and an increased risk for schizophrenia, it has been difficult to disentangle the effects of age versus factors related to age.
For example, choosing to be a dad late in life reflects a father’s predisposition to schizophrenia, said senior author Dr. Wei J. Chen, M.D., National Taiwan University in Taipei. Maternal predisposition could also lead to late parenthood and increased risk in offspring.
But now, due to recent advances in technology, scientists can estimate a person’s total genetic risk for schizophrenia.
For the study, the researchers looked at the polygenic risk scores for the parents of over 1,600 people with schizophrenia to estimate the maternal and paternal predispositions to the disorder. Men who had their first child later in life tended to have increased polygenic risk for schizophrenia.
“After controlling for parental polygenic risk scores, every 10-year delay in paternal age increased the risk of early-onset schizophrenia in offspring by about 30 percent,” said lead author Shi-Heng Wang, Ph.D., China Medical University in Taichung. Maternal age was not associated with risk of early onset in offspring.
This finding suggests that paternal age itself plays an independent role in the increased psychiatric risk in offspring, rather than being associated with increased risk through other factors related to late parenthood.
The study defines early-onset schizophrenia as occurring before 18-years old, which tends to be a more severe form of the disorder and is associated with more genetic abnormalities. Patients involved in the research had healthy parents and no apparent family history of schizophrenia. These cases, referred to as sporadic, are thought to arise mainly from increased genetic mutations.
“Presumably, advanced paternal age increases risk for early-onset schizophrenia because advancing age is associated with an accumulation of mutations,” writes John Krystal, M.D., editor of Biological Psychiatry.
“These age-related mutations appear to be distinct from those more commonly associated with the risk for schizophrenia. It would be important to understand the distinct neural mechanisms through which advanced paternal age influenced the age of onset.”
Identifying these mechanisms is of particular concern as more men are having children later in life. The new findings provide an important advance regarding how the father’s age at conception can affect the offspring’s risk for schizophrenia.
Around 1 percent of the world’s population is affected by schizophrenia. Each year, about 1.5 million people will be diagnosed.