Children of older fathers more likely to develop schizophrenia: NHRI study

Taipei, May 5 (CNA) Scientists in Taiwan have used genome sequencing to show that men who become fathers at a later age are more likely to pass along new mutations that put their children at a higher risk of developing schizophrenia.

The study, conducted by researchers at the National Health Research Institutes (NHRI) and National Taiwan University, was published in the scientific journal Molecular Psychiatry in March.

At a press conference Monday, NHRI Vice President Wei J. Chen (陳為堅) said that while the risks of geriatric pregnancies are widely studied, there has been comparatively little research on how paternal age affects children's health.

Wang Shi-heng (王世亨), an assistant researcher at the NHRI's National Center for Geriatrics and Welfare Research, explained that the NHRI had previously examined links between paternal age and schizophrenia by analyzing over 7 million Taiwanese medical records.

It found that children whose father was aged 25-29 at the time of their birth had a 0.5 percent chance of developing schizophrenia during their lifetimes, while those born to fathers aged 50 or above had a 1 percent chance, Wang said.

In cases where the grandfather on either side of the family was also at an advanced age when the child's father or mother was born, there was an even higher risk of the child developing schizophrenia, he said.

Wang said that two explanations have been offered for why this occurs, with the first being that men with a higher risk of mental illness simply happen to marry and have children at a later age.

A second hypothesis is that because men's sperm cells are continuously produced throughout their lives, and each division carries a higher chance of errors leading to new gene mutations, older fathers are more likely to pass the relevant mutations on to their children, he said.

This latter explanation is bolstered by other factors, including evidence that an increased number of rare mutations is associated with a higher risk of schizophrenia, and that men pass on four times as many new genetic mutations as women, he said.

In an effort to prove a causal relationship, the NHRI team performed whole-genome sequencing on five Taiwanese families, each comprising three siblings affected by schizophrenia and two healthy parents, Wang said.

They found that for every year a man delayed having children, their child had 1.5 times more de novo, or new, gene mutations. Moreover, the more such mutations a child had, the earlier in life they began to experience symptoms of schizophrenia, Wang said.

In quantifiable terms, the team's analyses showed that 30 percent of the observed association between paternal age and the onset age of schizophrenia might be mediated by paternal age-related mutations, while the other 70 percent is attributable to their family and social environment, Wang said.

Chen, meanwhile, noted that previous NHRI research has shown that a paternal age below 20 is associated with multiple other risks for the child.

Taken together, these studies highlight the importance of government policies that encourage couples to have children at a suitable age, he said.

In Taiwan, the average age of mothers at childbirth has risen by 5.2 years, from 27.2 to 32.4, between 1991 and 2023, while the average age of fathers rose by 4.3 years, from 30.3 to 34.6, Interior Ministry data shows.