Health

Older fathers increase the risk of mental illness

New research finds that the age of fathers at the time of conception has an impact on children's risk of becoming mentally ill. The older fathers, the higher the risk.

By Mikkel Linnemann Johansson, , 6/10/2020

Previous studies have found a correlation between fathers' advanced age and their children's increased risk of having a mental disorder, most notably neurodevelopmental disorders, such as autism. Autism is characterized by social communication deficits together with repetitive and stereotypic patterns of behavior.

However, whether this is due to biology or the environment has so far been impossible to ascertain. Now, new research in rats has confirmed that the advanced age of fathers at the time of conception increases the risk for social communication deficits.

- Among people, fathers typically stay with their children. Therefore, it has not been possible to determine if their children's increased risk of having a mental illness is due to having grown up with an elderly father or whether the cause was biological. At the same time, researchers had difficulties to isolate paternal age when studying people, explains Associate Professor Markus Wöhr from the Department of Biology at the University of Southern Denmark.

Focusing on age

Together with other researchers, he has just published the results of a research project in which it has been investigated whether the increased risk is biological.

Through experiments with rats, they were able to design an experiment where it was possible to ensure that the only difference between the test group and the control group was the age of the fathers at the time of conception.

Here, rats from two groups were mated. In the test group, male rats were twelve months old at the time of conception. In the control group, male rats were two months old at the time of conception. In all cases, the female rats in the trial were two months old.

Because rat pups do not grow up with their fathers, it has been possible to rule out that the increased risk of social communication deficits is due to growing up with elderly fathers.

- We investigated whether the prevalence of social communication deficits was greater among the rat pups from the test group compared to the control group, says Markus Wöhr.

Measuring rat laughter

As in humans, here the challenge was that one cannot see whether a rat has a mental disorder through for example a blood sample.

However, the researchers could see a significant difference in the rat's vocal communication with each other.

- Rats produce high-frequency calls not audible to us humans that are believed to reflect positive affect, and presumably occur when rats are happy, excited or even experiencing euphoria, explains Markus Wöhr, who describes rats as very social animals.

The positive call is so characteristic that scientists call it rat laughter.

And here the difference was clear. The rat pups with young fathers used their positive calling to a greater extent when socializing with each other, while the rat pups with old fathers used their positive calling to a much lesser extent.

The experiments were carried out repeatedly. Each time with the same results and evidence that the rat pups with old fathers did not enjoy social interactions in the same way as the other rat pups.

- This confirms that it is the age of the fathers at the time of conception that makes a significant difference, says Markus Wöhr.

The brain is different

Examination of brain tissue from the two groups of rat pups also revealed neurobiological differences.

Here, it was found that two so-called microRNAs involved in neuronal plasticity processes were regulated very differently in the brains of rat pups with old fathers compared to the brains of rat pups with young fathers.

- Subsequently, we were able to investigate these two specific microRNAs in humans and found that they were affected by advanced paternal age as well, says Markus Wöhr.

- Because neurobiological differences in offspring with older fathers have been identified, a new potential also arises for treatment approaches for neurodevelopmental disorders, such as autism, in the future, he says.