Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study.
Axel Krug, Markus Wöhr, Dominik Seffer and 21 others
PMID 32576230WHAT IT FOUND
In healthy adults, having an older father was linked to higher neuroticism and schizotypal traits, plus larger right hippocampus and frontal brain volumes.
In rats, advanced paternal age caused social communication deficits and repetitive behaviors, mirroring autism symptoms.
Key findings
01In a sample of 677 healthy adults, paternal age was positively correlated with neuroticism and schizotypal personality traits.
02Paternal age was associated with increased gray matter volume in the right hippocampus and right inferior frontal gyrus in humans.
03Rats born to older fathers displayed social-communication deficits, repetitive behaviors, and early anxiety, consistent with an autism-related phenotype.
STILL TO COME
How it was doneWhat they found
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What it does not show
The human cohort consisted mostly of university students with high estimated verbal IQs, which may limit generalizability to the broader population. Brain imaging results in humans were not corrected for multiple testing, increasing the risk of false positives. The genome-wide methylation analysis had a small sample size (N=21), which may have been underpowered to detect significant epigenetic changes. The study was cross-sectional for humans, so it cannot establish causality between paternal age and the observed traits. Discrepancies were found between human blood and rat brain microRNA expression, complicating the interpretation of underlying molecular mechanisms.
Declared interests
The study was funded by the Deutsche Forschungsgemeinschaft and ERA-Net Neuron. No other conflicts of interest were declared.
The easy way to misread this
Do not assume that advanced paternal age directly causes autism or that these brain and personality findings apply to diagnosed patients. The human data comes from healthy students, and the rat model shows specific behavioral changes that do not necessarily translate to clinical diagnoses in humans.