Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study

Area of Science:

• Neuroscience
• Genetics
• Psychology

Background:

• Advanced paternal age (APA) is a known risk factor for neurodevelopmental disorders like autism and schizophrenia.
• The underlying biological mechanisms remain largely unknown.

Purpose of the Study:

• To investigate the neurobiological and behavioral correlates of advanced paternal age.
• To explore potential epigenetic and microRNA involvement in APA-related risks.

Main Methods:

• Correlational analyses of personality traits, brain structure (VBM), and white matter integrity (DTI) with paternal age in humans.
• Genome-wide methylation analysis in humans and microRNA profiling (miR-132, miR-134) in humans and rats.
• Behavioral assessments in an advanced paternal age rat model, including social interaction and anxiety.

Main Results:

• Paternal age correlated positively with schizotypy, neuroticism, gray matter volume in specific brain regions, and fronto-hippocampal connectivity.
• APA was associated with differential DNA methylation and altered expression of miR-132 and miR-134 in both species.
• APA rats exhibited social-communication deficits, repetitive behaviors, and increased anxiety.

Conclusions:

• Advanced paternal age is associated with significant alterations in personality, brain morphology, connectivity, and epigenetic regulation across species.
• These changes, potentially mediated by microRNAs and epigenetic mechanisms, may contribute to the increased risk of neurodevelopmental disorders observed in offspring of older fathers.