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Advanced paternal age effects in neurodevelopmental disorders-review of potential underlying mechanisms

M Janecka1,2, J Mill1,3, M A Basson4

  • 1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Translational Psychiatry
|February 1, 2017
PubMed

Insights

Advanced paternal age (APA) is linked to neurodevelopmental disorders in children. This review explores genetic and epigenetic factors, suggesting multiple mechanisms contribute to risks like autism and schizophrenia.

Area of Science:

  • Neurodevelopmental Biology
  • Genetics
  • Epidemiology

Background:

  • Epidemiological studies indicate a correlation between advanced paternal age (APA) and adverse neurodevelopmental outcomes in offspring.
  • Specific concerns include increased risks for autism and schizophrenia.
  • The precise mechanisms by which paternal age influences neural development remain unclear.

Purpose of the Study:

  • To review epidemiological and molecular findings on the association between APA and offspring neurodevelopmental disorders.
  • To present evidence for genetic and epigenetic mechanisms involved.
  • To discuss limitations in the current literature and propose a multidimensional etiological model.

Main Methods:

  • Review of existing epidemiological studies.
  • Analysis of molecular findings, focusing on genetic and epigenetic mechanisms.
  • Synthesis of evidence to evaluate different hypotheses.

Main Results:

  • APA is associated with increased risks for neurodevelopmental disorders.
  • Evidence points to both inherited predispositions and de novo events.
  • Genetic and epigenetic alterations in paternal gametes are implicated.

Conclusions:

  • The effects of APA are likely multidimensional, not attributable to a single cause.
  • Multiple mechanisms, including genetic and epigenetic factors, likely contribute to the observed risks.
  • The etiological complexity of neurodevelopmental disorders is reflected in the APA association.

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