de Kluiver · American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2017 · narrative review · n=?

Paternal age and psychiatric disorders: A review.

Cited 103 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing epidemiological hypotheses and mechanisms without systematic review methodology

PubMed 27770494 · doi:10.1002/ajmg.b.32508 · record verified 2026-08-26

What was done

The authors reviewed epidemiological studies examining associations between paternal age at childbearing and psychiatric disorders in offspring (autism spectrum disorder, attention deficit/hyperactivity disorder, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and major depressive disorder). They evaluated four primary non-mutually exclusive explanatory hypotheses: de novo mutations, epigenetic alterations, selection into late fatherhood, and environmental resources.

What was found

The abstract reports no numerical estimates or effect sizes. Advanced paternal age showed the most robust epidemiological associations with autism spectrum disorders and schizophrenia. Individual studies reported either a monotonic increase in risk across paternal age or a marked risk increase beyond a specific age threshold. The authors noted supporting evidence for both the de novo mutation hypothesis and the selection into late fatherhood hypothesis, but the underlying mechanisms remain unclarified.

Why it matters

This review synthesizes the evidence linking older paternal age to psychiatric vulnerability in offspring and outlines the competing biological and behavioral mechanisms proposed to explain the effect.

Limits

The abstract provides no quantitative data, odds ratios, or sample sizes. As a narrative review rather than a systematic review or meta-analysis, formal search criteria, study counts, and synthesis methods are not detailed. Disentangling biological aging effects from genetic selection factors predisposing to delayed fatherhood remains unresolved in the literature.

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