Paternal age and psychiatric disorders: A review

Abstract

We review the hypotheses concerning the association between the paternal age at childbearing and childhood psychiatric disorders (autism spectrum‐ and attention deficit/hyperactive disorder) and adult disorders (schizophrenia, bipolar‐, obsessive–compulsive‐, and major depressive disorder) based on epidemiological studies. Several hypotheses have been proposed to explain the paternal age effect. We discuss the four main—not mutually exclusive—hypotheses. These are the de novo mutation hypothesis, the hypothesis concerning epigenetic alterations, the selection into late fatherhood hypothesis, and the environmental resource hypothesis. Advanced paternal age in relation to autism spectrum disorders and schizophrenia provided the most robust epidemiological evidence for an association, with some studies reporting a monotonic risk increase over age, and others reporting a marked increase at a given age threshold. Although there is evidence for the de novo mutation hypothesis and the selection into late fatherhood hypothesis, the mechanism(s) underlying the association between advanced paternal age and psychiatric illness in offspring remains to be further clarified. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Parental age and risk of epilepsy: A nationwide register‐based study

“…In this large population‐based cohort study, we found that parental age at the time of birth was associated with offspring risk of epilepsy, which is in line with recent findings from several other neuropsychiatric outcomes . In particular, we found that children born to mothers younger than 20 years and born to parental couples where paternal age exceeded maternal age by at least 5 years were at increased risk of developing epilepsy within the first 10 years of their life.…”

“…Advanced maternal age, conversely, has been suggested to increase offspring disease risk due to increased rates of genomic alterations, higher cumulative levels of harmful environmental exposures, and higher risk of perinatal and obstetric complications . Finally, prominent hypotheses linking advanced paternal age to offspring disease risk include increased frequency of de novo mutations in the male germline, age‐related epigenetic alterations, and selection into late fatherhood by factors associated with disease risk in the child (eg, mental illness) …”

“…17 Finally, prominent hypotheses linking advanced paternal age to offspring disease risk include increased frequency of de novo mutations in the male germline, age-related epigenetic alterations, and selection into late fatherhood by factors associated with disease risk in the child (eg, mental illness). 18 Despite the well-documented parental age effects in psychiatric disorders and the large overlap in the risk factors between psychiatric disorders and epilepsy, 19 little is known about how maternal and paternal age may affect the offspring's risk of epilepsy. A Danish study found increased risk of epilepsy in offspring born to fathers aged 35 years or older, 6 and in an early study published in 1946, epilepsy was reported to occur more frequently in offspring born to older mothers.…”

Widespread covariation of early environmental exposures and trait-associated polygenic variation

“…Harsh parental physical discipline such as hitting has been linked to increased emotional and behavioral problems including aggression in adolescence (10)(11)(12)(13)(14). Paternal age is a risk factor for a range of disorders and subclinical phenotypes including low academic achievement (15), with the link to autism spectrum disorders and schizophrenia most robustly replicated (16)(17)(18)(19)(20)(21). Breastfeeding and higher parental socioeconomic status (education, income, occupation) are protective factors for a range of outcomes including educational achievement (7,8,22).…”

The Age of the Father

“…A population registry-based study in the Netherlands found a significant association with increased paternal age for ASD, schizophrenia, and major depressive disorder, but not for bipolar disorder . Several hypotheses, including de novo mutations, epigenetic alterations, and selection into late fatherhood have been put forward to explain this paternal age effect [de Kluiver et al, 2017].…”