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Tuesday, January 28, 2014

Paternal Age and Psychiatric Disorders

At JAMA Psychiatry, John J. McGrath and colleagues have an article titled  "A Comprehensive Assessment of Parental Age and Psychiatric Disorders."
Importance There has been recent interest in the findings that the offspring of older fathers have an increased risk of both de novo mutations and neuropsychiatric disorders. However, the offspring of younger parents are also at risk for some adverse mental health outcomes.
Objective To determine the association between maternal and paternal age and a comprehensive range of mental health disorders.
Design, Setting, and Participants A comprehensive, population-based record linkage study using the Danish Psychiatric Central Research Register from January 1, 1995, through December 31, 2011. A total of 2 894 688 persons born in Denmark from January 1, 1955, through December 31, 2006, were followed up during the study period.
Exposures Maternal and paternal age at the time of offspring’s birth.
Main Outcomes and Measures We examined a broad range of International Classification of Diseases–defined mental disorders, including substance use; schizophrenia and related disorders; mood disorders; neurotic, stress-related, and somatoform disorders; eating disorders; specific personality disorders; and a range of developmental and childhood disorders. The incidence rate ratios for each mental disorder outcome were estimated by log linear Poisson regression with adjustments for the calendar period, age, sex, and age of the other parent.
Results The cohort was observed for 42.7 million person-years, during which 218 441 members of the cohort had their first psychiatric contact for any psychiatric disorder. Based on the overall risk of psychiatric disorders, the offspring of younger and older parents were at increased risk compared with those of parents aged 25 to 29 years. When the offspring were examined for particular disorders, the nature of the relationship changed. For example, the offspring of older fathers were at an increased risk of schizophrenia and related disorders, mental retardation, and autism spectrum disorders. In contrast, the offspring of young mothers (and to a lesser extent young fathers) were at an increased risk for substance use disorders, hyperkinetic disorders, and mental retardation.
Conclusions and Relevance The offspring of younger mothers and older fathers are at risk for different mental health disorders. These differences can provide clues to the complex risk architecture underpinning the association between parental age and the mental health of offspring.

Systematic reviews and meta-analyses have provided strong evidence indicating that the offspring of older fathers have an increased risk for schizophrenia1 and autism.2 Malaspina and colleagues3proposed that age-related de novo mutations in the male germline may contribute to an increased risk for neurodevelopmental disorders. In recent years, a growing body of data from genetic studies4- 7 has lent weight to this hypothesis. Apart from schizophrenia and autism, evidence suggests that the offspring of older fathers have an increased risk for bipolar disorder.8 Age-related mutagenesis in the male germline may also contribute to an increased risk for schizophrenia and autism in grandchildren,9,10 suggesting that some mutations may be silent (ie, with lower penetrance) in the first-generation offspring but still contribute to disease risk in subsequent generations. [emphasis added]