Parental Age And Differential Risk For Asd, Adhd, Ocd And Tic Disorders: Data From A Large National Cohort

Abstract

Background Parental age is known to contribute to risk for various neurodevelopmental disorders, including autism spectrum disorder (ASD), schizophrenia, and intellectual disability. In this study we used a population-based cohort to assess the role of parental age in risk across childhood- and adolescent- onset neuropsychiatric disorders including ASD, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) and Tourette syndrome/chronic tic disorder (TS/CT). Methods Our study cohort included all singleton births, with age data on both parents (n=1,490,745), in Denmark between 1980 and 2007, followed through December 31, 2013. Cases of ASD, ADHD, OCD and TS/CT were identified in the Danish Psychiatric Central Register and the National Patient Register. Both the ADHD and ASD samples overlapped with those in recent reports, while the OCD and TS/CT samples had not been analyzed previously. Associations with parental age were modeled by a cubic spline with 4 knots in stratified Cox regression in which each birth year has its own baseline diagnostic rate while adjusting for the age of the opposite parent. Results Cases identified included 16,083 individuals diagnosed with ASD, 25,307 diagnosed with ADHD, 5,324 diagnosed with OCD and 4,666 individuals diagnosed with TS/CT. Younger maternal age was significantly associated with increased risk for ADHD (>1.4-fold increased risk, comparing point estimates of 25 yo mothers to the reference of 30 yo mothers), as well as with increased risk for ASD and for TS/CT. Moreover, association between maternal age and ASD risk followed a U-shaped curve, with increased risk associated with both younger and older mothers. Younger paternal age was also associated with significantly increased risk for ADHD. Advanced paternal age was associated with significantly increased risk for ASD (>1.2 fold at 40 yo), as well as ADHD. Discussion Parental age confers differential risk for different child- and adolescent- onset psychiatric disorders and the findings suggest a role for specific, known mechanisms in some of the disorders. Findings of advanced paternal age and risk for ASD and ADHD suggest a role for (1) de novo mutations and/or (2) epigenetic changes in both disorders. The association of younger maternal age with ASD, ADHD and TS/CT suggest that (3) maternal behaviors association with earlier parenting and/or (4) genetic factors that lead to both increased risk for these disorders and younger ages for child bearing are a part of the risk architecture for these disorders. Our results are consistent with a model of distinct and overlapping risk architecture for child- and adolescent- onset neuropsychiatric disease.