December 11, 2018
Younger siblings of children diagnosed with attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) are more likely to also be diagnosed with ASD or ADHD, according to a study published online December 10 in JAMA Pediatrics.
"These findings provide further support for shared familial mechanisms underlying ASD and ADHD, which may be useful for genetic and prospective developmental studies," write Meghan Miller, PhD, from the University of California, Davis, Health System, Sacramento, and colleagues.
Using patient data from two large healthcare systems, researchers evaluated recurrence risk and familial cross-aggregation among younger siblings of children with ASD (ASD risk, n = 158) or ADHD (ADHD risk, n = 730), compared with siblings of children with neither diagnosis (n = 14,287). The researchers included siblings aged 5 years or older who had a confirmed diagnosis.
The overall incidence of ASD and ADHD in this study population was 0.8% and 3.3%, respectively. However, the risk was not distributed evenly across the population.
Miller and colleagues found that the odds of an ASD diagnosis were approximately 30 times greater among siblings of children with ASD (odds ratio [OR], 30.38; 95% confidence interval [CI], 17.73 - 52.06) vs children with no-known-risk siblings. In addition, the risk for an ASD diagnosis was nearly seven times greater among siblings of children with ADHD (OR, 6.99; 95% CI, 3.42 - 14.27) vs those with no-known-risk siblings.
The researchers also found that the risk for an ADHD diagnosis was 13 times higher among children who had a sibling with ADHD than those with no known risk (OR, 13.05; 95% CI, 9.86 - 17.27). The risk for an ASD diagnosis was 3.5 times higher among children who had a sibling with ADHD (OR, 3.53; 95% CI, 1.57 - 7.94) compared with the no-known-risk siblings.
When factors such as sex, maternal age, or later-born sibling gestational age were included in the analysis, the odds of an ASD diagnosis were more than five times greater for boys than for girls (OR, 5.65, 95% CI, 3.24 - 9.85), and the odds of an ADHD diagnosis were more than twice as high for boys than for girls (OR, 2.6; 95% CI, 2.05 - 3.31).
The researchers acknowledge study limitations, including the lack of information on parental psychopathology, comorbidities, or birth complications, that could have affected outcomes.
"Etiologically, our findings of sibling cross-aggregation are consistent with partially shared genetic mechanisms underlying ASD and ADHD," write Miller and colleagues.
"Practitioners may wish to share such information with families given the potential relevance of monitoring social communication, attention, and behavior regulation skills in later-born siblings of children with ASD or ADHD," they conclude.
In an accompanying editorial, Tony Charman, PhD, and Emily J. H. Jones, PhD, from King's College London and the University of London, United Kingdom, write: "These within- and cross-condition recurrence figures are of important clinical usefulness in terms of informing discussions with parents about the need for enhanced developmental surveillance for neurodevelopmental conditions, such as ASD and ADHD, in their younger children."
Charman and Jones note, however, that the small sample size and wide confidence intervals may limit the clinical utility of the data and suggest that caution be used when conveying this information to parents.
"Although studies such as the present one will help to provide accessible and clinically translatable estimates of recurrence, more specialist training or even specialist genetic counseling services might have to be developed to provide this information to families sensitively and clearly in the way that is increasingly the case for monogenic forms of neurodevelopmental conditions," conclude the editorialists.
Funding for the study was provided in part by the National Institute of Mental Health. The study authors have disclosed no relevant financial relationships. Dr Charman receives research grant support from the Innovative Medicines Initiative, MQ, Autistica, the Charles Hawkins Fund, and the Waterloo Foundation. He has served as a paid consultant to F. Hoffmann-La Roche Ltd and receives royalties from Sage Publications and Guilford Publications. Dr Jones receives research grant support from the Innovative Medicines Initiative, MQ, Autistica, Action Medical Research, the Waterloo Foundation, and the Economic and Social Research Council.