Abstract
It is unknown why attention deficit hyperactivity disorder (ADHD) is more common in males, whereas anxiety and depression show a female population excess. We tested the hypothesis that anxiety and depression risk alleles manifest as ADHD in males. We also tested whether anxiety and depression in children with ADHD show a different etiology to typical anxiety and depression and whether this differs by sex. The primary clinical ADHD sample consisted of 885 (14% female) children. Psychiatric symptoms were assessed using standardized interviews. Polygenic risk scores (PRS) were derived using large genetic studies. Replication samples included independent clinical ADHD samples (N=3,794; 25.7% female) and broadly defined population ADHD samples (N=995; 33.4% female). We did not identify sex differences in anxiety or depression PRS in children with ADHD. In the primary sample, anxiety PRS were associated with social and generalized anxiety in males, with evidence of a sex-by-PRS interaction for social anxiety. These results did not replicate in the broadly defined ADHD sample. Depression PRS were not associated with comorbid depression symptoms. The results suggest that anxiety and depression genetic risks are not more likely to lead to ADHD in males. Also, the evidence for shared etiology between anxiety symptoms in those with ADHD and typical anxiety was weak and needs replication.
Highlights
The members of the Psychiatric Genomics Consortium ADHD Working Group are provided in the Appendix.Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder (Thapar, 2018)
In the primary ADHD sample, we found that anxiety Polygenic risk scores (PRS) were associated with presence of generalized anxiety disorder (GAD) [OR(CIs) = 1.38(1.09–1.76), p = .0082, R2 = 0.017] and social anxiety symptoms [OR(CIs) = 1.38(1.06–1.81), p = .017, R2 = 0.017], though the latter association results did not survive correction for multiple testing; see Figure and Table S2 for detailed results
The results did not support our hypothesis of a higher polygenic burden for anxiety and depression in males with ADHD compared with affected females
Summary
Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder (Thapar, 2018). Neurodevelopmental disorders, including ADHD and autism spectrum. Disorder (ASD), are typified by a male excess in prevalence (Thapar, Cooper, & Rutter, 2017). ADHD is 2–7 times more frequently diagnosed in males than females, though by adulthood the rate is similar in males and females (Franke et al, 2018). The male excess in ADHD prevalence in childhood is especially prominent in clinically ascertained samples but it is present in community samples (Faraone et al, 2015). The reasons why ADHD is more common in males in childhood are not yet known (Rutter, Caspi, & Moffitt, 2003)
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