scholarly journals Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ditte Demontis ◽  
◽  
Raymond K. Walters ◽  
Veera M. Rajagopal ◽  
Irwin D. Waldman ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Disruptive Behavior ◽  
Attention Deficit ◽  
Behavior Disorders ◽  
Meta Analysis ◽  
Disruptive Behavior Disorders ◽  
Genetic Correlations ◽  
Chromosome 11 ◽  
Hyperactivity Disorder ◽  
Risk Variants

AbstractAttention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.

scholarly journals Identification of risk variants and characterization of the polygenic architecture of disruptive behavior disorders in the context of ADHD

2019 ◽  
Author(s):  
Ditte Demontis ◽  
Raymond Walters ◽  
Veera M. Rajagopal ◽  
Irwin D. Waldman ◽  
Jakob Grove ◽  
...  
Keyword(s):  
Disruptive Behavior ◽  
Behavior Disorders ◽  
Meta Analysis ◽  
Disruptive Behavior Disorders ◽  
Genetic Correlations ◽  
Polygenic Risk Score ◽  
Chromosome 11 ◽  
Risk Variants ◽  
Common Genetic Variants ◽  
Risk Locus

AbstractAttention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). ADHD comorbid with DBDs (ADHD+DBDs) is a complex phenotype with a risk component that can be attributed to common genetic variants. Here we report a large GWAS meta-analysis of ADHD+DBDs based on seven cohorts in total including 3,802 cases and 31,305 controls. Three genome-wide significant loci were identified on chromosomes 1, 7, and 11. A GWAS meta-analysis including a Chinese cohort supported the locus on chromosome 11 to be a strong risk locus for ADHD+DBDs across European and Chinese ancestries (rs7118422, P=3.15×10-10, OR=1.17). This locus was not associated with ADHD without DBDs in a secondary GWAS of 13,583 ADHD cases and 22,314 controls, suggesting that the locus is a specific risk locus for the comorbid phenotype.We found a higher SNP heritability for ADHD+DBDs (h2SNP =0.34) when compared to ADHD without DBDs (h2SNP =0.20). Genetic correlations of ADHD+DBDs with aggressive (rg =0.81) and anti-social behaviors (rg=0.82) were high, and polygenic risk score analyses revealed a significant increased burden of variants associated with ADHD and aggression in individuals with ADHD+DBDs compared to ADHD without DBDs. Our results suggests that ADHD+DBDs represent a more severe phenotype with respect to the genetic risk load than ADHD without DBDs, in line with previous studies, and that the risk load to some extent can be explained by variants associated with aggressive behavior.

scholarly journals Author Correction: Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ditte Demontis ◽  
◽  
Raymond K. Walters ◽  
Veera M. Rajagopal ◽  
Irwin D. Waldman ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Disruptive Behavior ◽  
Attention Deficit ◽  
Behavior Disorders ◽  
Disruptive Behavior Disorders ◽  
Hyperactivity Disorder ◽  
Risk Variants

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21566-w

Pharmacological Treatments for Attention-Deficit/Hyperactivity Disorder and Disruptive Behavior Disorders

2015 ◽  
Author(s):  
Erica Kass ◽  
Jonathan E. Posner ◽  
Laurence L. Greenhill
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Randomized Controlled Trials ◽  
Disruptive Behavior ◽  
Attention Deficit ◽  
Behavior Disorders ◽  
Disruptive Behavior Disorders ◽  
Controlled Trials ◽  
Type I ◽  
Hyperactivity Disorder ◽  
Randomized Controlled

More than 225 placebo-controlled type 1 investigations demonstrate that psychostimulants are highly effective in reducing core symptoms of attention-deficit/hyperactivity disorder (ADHD) in children and adults. In contrast, there are limited type I studies demonstrating that psychopharmacological management with U.S. Food & Drug Administration-approved agents for ADHD (stimulants and nonstimulants), atypical antipsychotics, and mood stabilizers decrease the defiant and aggressive behavior characteristic of disruptive behavior disorders. Stimulant treatment evidence has been supplemented by two large multisite randomized controlled trials. Randomized controlled trials from the past 15 years continue to report several key adverse events associated with stimulants but have not supported rarer and more serious problems. Although psychostimulants have been shown to retain their efficacy for as long as 14 months, their long-term academic and social benefits are not as robust. Nonstimulant agents for which there is more limited evidence of efficacy include atomoxetine, alpha-agonists, modafinil, and bupropion.

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