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A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).
The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.
When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).
We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.
Attention-deficit/hyperactivity disorder (ADHD) often persists into adolescence and adulthood, but the processes underlying persistence and remission remain poorly understood. We previously found that reaction time variability and event-related potentials of preparation-vigilance processes were impaired in ADHD persisters and represented markers of remission, as ADHD remitters were indistinguishable from controls but differed from persisters. Here, we aimed to further clarify the nature of the cognitive-neurophysiological impairments in ADHD and of markers of remission by examining the finer-grained ex-Gaussian reaction-time distribution and electroencephalographic (EEG) brain-oscillatory measures in ADHD persisters, remitters and controls.
A total of 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 age-matched controls were compared on ex-Gaussian (mu, sigma, tau) indices and time-frequency EEG measures of power and phase consistency from a reaction-time task with slow-unrewarded baseline and fast-incentive conditions (‘Fast task’).
Compared to controls, ADHD persisters showed significantly greater mu, sigma, tau, and lower theta power and phase consistency across conditions. Relative to ADHD persisters, remitters showed significantly lower tau and theta power and phase consistency across conditions, as well as lower mu in the fast-incentive condition, with no difference in the baseline condition. Remitters did not significantly differ from controls on any measure.
We found widespread impairments in ADHD persisters in reaction-time distribution and brain-oscillatory measures. Event-related theta power, theta phase consistency and tau across conditions, as well as mu in the more engaging fast-incentive condition, emerged as novel markers of ADHD remission, potentially representing compensatory mechanisms in individuals with remitted ADHD.
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