Working memory and reaction time variability mediate the relationship between polygenic risk and ADHD traits in a general population sample

Abstract

Endophenotypes are heritable and quantifiable traits indexing genetic liability for a disorder. Here, we examined three potential endophenotypes, working memory function, response inhibition, and reaction time variability, for attention-deficit hyperactivity disorder (ADHD) measured as a dimensional latent trait in a large general population sample derived from the Adolescent Brain Cognitive DevelopmentSM Study. The genetic risk for ADHD was estimated using polygenic risk scores (PRS) whereas ADHD traits were quantified as a dimensional continuum using Bartlett factor score estimates, derived from Attention Problems items from the Child Behaviour Checklist and Effortful Control items from the Early Adolescent Temperament Questionnaire-Revised. The three candidate cognitive endophenotypes were quantified using task-based performance measures. Higher ADHD PRSs were associated with higher ADHD traits, as well as poorer working memory performance and increased reaction time variability. Lower working memory performance, poorer response inhibition, and increased reaction time variability were associated with more pronounced ADHD traits. Working memory and reaction time variability partially statistically mediated the relationship between ADHD PRS and ADHD traits, explaining 14% and 16% of the association, respectively. The mediation effect was specific to the genetic risk for ADHD and did not generalise to genetic risk for four other major psychiatric disorders. Together, these findings provide robust evidence from a large general population sample that working memory and reaction time variability can be considered endophenotypes for ADHD that mediate the relationship between ADHD PRS and ADHD traits.

Central executive training for ADHD: Impact on organizational skills at home and school. A randomized controlled trial.

“…These results were generally consistent with crosssectional work, demonstrating that working memory difficulties predict organizational problems even when controlling for ADHD symptoms (Kofler, Sarver, Harmon, et al, 2018). Collectively, these findings contribute to the quickly growing evidence base linking working memory with ADHD behavioral symptoms (e.g., Kofler et al, 2011;Raiker et al, 2012;Rapport et al, 2009), functional impairments (e.g., Kofler et al, 2011;Singh et al, 2022), and genetic risk for ADHD (Moses et al, 2022).…”

Distinct mechanisms of attentional suppression: exploration of trait factors underlying cued- and learned-suppression

“…Interestingly, our recent study also revealed that individuals with higher proactive control, characterized by lower SD-RT, experienced greater benefits from negative cues (Chidharom & Carlisle, under review). The current results suggest that individuals with lower SD-RT demonstrate higher working memory capacity (Buzy et al, 2009 ; Kofler et al, 2014 ; Moses et al, 2022 ), enabling them to effectively engage proactive control to suppress cued distractors. Overall, our findings highlight the critical role of VWM capacities in efficiently utilizing negative cues and suggest that individuals with higher working memory capacity demonstrate enhanced engagement of proactive control to suppress distractors.…”

Protocol and preregistration for the CODEC project: Measuring, modelling and mechanistically understanding the nature of cognitive variability in early childhood

“…In light of these ndings, the socio-economic environment of a family could impact a child's cognitive variability. Beyond these familial environments, hereditary factors might further (at least in part) explain variability (Moses et al, 2022). For this reason, a subset of parents will perform the same cognitive tasks as their children, allowing us to quantify the within-family similarities above and beyond other factors.…”