Response Inhibition and ADHD Traits: Correlates and Heritability in a Community Sample

Crosbie, Jennifer; Arnold, Paul; Paterson, Andrew D.; Swanson, James M.; Dupuis, Annie; Li, X.; Shan, Janet; Goodale, Tara; Tam, Celia; Strug, Lisa J.; Schachar, Russell · 2013 · OpenAlex-citations

DOI: 10.1007/s10802-012-9693-9

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Summary

This study investigates whether response inhibition, response latency, and response variability serve as valid endophenotypes for Attention Deficit Hyperactivity Disorder (ADHD). Endophenotypes are intermediate biological traits that mediate the link between genetic risk and clinical disorder, potentially simplifying genetic discovery by reducing phenotypic heterogeneity. The authors aimed to determine if these cognitive measures, derived from the Stop Signal Task (SST), are correlated with ADHD traits in the general population, heritable, and share genetic risk with ADHD symptoms. The research utilized a large community sample of 16,099 children and adolescents (ages 6–18) recruited from the Ontario Science Centre. ADHD traits were measured using the Strengths and Weaknesses of ADHD-symptoms and Normal-Behavior (SWAN) rating scale. Cognitive performance was assessed via the SST, yielding three primary metrics: Stop Signal Reaction Time (SSRT) for inhibition, Go Reaction Time (GoRT) for latency, and Go Reaction Time Standard Deviation (GoRTSD) for variability. After excluding participants with invalid performance or recent medication use, the final analysis included 14,388 individuals. Heritability and shared genetic risk were estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR) on a subset of 7,483 siblings from 3,507 families. Regression analyses controlled for age, sex, ethnicity, socioeconomic status, and family structure. The results demonstrated that individuals with higher ADHD trait scores exhibited significantly worse response inhibition (longer SSRT), slower response latency (longer GoRT), and greater response variability (higher GoRTSD). These effects were consistent across age and gender, though gender differences were more pronounced in younger participants. All three cognitive measures and ADHD traits (total, inattention, and hyperactivity-impulsivity) were significantly heritable. Crucially, bivariate heritability analyses revealed a significant genetic correlation between ADHD traits and response inhibition (SSRT), indicating shared genetic risk. However, no significant genetic correlation was found between ADHD traits and response latency or variability, despite their phenotypic association with ADHD. Inattention and hyperactivity-impulsivity subscores showed complete pleiotropy. The study concludes that response inhibition is a valid endophenotype for ADHD, as it is associated with the disorder, heritable, and shares genetic risk with ADHD traits. In contrast, response latency and variability, while heritable and phenotypically linked to ADHD, do not share genetic risk and thus do not meet the criteria for endophenotypes in this context. These findings support the use of response inhibition as a tool for genetic studies of ADHD, potentially aiding in the identification of risk genes by focusing on a biologically specific trait rather than the complex clinical diagnosis.

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• cognitive capacity variation