Neuropsychological performance measures as intermediate phenotypes for attention-deficit/hyperactivity disorder: A multiple mediation analysis

• Published in: Development and psychopathology Vol. 29; no. 1; p. 259
• Main Authors: Kamradt, Jaclyn M, Nigg, Joel T, Friderici, Karen H, Nikolas, Molly A
• Format: Journal Article
• Language: English
• Published: United States 01-02-2017
• Subjects: Adolescent; Alleles; Attention - physiology; Attention Deficit Disorder with Hyperactivity - genetics; Attention Deficit Disorder with Hyperactivity - psychology; Child; Cognition - physiology; Dopamine; Dopamine Plasma Membrane Transport Proteins - genetics; Executive Function - physiology; Female; Genetic Association Studies; Genotype; Humans; Impulsive Behavior - physiology; Male; Phenotype; Polymorphism, Genetic; Promoter Regions, Genetic; Receptors, Dopamine D4 - genetics
• ISSN: 1469-2198
• DOI: 10.1017/S0954579416000195

Genetic influences on dopaminergic neurotransmission have been implicated in attention-deficit hyperactivity disorder (ADHD) and are theorized to impact cognitive functioning via alterations in frontal-striatal circuitry. Neuropsychological functioning has been proposed to account for the potential associations between dopamine candidate genes and ADHD. However, to date, this mediation hypothesis has not been directly tested. Participants were 498 youth ages 6-17 years (mean M = 10.8 years, SD = 2.4 years, 55.0% male). All youth completed a multistage, multiple-informant assessment procedure to identify ADHD and non-ADHD cases, as well as a comprehensive neuropsychological battery. Youth provided a saliva sample for DNA analyses; the 480 base pair variable number of tandem repeat polymorphism of the dopamine active transporter 1 gene (DAT1) and the 120 base pair promoter polymorphism of the dopamine receptor D4 gene (DRD4) were genotyped. Multiple mediation analysis revealed significant indirect associations between DAT1 genotype and inattention, hyperactivity-impulsivity, and oppositionality, with specific indirect effects through response inhibition. The results highlight the role of neurocognitive task performance, particularly response inhibition, as a potential intermediate phenotype for ADHD, further elucidating the relationship between genetic polymorphisms and externalizing psychopathology.