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

Kamradt, Jaclyn M.; Nigg, Joel T.; Friderici, Karen H.; Nikolas, Molly A.

doi:10.1017/s0954579416000195

Cited by 19Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

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

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Kamradt, Jaclyn M., Nigg, Joel T., Friderici, Karen H., Nikolas, Molly A.·2017·Development and Psychopathology

DOI 10.1017/s0954579416000195PMC PMC5053856

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Abstract

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.

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Kamradt reported, in a different sample using a candidate gene approach, that response inhibition mediated the effect of polymorphisms at DRD4 and DAT1.
“Kamradt34 reported in a different sample using a candidate gene approach that response inhibition mediated the effect of polymorphisms at DRD4 and DAT1.”
From Working Memory and Vigilance as Multivariate Endophenotypes Related to Common Genetic Risk for Attention-Deficit/Hyperactivity Disorder (2018) · cites this paper as [34]

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BackgroundInfluential
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Working Memory and Vigilance as Multivariate Endophenotypes Related to Common Genetic Risk for Attention-Deficit/Hyperactivity Disorder
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Authors: Kamradt, J. M., Nigg, J. T., Friderici, K. H., & Nikolas, M. A.
Affiliations: University of Iowa (US)
Oregon Health & Science University (US)
Michigan State University (US)
Corresponding author: Kamradt, Jaclyn M.
ORCID: Kamradt, Jaclyn M.
Nigg, Joel T.
Friderici, Karen H.
Nikolas, Molly A.
Venue: Development and Psychopathology
Publisher: Cambridge University Press (CUP)
Published: 2016-04-06
Volume: 29
Issue: 1
Pages: 259-272
ISSN: 0954-5794 (ISSN-L)
1469-2198
DOI: 10.1017/s0954579416000195
PMC: PMC5053856
OpenAlex: W2328930478
Cited by: 19
References: 95
Citations by year: 2026: 1 · 2025: 1 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 1
FWCI: 2.96
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.cambridge.org/core/terms (unspecified)
Locations: Development and Psychopathology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (5r01mh099064-05)
National Institute of Mental Health (R01-MH099064, R01MH070004, R37MH059105)
National Institute of General Medical Sciences (T32GM108540)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: attention deficit hyperactivity disorder, endophenotypes, neuropsychological performance, response inhibition, dopamine transporter gene, DAT1, DRD4, dopamine D4 receptor, genetic polymorphism, inattention, hyperactivity/impulsivity, oppositionality, externalizing problems, youth
MeSH terms: Adolescent, Alleles, Attention, Attention Deficit Disorder with Hyperactivity, Child, Cognition, Dopamine, Female, Genotype, Humans, Impulsive Behavior, Male, Phenotype, Polymorphism, Genetic, Promoter Regions, Genetic, Dopamine Plasma Membrane Transport Proteins, Receptors, Dopamine D4, Executive Function, Genetic Association Studies

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

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