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Am J Med Genet B Neuropsychiatr Genet. 2015 Sep;168(6):471-479. doi: 10.1002/ajmg.b.32290. Epub 2015 Jan 14.

The role of age in association analyses of ADHD and related neurocognitive functioning: A proof of concept for dopaminergic and serotonergic genes.

Author information

1
Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
2
Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
3
Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.
4
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud university medical center, Nijmegen, The Netherlands.
5
King's College London, Institute of Psychiatry, United Kingdom.
6
Department of Psychology, VU University, Amsterdam, The Netherlands.
7
Department of Psychiatry, University Medical Centre Groningen, University of Groningen, The Netherlands.

Abstract

Elucidating genetic mechanisms involved in Attention-Deficit/Hyperactivity Disorder (ADHD) has been challenging. Relatively unexplored is the fact that genetic mechanisms can differ with age. The current study explored the association between dopaminergic and serotonergic genes, ADHD symptoms, and neurocognitive functioning in relation to age. Associations of three genetic ADHD risk factors, DAT1, DRD4, and 5-HTT with symptoms and six neurocognitive measures were explored in two samples of the NeuroIMAGE study: 756 children, adolescents, and young adults with ADHD, their siblings, and controls (M age 17 years, SD 3.2), and 393 parents with and without ADHD (M age 48 years, SD 4.8). Association analyses were performed in both samples, and effects were compared to address dichotomous age effects. Gene*age interactions were examined to address continuous age effects. Moderating effects of age were found for DRD4-7R carriership and ADHD symptoms in the adult group only; in the adolescents the 5-HTT LL genotype was differentially associated with inhibition and with motor timing at different ages, and to inhibition in adults; DAT1 10-6 haplotype carriership showed differential working memory performance depending on age. None of our effects survived correction for multiple comparisons. Our results are preliminary, but may point to differential genotype-phenotype associations at different ages. This can be seen as a proof of concept for the importance of age in dopaminergic and serotonergic genetic association analyses. Our findings are consistent with the idea that genetic and neurocognitive mechanisms underlying ADHD may change throughout life.

KEYWORDS:

ADHD; age; dopamine; neuropsychology; serotonin

PMID:
25586935
DOI:
10.1002/ajmg.b.32290

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