An exploratory study of the relationship between four candidate genes and neurocognitive performance in adult ADHD

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 147B; no. 3; pp. 397 - 402
• Main Authors: Boonstra, A. Marije, Kooij, J.J. Sandra, Buitelaar, Jan K., Oosterlaan, Jaap, Sergeant, Joseph A., Heister, J.G.A.M. Angelien, Franke, Barbara
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 05.04.2008; Wiley-Liss
• Subjects: Adult; Attention Deficit Disorder with Hyperactivity - genetics; Attention Deficit Disorder with Hyperactivity - psychology; attention deficit hyperactivity disorder; Base Sequence; Biological and medical sciences; Cognition; DNA Primers; endophenotype; executive functions; Female; genetics; Humans; Male; Medical genetics; Medical sciences; Middle Aged; neuropsychological testing; Polymorphism, Genetic; Human; Performance evaluation; Executive function; attention deficit hyperactivity disorder; Hyperactivity; Pathogenesis; endophenotype; Genetic determinism; neuropsychological testing; Attentional disorder; executive functions; Adult; Genetics; Attention disorder with hyperactivity; Performance
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30595

Since neurocognitive performance is a possible endophenotype for Attention Deficit Hyperactivity Disorder (ADHD) we explored the relationship between four genetic polymorphisms and neurocognitive performance in adults with ADHD. We genotyped a sample of 45 adults with ADHD at four candidate polymorphisms for the disorder (DRD4 48 base pair (bp) repeat, DRD4 120 bp duplicated repeat, SLC6A3 (DAT1) 40 bp variable number of tandem repeats (VNTR), and COMT Val158Met). We then sub‐grouped the sample for each polymorphism by genotype or by the presence of the (putative) ADHD risk allele and compared the performance of the subgroups on a large battery of neurocognitive tests. The COMT Val158Met polymorphism was related to differences in IQ and reaction time, both of the DRD4 polymorphisms (48 bp repeat and 120 bp duplication) showed an association with verbal memory skills, and the SLC6A3 40 bp VNTR polymorphism could be linked to differences in inhibition. Interestingly, the presence of the risk alleles in DRD4 and SLC6A3 was related to better cognitive performance. Our findings contribute to an improved understanding of the functional implications of risk genes for ADHD. © 2007 Wiley‐Liss, Inc.