BACKGROUND: We reviewed systematically the results of genetic studies investigating associations between putative susceptibility genes for attention-deficit hyperactivity disorder (ADHD) and neuropsychological traits relevant for this disorder. METHODS: We identified papers for review through the PubMed database. RESULTS: Twenty-nine studies examined 10 genes (DRD4, DAT1, COMT, DBH, MAOA, DRD5, ADRA2A, GRIN2A, BDNF and TPH2) in relation to neuropsychological traits relevant for ADHD. For DRD4, the continuous performance test (CPT) and derived tasks were the most used tests. Association of high reaction time variability with the 7-repeat allele absence appears to be the most consistent result and seems to be specific to ADHD. Speed of processing, set-shifting and cognitive impulsiveness were less frequently investigated but seem to be altered in the 7-repeat allele carriers. No effect of genotype was found on response inhibition (the stop and go/no-go tasks). For DAT1, 4 studies provide conflicting results in relation to omission and commission errors from CPT and derived tasks. High reaction time variability seems to be the most replicated cognitive marker associated with the 10-repeat homozygosity. The other genes have attracted fewer studies, and the reported findings need to be replicated. LIMITATIONS: Although we aimed to perform a formal meta-analysis, this was not possible because the number of studies using the same neurocognitive endophenotypes was limited. We referred only minimally to the various theoretical frameworks in this field of research; more detail would have been beyond the scope of our systematic review. Finally, sample sizes in most of the studies we reviewed were small. Thus, some negative findings could be attributed to a lack of statistical power, and positive results should be considered preliminary until they are replicated in extended samples. CONCLUSION: Several methodological issues, including measurement errors, developmental changes in cognitive abilities, sex, psychostimulant effects and presence of comorbid conditions, represent confounding factors and may explain conflicting results.
BACKGROUND: We reviewed systematically the results of genetic studies investigating associations between putative susceptibility genes for attention-deficit hyperactivity disorder (ADHD) and neuropsychological traits relevant for this disorder. METHODS: We identified papers for review through the PubMed database. RESULTS: Twenty-nine studies examined 10 genes (DRD4, DAT1, COMT, DBH, MAOA, DRD5, ADRA2A, GRIN2A, BDNF and TPH2) in relation to neuropsychological traits relevant for ADHD. For DRD4, the continuous performance test (CPT) and derived tasks were the most used tests. Association of high reaction time variability with the 7-repeat allele absence appears to be the most consistent result and seems to be specific to ADHD. Speed of processing, set-shifting and cognitive impulsiveness were less frequently investigated but seem to be altered in the 7-repeat allele carriers. No effect of genotype was found on response inhibition (the stop and go/no-go tasks). For DAT1, 4 studies provide conflicting results in relation to omission and commission errors from CPT and derived tasks. High reaction time variability seems to be the most replicated cognitive marker associated with the 10-repeat homozygosity. The other genes have attracted fewer studies, and the reported findings need to be replicated. LIMITATIONS: Although we aimed to perform a formal meta-analysis, this was not possible because the number of studies using the same neurocognitive endophenotypes was limited. We referred only minimally to the various theoretical frameworks in this field of research; more detail would have been beyond the scope of our systematic review. Finally, sample sizes in most of the studies we reviewed were small. Thus, some negative findings could be attributed to a lack of statistical power, and positive results should be considered preliminary until they are replicated in extended samples. CONCLUSION: Several methodological issues, including measurement errors, developmental changes in cognitive abilities, sex, psychostimulant effects and presence of comorbid conditions, represent confounding factors and may explain conflicting results.
Authors: Robert F Asarnow; Keith H Nuechterlein; Kenneth L Subotnik; David L Fogelson; Richard D Torquato; Diana L Payne; Joy Asamen; Jim Mintz; Donald Guthrie Journal: Arch Gen Psychiatry Date: 2002-11
Authors: B G Schimmelmann; S Friedel; A Dempfle; A Warnke; K P Lesch; S Walitza; T J Renner; M Romanos; B Herpertz-Dahlmann; M Linder; H Schäfer; C Seitz; H Palmason; C Freitag; J Meyer; K Konrad; A Hinney; J Hebebrand Journal: J Neural Transm (Vienna) Date: 2007-01-15 Impact factor: 3.575
Authors: Alysa E Doyle; Erik G Willcutt; Larry J Seidman; Joseph Biederman; Virginie-Anne Chouinard; Julie Silva; Stephen V Faraone Journal: Biol Psychiatry Date: 2005-06-01 Impact factor: 13.382
Authors: Mark A Bellgrove; Ziarih Hawi; Aiveen Kirley; Michael Fitzgerald; Michael Gill; Ian H Robertson Journal: Neuropsychopharmacology Date: 2005-12 Impact factor: 7.853
Authors: Penny Andreou; Ben M Neale; Wai Chen; Hanna Christiansen; Isabel Gabriels; Alexander Heise; Sheera Meidad; Ueli C Muller; Henrik Uebel; Tobias Banaschewski; Iris Manor; Robert Oades; Herbert Roeyers; Aribert Rothenberger; Pak Sham; Hans-Christoph Steinhausen; Philip Asherson; Jonna Kuntsi Journal: Psychol Med Date: 2007-05-31 Impact factor: 7.723
Authors: Benjamin M Neale; Sarah Medland; Stephan Ripke; Richard J L Anney; Philip Asherson; Jan Buitelaar; Barbara Franke; Michael Gill; Lindsey Kent; Peter Holmans; Frank Middleton; Anita Thapar; Klaus-Peter Lesch; Stephen V Faraone; Mark Daly; Thuy Trang Nguyen; Helmut Schäfer; Hans-Christoph Steinhausen; Andreas Reif; Tobias J Renner; Marcel Romanos; Jasmin Romanos; Andreas Warnke; Susanne Walitza; Christine Freitag; Jobst Meyer; Haukur Palmason; Aribert Rothenberger; Ziarih Hawi; Joseph Sergeant; Herbert Roeyers; Eric Mick; Joseph Biederman Journal: J Am Acad Child Adolesc Psychiatry Date: 2010-08-05 Impact factor: 8.829
Authors: Viviana A Peskin; Anna Ordóñez; R Scott Mackin; Kevin Delucchi; Silvia Monge; James J McGough; Denise A Chavira; Monica Berrocal; Erika Cheung; Eduardo Fournier; Judith A Badner; Luis Diego Herrera; Carol A Mathews Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2015-03-31 Impact factor: 3.568
Authors: Maggie M Sweitzer; Indrani Halder; Janine D Flory; Anna E Craig; Peter J Gianaros; Robert E Ferrell; Stephen B Manuck Journal: Soc Cogn Affect Neurosci Date: 2012-02-15 Impact factor: 3.436
Authors: L Cinnamon Bidwell; Joshua C Gray; Jessica Weafer; Abraham A Palmer; Harriet de Wit; James MacKillop Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2017-06 Impact factor: 3.568