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The influence of serotonin- and other genes on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder (ADHD) : findings from a family-based association test (FBAT) analysis

Oades, Robert D. and Lasky-Su, Jessica and Christiansen, Hanna and Faraone, Stephen V. and Sonuga-Barke, Edmund Js and Banaschewski, Tobias and Chen, Wai and Anney, Richard Jl and Buitelaar, Jan K. and Ebstein, Richard P. and Franke, Barbara and Gill, Michael and Miranda, Ana and Roeyers, Herbert and Rothenberger, Aribert and Sergeant, Joseph A. and Steinhausen, Hans-Christoph and Taylor, Eric A. and Thompson, Margaret and Asherson, Philip. (2008) The influence of serotonin- and other genes on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder (ADHD) : findings from a family-based association test (FBAT) analysis. Behavioral and brain functions, Vol. 4 , no. 48.

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Official URL: http://edoc.unibas.ch/dok/A5250664

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Abstract

ABSTRACT: BACKGROUND: Low serotonergic (5-HT) activity correlates with increased impulsive-aggressive behavior, while the opposite association may apply to cognitive impulsiveness. Both types of impulsivity are associated with attention-deficit/hyperactivity disorder (ADHD), and genes of functional significance for the 5-HT system are implicated in this disorder. Here we demonstrate the separation of aggressive and cognitive components of impulsivity from symptom ratings and test their association with 5-HT and functionally related genes using a family-based association test (FBAT-PC). METHODS: Our sample consisted of 1180 offspring from 607 families from the International Multicenter ADHD Genetics (IMAGE) study. Impulsive symptoms were assessed using the long forms of the Conners and the Strengths and Difficulties parent and teacher questionnaires. Factor analysis showed that the symptoms aggregated into parent- and teacher-rated behavioral and cognitive impulsivity. We then selected 582 single nucleotide polymorphisms (SNPs) from 14 genes directly or indirectly related to 5-HT function. Associations between these SNPs and the behavioral/cognitive groupings of impulsive symptoms were evaluated using the FBAT-PC approach. RESULTS: In the FBAT-PC analysis for cognitive impulsivity 2 SNPs from the gene encoding phenylethanolamine N-methyltransferase (PNMT, the rate-limiting enzyme for adrenalin synthesis) attained corrected gene-wide significance. Nominal significance was shown for 12 SNPs from BDNF, DRD1, HTR1E, HTR2A, HTR3B, DAT1/SLC6A3, and TPH2 genes replicating reported associations with ADHD. For overt aggressive impulsivity nominal significance was shown for 6 SNPs from BDNF, DRD4, HTR1E, PNMT, and TPH2 genes that have also been reported to be associated with ADHD. Associations for cognitive impulsivity with a SERT/SLC6A4 variant (STin2: 12 repeats) and aggressive behavioral impulsivity with a DRD4 variant (exon 3: 3 repeats) are also described. DISCUSSION: A genetic influence on monoaminergic involvement in impulsivity shown by children with ADHD was found. There were trends for separate and overlapping influences on impulsive-aggressive behavior and cognitive impulsivity, where an association with PNMT (and arousal mechanisms affected by its activity) was more clearly involved in the latter. Serotonergic and dopaminergic mechanisms were implicated in both forms of impulsivity with a wider range of serotonergic mechanisms (each with a small effect) potentially influencing cognitive impulsivity. These preliminary results should be followed up with an examination of environmental influences and associations with performance on tests of impulsivity in the laboratory.
Faculties and Departments:07 Faculty of Psychology > Departement Psychologie > Ehemalige Einheiten Psychologie > Clinical Child and Adolescent Psychology (Schneider)
UniBasel Contributors:Steinhausen, Hans-Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:BioMed Central
ISSN:1744-9081
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Jun 2012 06:44
Deposited On:22 Mar 2012 13:47

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