Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-6507

Oades, R D; Lasky-Su, J; Christiansen, H; Faraone, S V; Sonuga-Barke, E J; Banaschewski, T; Chen, W; Anney, R J L; Buitelaar, J K; Ebstein, R P; Franke, B; Gill, M; Miranda, A; Roeyers, H; Rothenberger, A; Sergeant, J A; Steinhausen, H C; Taylor, E A; Thompson, M; Asherson, P (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, 4:48:1-14.

[img]
Preview
PDF
1MB

View at publisher

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.

Citations

58 citations in Web of Science®
61 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

246 downloads since deposited on 09 Jan 2009
116 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
DDC:610 Medicine & health
Language:English
Date:20 October 2008
Deposited On:09 Jan 2009 10:13
Last Modified:27 Nov 2013 23:53
Publisher:BioMed Central
ISSN:1744-9081
Additional Information:Free full text article
Publisher DOI:10.1186/1744-9081-4-48
PubMed ID:18937842

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page