Familiality and molecular genetics of attention networks in ADHD.
Indices from a more elementary neuropsychological level might be useful in the search for genes for complex psychiatric disorders, such as ADHD. In this study we investigated systematically whether attentional performance as measured with the Attention Network Test (ANT) is suited for the identification of endophenotypes of ADHD. Attentional performance in affected sib pairs with ADHD (n = 181) was compared to unaffected control siblings (n = 121). Intrafamilial correlation patterns were calculated. In addition, linkage and association analyses were conducted between quantitative scores of attentional functions and dopamine receptor D4 (DRD4) and dopamine transporter (DAT1 or SLC6A3) gene variants. Only the executive attention network was significantly impaired in subjects with ADHD compared to controls (P < 0.05) and showed evidence for familiality in both affected and unaffected families. Linkage analyses revealed the highest LOD score for a severity score based on DSM-IV inattentive symptoms in the DAT1 chromosomal region (LOD score 2.6 at 15 cM). However, a SNP (rs6350) at the DAT1 locus showed a tendency for association with both alerting performance (P = 0.02) and executive attention (P = 0.01) although it did not survive alpha adjustment for multiple testing. No evidence was found for association of any of the investigated phenotypes with the VNTR in the DRD4. Thus, our data suggest that the quantitative behavioral ratings of inattentive symptoms might be more useful when searching for new genes associated with ADHD, however, among the ANT measures the executive attention network seems to be best suited for further endophenotype analyses.
Child Neuropsychology Section, Department of Child and Adolescent Psychiatry of RTWH Aachen, Aachen, Germany. kkonrad@ukaachen.de
Kerstin
K
Konrad
Astrid
A
Dempfle
Susann
S
Friedel
Philip
P
Heiser
Kristian
K
Holtkamp
Susanne
S
Walitza
Sascha
S
Sauer
Andreas
A
Warnke
Helmut
H
Remschmidt
Susanne
S
Gilsbach
Helmut
H
Schäfer
Anke
A
Hinney
Johannes
J
Hebebrand
Beate
B
Herpertz-Dahlmann
D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human