Molecular genetic contribution to the developmental course of attention-deficit hyperactivity disorder.
OBJECTIVE
The developmental trajectory of attention-deficit hyperactivity disorder (ADHD) is variable. Utilizing a longitudinally assessed sample, we investigated the contribution of susceptibility gene variants, previously implicated through pooled or meta-analyses, to the developmental course of Attention-Deficit Hyperactivity Disorder over time.


METHODS
151 children (aged 6-12) who met diagnostic criteria for ADHD were assessed using research diagnostic interviews during childhood and 5 years later in adolescence. Severity was defined as total number of ADHD symptoms at baseline and reassessment. Association with variants at DRD4, DRD5, and the dopamine transporter gene, DAT was analyzed using linear regression.


RESULTS
As expected, affected individuals showed a decline in ADHD severity over time. The DRD4 48 bp VNTR 7-repeat and DRD5 CA(n) microsatellite marker 148 bp risk alleles were associated with persistent ADHD. Those possessing the DRD4 7 repeat risk allele showed less of a decline in severity at reassessment than those without the risk allele.


CONCLUSIONS
Those carrying the DRD4 7 risk allele showed greater symptom severity at follow-up and less ADHD reduction over time. These findings support the hypothesis that some susceptibility genes for ADHD also influence its developmental course.
Langley
Kate
K
Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK. langleyk@cardiff.ac.uk
Fowler
Tom A
TA
Grady
Deborah L
DL
Moyzis
Robert K
RK
Holmans
Peter A
PA
van den Bree
Marianne B M
MB
Owen
Michael J
MJ
O'Donovan
Michael C
MC
Thapar
Anita
A
D000293:Adolescent; D000367:Age Factors; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D003937:Diagnosis, Differential; D018450:Disease Progression; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008967:Molecular Biology / Q000379:methods*; D050638:Receptors, Dopamine D4 / Q000235:genetics; D050641:Receptors, Dopamine D5 / Q000235:genetics
C493599:DRD4 protein, human; C493605:DRD5 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5