Dopamine transporter gene polymorphism moderates the effects of severe deprivation on ADHD symptoms: developmental continuities in gene-environment interplay.
Early institutional deprivation is a risk factor for Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. However not all individuals are affected. We tested the hypothesis that this heterogeneity is influenced by gene x environment (GxE) interaction and that genetic polymorphisms involved in dopamine neurotransmission moderate the effects of severe early institutional deprivation on symptoms of ADHD (sADHD). Using a prospective-longitudinal design sADHD were measured at ages 6, 11, and 15 years in a sample of individuals who experienced severe institutional deprivation (up to 42 months of age) in Romanian orphanages and a non-institutionalized comparison group. Individuals were genotyped for polymorphisms in the dopamine D4 receptor (DRD4 48-bp VNTR in exon 3) and dopamine transporter gene (DAT1 haplotypes combining a 40-bp VNTR in 3'UTR and a 30-bp VNTR in intron 8). The risk for sADHD associated with early institutional deprivation was moderated by the DAT1 but not the DRD4 genotypes; an effect that was first apparent in early-, and persisted to mid-adolescence. The results (i) provide evidence for developmental continuities in G x E interaction, (ii) explain some of the heterogeneity in ADHD outcomes following institutional deprivation and, (iii) add to our understanding of environmental determinants of sADHD.
Stevens
Suzanne E
SE
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK. s.stevens@psychology.bbk.ac.uk
Kumsta
Robert
R
Kreppner
Jana M
JM
Brookes
Keeley J
KJ
Rutter
Michael
M
Sonuga-Barke
Edmund J S
EJ
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D054540:Child, Orphaned; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic; D011610:Psychosocial Deprivation; D050638:Receptors, Dopamine D4 / Q000235:genetics / Q000378:metabolism; D012383:Romania; D012931:Social Environment
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4