Dopamine Transporter Gene Polymorphism Moderates the Effects of Severe Deprivation on ADHD Symptoms: Developmental Continuities in Gene-Environment Interplay

TY - JOUR

T1 - Dopamine Transporter Gene Polymorphism Moderates the Effects of Severe Deprivation on ADHD Symptoms: Developmental Continuities in Gene-Environment Interplay

AU - Stevens, Suzanne E.

AU - Kumsta, Robert

AU - Kreppner, Jana M.

AU - Brookes, Keeley J.

AU - Rutter, Michael

AU - Sonuga-Barke, Edmund J. S.

PY - 2009/9/5

Y1 - 2009/9/5

N2 - 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 (DRD448-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. (C) 2009 Wiley-Liss, Inc.

AB - 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 (DRD448-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. (C) 2009 Wiley-Liss, Inc.

U2 - 10.1002/ajmg.b.31010

DO - 10.1002/ajmg.b.31010

M3 - Article

SN - 1552-485X

VL - 150B

SP - 753

EP - 761

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

IS - 6

ER -