TY - JOUR
T1 - Interacting effects of the dopamine transporter gene and psychosocial adversity on attention-deficit/hyperactivity disorder symptoms among 15-year-olds from a high-risk community sample
AU - Laucht, Manfred
AU - Skowronek, Markus H.
AU - Becker, Katja
AU - Schmidt, Martin H.
AU - Esser, Günter
AU - Schulze, Thomas G.
AU - Rietschel, Marcella
PY - 2007/5
Y1 - 2007/5
N2 - Context: Recent evidence suggests that gene X environment interactions could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with attention-deficit/hyperactivity disorder (ADHD). Objective: To examine whether psychosocial adversity moderated the effect of genetic variation in DAT1 on ADHD symptoms in adolescents from a high-risk community sample. Design: Prospective cohort study. Setting: Data were taken from the Mannheim Study of Children at Risk, an ongoing longitudinal study of the long-term outcomes of early risk factors followed up from birth on. Participants: Three hundred five adolescents (146 boys, 159 girls) participated in a follow-up assessment at age 15 years. Main Outcome Measures: Measures of ADHD symptoms according to DSM-IV were obtained using standardized structural interviews with adolescents and their parents. Psychosocial adversity was determined according to an "enriched" family adversity index as proposed by Rutter and Quinton. DNA was genotyped for the common DAT1 40-base pair (bp) variable number of tandem repeats (VNTR) polymorphism in the 3′ untranslated region; 3 previously described single nucleotide polymorphisms in exon 15, intron 9, and exon 9; and a novel 30-bp VNTR polymorphism in intron 8. Results: Adolescents homozygous for the 10-repeat allele of the 40-bp VNTR polymorphism who grew up in greater psychosocial adversity exhibited significantly more inattention and hyperactivity-impulsivity than adolescents with other genotypes or who lived in less adverse family conditions (significant interaction, P = .013.017). This gene X environment interaction was also observed in individuals homozygous for the 6-repeat allele of the 30-bp VNTR polymorphism and the haplotype comprising both markers. Conclusions: These findings provide initial evidence that environmental risks as described by the Rutter Family Adversity Index moderate the impact of the DAT1 gene on ADHD symptoms, suggesting a DAT1 effect only in those individuals exposed to psychosocial adversity.
AB - Context: Recent evidence suggests that gene X environment interactions could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with attention-deficit/hyperactivity disorder (ADHD). Objective: To examine whether psychosocial adversity moderated the effect of genetic variation in DAT1 on ADHD symptoms in adolescents from a high-risk community sample. Design: Prospective cohort study. Setting: Data were taken from the Mannheim Study of Children at Risk, an ongoing longitudinal study of the long-term outcomes of early risk factors followed up from birth on. Participants: Three hundred five adolescents (146 boys, 159 girls) participated in a follow-up assessment at age 15 years. Main Outcome Measures: Measures of ADHD symptoms according to DSM-IV were obtained using standardized structural interviews with adolescents and their parents. Psychosocial adversity was determined according to an "enriched" family adversity index as proposed by Rutter and Quinton. DNA was genotyped for the common DAT1 40-base pair (bp) variable number of tandem repeats (VNTR) polymorphism in the 3′ untranslated region; 3 previously described single nucleotide polymorphisms in exon 15, intron 9, and exon 9; and a novel 30-bp VNTR polymorphism in intron 8. Results: Adolescents homozygous for the 10-repeat allele of the 40-bp VNTR polymorphism who grew up in greater psychosocial adversity exhibited significantly more inattention and hyperactivity-impulsivity than adolescents with other genotypes or who lived in less adverse family conditions (significant interaction, P = .013.017). This gene X environment interaction was also observed in individuals homozygous for the 6-repeat allele of the 30-bp VNTR polymorphism and the haplotype comprising both markers. Conclusions: These findings provide initial evidence that environmental risks as described by the Rutter Family Adversity Index moderate the impact of the DAT1 gene on ADHD symptoms, suggesting a DAT1 effect only in those individuals exposed to psychosocial adversity.
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U2 - 10.1001/archpsyc.64.5.585
DO - 10.1001/archpsyc.64.5.585
M3 - Article
C2 - 17485610
AN - SCOPUS:34248172347
SN - 0003-990X
VL - 64
SP - 585
EP - 590
JO - Archives of General Psychiatry
JF - Archives of General Psychiatry
IS - 5
ER -