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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
Manfred Laucht, PhD;
Markus H. Skowronek, PhD;
Katja Becker, MD;
Martin H. Schmidt, MD, PhD;
Günter Esser, PhD;
Thomas G. Schulze, MD;
Marcella Rietschel, MD
Arch Gen Psychiatry. 2007;64(5):585-590.
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.
Author Affiliations: Department of Child and Adolescent Psychiatry and Psychotherapy (Drs Laucht, Becker, and Schmidt) and Division of Genetic Epidemiology in Psychiatry (Drs Skowronek, Schulze, and Rietschel), Central Institute of Mental Health, Mannheim, Germany; and Department of Psychology, Division of Clinical Psychology, University of Potsdam, Potsdam, Germany (Dr Esser).
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