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
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
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DOI：
10.1001/archpsyc.64.5.585
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发表时间：
2007-05-01
影响因子：
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通讯作者：
Rietschel, Marcella
中科院分区：
文献类型：
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作者：
Laucht, Manfred;Skowronek, Markus H.;Rietschel, Marcella
背景：最近的证据表明，基因 X 与环境的相互作用可以解释多巴胺转运蛋白 (DAT1) 基因与注意力缺陷/多动障碍 (ADHD) 之间的关联研究的不一致结果。1目的：检查社会心理逆境是否调节了高危社区样本青少年中 DAT1 遗传变异对 ADHD 症状的影响。设计：前瞻性队列研究。背景：数据取自曼海姆高危儿童研究，这是一项正在进行的纵向研究参与者：305 名青少年（146 名男孩，159 名女孩）在 15 岁时参加了后续评估。主要结果指标：根据 DSM-IV 对 ADHD 症状的测量是通过对青少年及其父母进行标准化结构访谈获得的。社会心理逆境是根据拉特和昆顿提出的“丰富的”家庭逆境指数来确定的。对 DNA 的 3' 非翻译区常见 DAT1 40 碱基对 (bp) 可变串联重复数 (VNTR) 多态性进行基因分型； 3先前描述的外显子15、内含子9和外显子9的单核苷酸多态性；以及内含子 8 中新的 30-bp VNTR 多态性。结果：40-bp VNTR 多态性的 10 重复等位基因纯合的青少年，在更大的心理社会逆境中长大，比具有其他基因型或生活在不太不利的家庭条件的青少年表现出明显更多的注意力不集中和多动冲动（显着交互作用，P=.013-017）。这种基因 X 环境相互作用也在 30 bp VNTR 多态性的 6 重复等位基因纯合子和包含两个标记的单倍型的个体中观察到。结论：这些发现提供了初步证据，表明 Rutter 家庭逆境指数描述的环境风险减轻了 DAT1 基因对 ADHD 症状的影响，表明 DAT1 只对那些暴露于社会心理逆境的个体产生影响。
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).1bjective: 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.