Sonuga-Barke Edmund J S, Oades Robert D, Psychogiou Lamprini, Chen Wai, Franke Barbara, Buitelaar Jan, Banaschewski Tobias, Ebstein Richard P, Gil Michael, Anney Richard, Miranda Ana, Roeyers Herbert, Rothenberger Aribert, Sergeant Joseph, Steinhausen Hans Christoph, Thompson Margaret, Asherson Philip, Faraone Stephen V
Developmental Brain-Behaviour Laboratory, School of Psychology, University of Southampton, Southampton, UK.
J Child Psychol Psychiatry. 2009 Sep;50(9):1052-63. doi: 10.1111/j.1469-7610.2009.02095.x. Epub 2009 Apr 14.
Mothers' positive emotions expressed about their children with attention deficit/hyperactivity disorder (ADHD) are associated with a reduced likelihood of comorbid conduct problems (CP). We examined whether this association with CP, and one with emotional problems (EMO), is moderated by variants within three genes, previously reported to be associated with ADHD and to moderate the impact of environmental risks on conduct and/or emotional problems; the dopamine transporter gene (SLC6A3/DAT1), the dopamine D4 receptor gene (DRD4) and the serotonin transporter gene (SLC6A4/5HTT).
Seven hundred and twenty-eight males between the ages of 5 and 17 with a DSM-IV research diagnosis of combined type ADHD were included in these analyses. Parents and teachers rated children's conduct and emotional problems. Positive maternal expressed emotion (PMEE) was coded by independent observers on comments made during a clinical assessment with the mother based on current or recent medication-free periods.
Sensitivity to the effects of PMEE on CP was moderated by variants of the DAT1 and 5HTT genes. Only children who did not carry the DAT1 10R/10R or the 5HTT l/l genotypes showed altered levels of CP when exposed to PMEE. The effect was most marked where the child with ADHD had both these genotypes. For EMO, sensitivity to PMEE was found only with those who carried the DAT1 9R/9R. There was no effect of DRD4 on CP or EMO.
The gene-environment interactions observed suggested that genetic make-up can alter the degree of sensitivity an ADHD patients has to their family environment. Further research should focus on distinguishing general sensitivity genotypes from those conferring risk or protective qualities.
母亲对患有注意力缺陷多动障碍(ADHD)的孩子表达的积极情绪与共患品行问题(CP)的可能性降低有关。我们研究了这种与CP以及与情绪问题(EMO)的关联是否会受到三个基因变异的调节,这三个基因先前被报道与ADHD相关,并能调节环境风险对品行和/或情绪问题的影响;多巴胺转运体基因(SLC6A3/DAT1)、多巴胺D4受体基因(DRD4)和5-羟色胺转运体基因(SLC6A4/5HTT)。
纳入728名年龄在5至17岁之间、经DSM-IV研究诊断为复合型ADHD的男性进行分析。父母和教师对孩子的品行和情绪问题进行评分。积极的母亲表达性情绪(PMEE)由独立观察者根据母亲在临床评估期间基于当前或近期无药物治疗期的评论进行编码。
DAT1和5HTT基因的变异调节了PMEE对CP影响的敏感性。只有那些没有携带DAT1 10R/10R或5HTT l/l基因型的孩子在接触PMEE时CP水平发生了变化。当患有ADHD的孩子同时具有这两种基因型时,这种影响最为明显。对于EMO,仅在那些携带DAT1 9R/9R的孩子中发现对PMEE敏感。DRD4对CP或EMO没有影响。
观察到的基因-环境相互作用表明,基因构成可以改变ADHD患者对其家庭环境的敏感程度。进一步的研究应侧重于区分一般敏感性基因型与具有风险或保护特质的基因型。