Jin J, Liu L, Gao Q, Chan R C K, Li H, Chen Y, Wang Y, Qian Q
Peking University Sixth Hospital/Institute of Mental Health.
National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital).
Genes Brain Behav. 2016 Feb;15(2):271-9. doi: 10.1111/gbb.12270. Epub 2016 Jan 20.
Children with attention-deficit/hyperactivity disorder (ADHD) usually display deficits in executive function (EF), which are primarily mediated by prefrontal cortex (PFC). The functional polymorphism of catechol-O-methyltransferase (COMT), Val158Met (rs4680), leads to observed polymorphic differences in the degradation of dopamine within PFC. This study aimed to explore the effect of rs4680 on EF using case-control design. In addition, considering the dynamic development of EF, we also attempted to investigate whether this genetic influence changes during development or not. A total of 597 ADHD children and 154 unaffected controls were recruited. The EF was evaluated using Rey-Osterrieth complex figure test (RCFT), trail making test (TMT) and Stroop color and word test for working memory, shifting and inhibition. Association between genotype and EF was analyzed using analysis of covariance (ancova). The results showed significant interaction effect of genotype and ADHD diagnosis on RCFT performance (P < 0.001). However, the associated genotypes between ADHD and controls were divergent. In ADHD, the Met carriers performed better than the Val homozygotes on detail immediate [(10.38 ± 6.90) vs. (9.33 ± 6.92), P = 0.007] and detail delay [(9.96 ± 6.86) vs. (8.86 ± 6.89), P = 0.004], while Val homozygotes showed better performance compared with Met carrier controls [for detail immediate (14.55 ± 6.18) vs. (11.10 ± 6.45), P<0.001; for detail delay (14.31 ± 5.96) vs. (11.31 ± 6.96), P = 0.001]. We did not find significant interaction between genetic variant and development. COMT Val158Met (rs4680) may have divergent effect on working memory in ADHD children compared with healthy controls.
患有注意力缺陷多动障碍（ADHD）的儿童通常在执行功能（EF）方面存在缺陷，而执行功能主要由前额叶皮质（PFC）介导。儿茶酚-O-甲基转移酶（COMT）的功能性多态性Val158Met（rs4680）导致前额叶皮质内多巴胺降解存在多态性差异。本研究旨在采用病例对照设计探讨rs4680对执行功能的影响。此外，考虑到执行功能的动态发展，我们还试图研究这种基因影响在发育过程中是否会发生变化。共招募了597名ADHD儿童和154名未受影响的对照。使用雷-奥斯特里思复杂图形测试（RCFT）、连线测验（TMT）和斯特鲁普颜色和文字测试来评估工作记忆、转换和抑制方面的执行功能。使用协方差分析（ancova）分析基因型与执行功能之间的关联。结果显示基因型与ADHD诊断对RCFT表现有显著的交互作用（P < 0.001）。然而，ADHD患者与对照组之间的相关基因型存在差异。在ADHD患者中，携带Met的个体在即时细节方面表现优于Val纯合子[（10.38 ± 6.90）对（9.33 ± 6.92），P = 0.007]和延迟细节方面[（9.96 ± 6.86）对（8.86 ± 6.89），P = 0.004]，而与携带Met的对照相比，Val纯合子表现更好[即时细节方面（14.55 ± 6.18）对（11.10 ± 6.45），P<0.001；延迟细节方面（14.31 ± 5.96）对（11.31 ± 6.96），P = 0.001]。我们未发现基因变异与发育之间存在显著交互作用。与健康对照相比，COMT Val158Met（rs4680）可能对ADHD儿童的工作记忆有不同影响。
