Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
J Psychiatr Res. 2013 Jul;47(7):989-94. doi: 10.1016/j.jpsychires.2013.02.002. Epub 2013 Mar 26.
The functional variant Val(158)Met in the coding sequence of COMT gene is involved in the modulation of dopamine availability in the prefrontal cortex in both clinical and general population samples. It has been suggested that the interplay between this genotype and early environmental factors could be used to predict the observed variation in cognitive flexibility. However, other genetic variants and environmental factors may confound the association and produce the inconsistent results commonly found in the literature. In the present study we aimed at testing putative interaction mechanisms between childhood maltreatment and COMT genotypic variability that might explain a proportion of the observed variability of cognitive flexibility in the population. Our design was based on a sample of adult monozygotic twins, which allowed us to test these effects free from potential genetic and shared-environmental confounding factors. Results showed that unique environmental effects of childhood maltreatment significantly impacted cognitive performance among Met/Met subjects. Interestingly, the direction of the association indicated that exposure to early stressful experiences was associated with enhanced cognitive flexibility in this genotype group. These results suggest that COMT may operate as a plasticity gene that provides differential cognitive capacity to respond to environmental stressors.
COMT 基因编码序列中的功能性变体 Val(158)Met 参与了前额叶皮质多巴胺可用性的调节，无论是在临床样本还是一般人群样本中都是如此。有人提出，这种基因型与早期环境因素的相互作用可以用来预测认知灵活性的观察到的变化。然而，其他遗传变异和环境因素可能会混淆这种关联，并产生文献中常见的不一致结果。在本研究中，我们旨在测试儿童期虐待和 COMT 基因型变异性之间可能存在的相互作用机制，这些机制可能可以解释人群中认知灵活性观察到的变异性的一部分。我们的设计基于成年同卵双胞胎的样本，这使我们能够在不受潜在遗传和共同环境混杂因素影响的情况下测试这些效应。结果表明，儿童期虐待的独特环境效应显著影响了 Met/Met 受试者的认知表现。有趣的是，关联的方向表明，早期应激经历的暴露与这种基因型组认知灵活性的增强有关。这些结果表明，COMT 可能作为一种可塑性基因发挥作用，为应对环境应激源提供不同的认知能力。
