Association study between COMT 158Met and creativity scores in bipolar disorder and healthy controls

Background Bipolar disorder (BD) patients have been reported to be associated higher creativity abilities, and recent data tend to support the hypothesis that dopaminergic system that could be associated with creativity. Catechol-O-methyltransferase (COMT) is one of the major enzymes involved in the metabolic degradation of dopamine. The COMT gene polymorphism (rs4680 or Val158Met) Met allele is reported to cause decreased activity of this enzyme in prefrontal cortex and improve performance in several cognitive domains. Objective The objective of this study was to evaluate the influence of Val158Met on creativity in BD type I and healthy controls. Methods Ninety-seven healthy volunteers and 120 BD type I were genotyped for COMT rs4680 and tested for creativity (Barrow Welsh Art Scale – BWAS) and intelligence Wechsler Abbreviated Scale of Intelligence (WASI). Results COMT Met allele positively influenced creativity scores in healthy controls but not in BD subjects during mood episodes and euthymia. The presence of allele Met did not influence IQ scores. No influence of IQ total score on creativity was observed. Limitations control group presented higher IQ scores and euthymic group was under medication use. Discussion Our research suggests positive effect of COMT rs4680 (allele Met) on creativity scores in healthy controls. One possible interpretation is that creativity is more likely to be associated with lesser degrees of bipolarity. The fact that the same results were not observed in BD may be associated to dysfunctions in the dopaminergic system that characterizes this disorder. Further studies with larger samples and other types of BD should explore the role of the dopaminergic system in creativity.

研究背景：已有研究表明，双相情感障碍（Bipolar disorder, BD）患者往往具备更高的创造力水平，近期相关数据也支持“多巴胺能系统可能与创造力存在关联”这一假说。儿茶酚-O-甲基转移酶（Catechol-O-methyltransferase, COMT）是参与多巴胺代谢降解的主要酶类之一。COMT基因多态性（rs4680即Val158Met）中的Met等位基因可降低前额叶皮层内该酶的活性，并改善多个认知领域的表现。
研究目的：本研究旨在评估Val158Met多态性对I型双相情感障碍患者及健康对照者创造力水平的影响。
研究方法：招募97名健康志愿者与120名I型双相情感障碍患者，对其进行COMT rs4680基因分型，并采用巴罗-威尔士艺术量表（Barrow Welsh Art Scale, BWAS）评估创造力、韦氏简智力量表（Wechsler Abbreviated Scale of Intelligence, WASI）评估智力水平。
研究结果：COMT Met等位基因可正向影响健康对照者的创造力得分，但在处于心境发作期及心境稳定期的双相情感障碍患者中未观察到此效应。Met等位基因的存在对总智商得分无显著影响，且总智商得分与创造力得分之间未发现关联。
研究局限：本研究存在如下局限：对照组的智商得分显著高于双相障碍组，且心境稳定组受试者均在接受药物治疗。
讨论：本研究结果提示，COMT rs4680的Met等位基因对健康对照者的创造力得分具有正向作用。一种可能的解释为：创造力更可能与较轻程度的双相特质相关。而在双相情感障碍患者中未观察到相同效应，这可能与该疾病特征性的多巴胺能系统功能异常有关。未来需开展更大样本量、纳入其他类型双相障碍的相关研究，以进一步探讨多巴胺能系统在创造力中的作用。