Papaleo Francesco, Sannino Sara, Piras Fabrizio, Spalletta Gianfranco
Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genova, Italy.
Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genova, Italy.
Eur Neuropsychopharmacol. 2015 Dec;25(12):2349-63. doi: 10.1016/j.euroneuro.2015.10.005. Epub 2015 Oct 27.
Different genetic variations in the catechol-O-methyltransferase (COMT) gene have been indicated to functionally regulate the encoded enzyme. Despite the vast literature on the single nucleotide COMT ValMet polymorphism, the impact of complex haplotypes on cognitive functions has been overlooked. Here we contrasted the effects of complex COMT haplotypes with the ValMet polymorphism on cognitive functions and their interaction with menopause, in healthy subjects and patients with schizophrenia. Healthy adults (N=229) as well as patients with schizophrenia (N=172) underwent a comprehensive cognitive assessment taking into account the menopausal state. Functional COMT variations selectively modulated working memory and executive functions. Strikingly, these effects were present only in adult men but not in women before menopause, in both healthy subjects and patients with schizophrenia. Importantly, the same pattern of COMT-dependent effects present in men reappeared in women after menopause. Thus, functional COMT mutations seem to modulate cognitive functions depending on the hormonal status. These data clarify the importance of taking into account the combined effect of sex, hormonal status and genetics.
儿茶酚-O-甲基转移酶（COMT）基因的不同遗传变异已被证明可在功能上调节所编码的酶。尽管关于COMT基因单核苷酸ValMet多态性已有大量文献，但复杂单倍型对认知功能的影响却被忽视了。在此，我们对比了复杂COMT单倍型与ValMet多态性对认知功能的影响，以及它们与绝经的相互作用，研究对象为健康受试者和精神分裂症患者。健康成年人（N = 229）以及精神分裂症患者（N = 172）接受了全面的认知评估，评估时考虑了绝经状态。功能性COMT变异选择性地调节工作记忆和执行功能。令人惊讶的是，在健康受试者和精神分裂症患者中，这些效应仅在成年男性中存在，而绝经前的女性中不存在。重要的是，男性中存在的依赖COMT的效应模式在绝经后的女性中再次出现。因此，功能性COMT突变似乎根据激素状态调节认知功能。这些数据阐明了考虑性别、激素状态和遗传学综合效应的重要性。
