Catechol-O-methyltransferase polymorphisms and some implications for cognitive therapeutics.
Catechol-O-methyltransferase polymorphisms and some implications for cognitive therapeutics.
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DOI：
10.1016/j.nurx.2005.12.010
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Goldberg, Terry E
中科院分区：
文献类型：
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作者：
Diaz-Asper, Catherine M;Weinberger, Daniel R;Goldberg, Terry E
儿茶酚-O-甲基转移酶（COMT）是一种参与多巴胺降解的基因，可能会增加患精神分裂症的易感性，并影响参与工作记忆的神经元功能。COMT基因的一种常见变体（瓦尔（108/158）met）已被广泛报道影响前额叶介导的工作记忆功能，高活性瓦尔等位基因与在许多对更新和目标检测敏感的测试中表现最差相关。COMT瓦尔（108/158）met的药理学操作也可靠地产生了认知功能的改变，与前额叶多巴胺信号传导的倒U功能一致。此外，越来越多的证据表明，COMT瓦尔（108/158）met基因型可能影响精神分裂症患者对抗精神病药物治疗的认知反应，met等位基因负荷预测药物治疗的最大改善。最近，COMT基因上的其他单核苷酸多态性（SNP）已成为精神分裂症的可能风险等位基因，尽管对它们是否以类似于COMT瓦尔（108/158）met的方式影响前额认知知之甚少。初步证据表明，在注意力和目标检测的选择测试中，基因5'区域的SNP发挥了适度的作用。单倍型效应也可能占测试性能方差的适度百分比，并且是未来研究的重要领域。
Catechol-O-methyltransferase (COMT) is a gene involved in the degradation of dopamine and may both increase susceptibility to develop schizophrenia and affect neuronal functions involved in working memory. A common variant of the COMT gene (val(108/158)met) has been widely reported to affect pre-frontally mediated working memory function, with the high-activity val allele associated with poorest performance across a number of tests sensitive to updating and target detection. Pharmacological manipulations of COMT val(108/158)met also have reliably produced alterations in cognitive function, in line with an inverted U function of prefrontal dopamine signaling. Furthermore, there is accumulating evidence that COMT val(108/158)met genotype may influence the cognitive response to antipsychotic treatment in schizophrenia patients, with met allele load predicting the greatest improvement with medication. Recently, other single-nucleotide polymorphisms (SNPs) across the COMT gene have emerged as possible risk alleles for schizophrenia, although little is known about whether they affect prefrontal cognition in a manner similar to COMT val(108/158)met. Preliminary evidence suggests a modest role for a SNP in the 5' region of the gene on select tests of attention and target detection. Haplotype effects also may account for a modest percentage of the variance in test performance, and are an important area for future study.