Bilder Robert M, Volavka Jan, Czobor Pál, Malhotra Anil K, Kennedy James L, Ni Xingqun, Goldman Robert S, Hoptman Matthew J, Sheitman Brian, Lindenmayer Jean-Pierre, Citrome Leslie, McEvoy Joseph P, Kunz Michal, Chakos Miranda, Cooper Thomas B, Lieberman Jeffrey A
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
Biol Psychiatry. 2002 Oct 1;52(7):701-7. doi: 10.1016/s0006-3223(02)01416-6.
Neurocognitive deficits are recognized as a cardinal feature of schizophrenia, but the determinants of these deficits remain unknown. Recent reports have suggested that a functional polymorphism, Val(158)Met in exon III of the catechol-O-methyltransferase gene, shares approximately 4% variance with performance on the Wisconsin Card Sorting Test. These findings led to suggestions that the catechol-O-methyltransferase polymorphism may exert its effects by modulating prefrontal dopamine function, but few other neurocognitive measures have been examined, leaving open questions about phenotypic specificity.
We examined the effects of the catechol-O-methyltransferase Val(158)Met polymorphism in 58 individuals with chronic schizophrenia who completed a battery of 15 neurocognitive tests, which were reduced to four reliable neurocognitive domain scores. We examined the effects of genotype on these four domains and on global neurocognitive ability.
The Met allele was associated with better performance in the Processing Speed and Attention domain, but not with other domain scores measuring executive and visuoperceptual functions, declarative verbal learning and memory, simple motor ability, or global neurocognitive function. Genotype shared approximately 11% of variance with Processing Speed and Attention scores, and approximately 2% of variance with Wisconsin Card Sorting Test scores.
The findings provide independent support for the hypothesis that the catechol-O-methyltransferase Val(158)Met polymorphism influences neurocognitive function in schizophrenia, and suggest that the functional effects may be expressed on measures of Processing Speed and Attention. This information may prompt reconsideration of the "prefrontal dopamine" hypothesis and invites examination of a broader range of effects in efforts to refine the neurocognitive phenotype that is most relevant to variation in catechol-O-methyltransferase expression.
神经认知缺陷被认为是精神分裂症的主要特征，但这些缺陷的决定因素仍不清楚。最近的报告表明，儿茶酚-O-甲基转移酶基因外显子III中的功能性多态性Val(158)Met与威斯康星卡片分类测验的表现约有4%的方差共享。这些发现提示儿茶酚-O-甲基转移酶多态性可能通过调节前额叶多巴胺功能发挥作用，但很少有其他神经认知指标被研究，关于表型特异性的问题仍未解决。
我们检测了58例慢性精神分裂症患者中儿茶酚-O-甲基转移酶Val(158)Met多态性的影响，这些患者完成了一系列15项神经认知测试，这些测试被简化为四个可靠的神经认知领域得分。我们检测了基因型对这四个领域以及整体神经认知能力的影响。
Met等位基因与加工速度和注意力领域的更好表现相关，但与其他测量执行和视觉感知功能、陈述性言语学习和记忆、简单运动能力或整体神经认知功能的领域得分无关。基因型与加工速度和注意力得分约有11%的方差共享，与威斯康星卡片分类测验得分约有2%的方差共享。
这些发现为儿茶酚-O-甲基转移酶Val(158)Met多态性影响精神分裂症神经认知功能的假说提供了独立支持，并表明功能效应可能在加工速度和注意力测量中表现出来。这些信息可能促使重新考虑“前额叶多巴胺”假说，并促使人们在努力完善与儿茶酚-O-甲基转移酶表达变异最相关的神经认知表型时，对更广泛的效应进行研究。
