COMT Val108/158Met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome
COMT Val108/158Met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome
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DOI：
10.1016/j.biopsych.2005.03.020
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发表时间：
2005-07-01
影响因子：
10.6
通讯作者：
Skuse, D
中科院分区：
文献类型：
--
作者：
Baker, K;Baldeweg, T;Skuse, D
背景：22q11.2微缺失极大地增加了成年早期患精神分裂症的风险（相对风险约为25 - 30）。我们假设在精神分裂症发病之前，22q11缺失综合征（22q11DS）患者会表现出与普通人群中精神分裂症高危个体共有的特定认知和神经生理异常（内表型）。我们还预测，位于缺失染色体片段内的儿茶酚 - O - 甲基转移酶Val(108/158)Met多态性会改变内表型特征的严重程度。
方法：将22q11DS青少年和青年（年龄13 - 21岁）与年龄和智商匹配的对照受试者在与特发性精神分裂症风险相关的指标上进行比较。
结果：22q11DS受试者比对照受试者表现出更差的言语工作记忆和表达性语言能力。听觉失匹配负波（MMN）事件相关电位在额叶电极处降低，但在颞叶部位正常。在单条完整的22号染色体上存在COMT108/158 Met等位基因与更显著的MMN波幅降低和更差的神经心理学表现相关。COMT Val(108/158)Met等位基因均不影响精神症状。
结论：22q11DS与类似于特发性精神分裂症的神经发育特征相关。COMT val(108/158)Met多态性改变了精神分裂症内表型的严重程度，表明儿茶酚胺调节受损导致了22q11DS的神经精神风险。
Background: Microdeletions at 22q11.2 greatly increase the risk of schizophrenia in early adulthood (relative risk approximate to 25-30). We hypothesized that before before the onset of schizophrenia, individuals with 22q11DS would manifest specific cognitive and neurophysiological anomalies (endophenotypes) in common with individuals at high risk for schizophrenia in the general population. We further predicted that the catechol-O-methyltransferase Val(108/158) Met polymorphism, located within the deleted chromosomal segment, would modify the severity of endophenotypic features.Methods: 22q11DS adolescents and young adults (aged 13-21) were compared with age- and IQ-matched control subjects on measures that are associated with risk of idiopathic schizophrenia.Results: 22q11DS subjects displayed poorer verbal working memory and expressive language performance than control subjects. Auditory mismatch negativity (MMN) event-related potentials were reduced at frontal electrodes but were intact at temporal sites. Presence of the COMT108/158 Met allele on the single intact chromosome 22 was associated with more marked MMN amplitude reduction and poorer neuropsychological performance. Neither COMT Val(108/158) Met allele influenced psychiatric symptoms.Conclusions: 22q11DS is associated with neurodevelopmental characteristics that are similar to idiopathic schizophrenia. The COMT val(108/158) Met polymorphism modifies the severity of endophenotypes for schizophrenia, indicating that impaired catecholamine regulation contributes to neuropsychiatric risk in 22q11DS.