Lu Brett Y, Martin Kimberly E, Edgar J Christopher, Smith Ashley K, Lewis Stephen F, Escamilla Michael A, Miller Gregory A, Cañive Jose M
Department of Psychiatry, University of New Mexico, Albuquerque, New Mexico 87108, USA.
Biol Psychiatry. 2007 Oct 1;62(7):822-5. doi: 10.1016/j.biopsych.2006.11.030. Epub 2007 Apr 19.
Studies have implicated prefrontal dopamine in cortical information filtering. Deficit in stimulus filtering, an endophenotype of schizophrenia, can be demonstrated using the auditory P50 paired-click gating paradigm. The role of prefrontal dopamine on P50 gating was investigated, using catechol-O-methyltransferase (COMT) valine (val)(158)methionine (met) polymorphism as a predictor of prefrontal dopamine activity.
Twenty-five comparison and 42 schizophrenia subjects underwent P50 gating measurement and COMT genotyping.
In the combined sample, COMT polymorphism accounted for a unique 10% of gating variance (p = .02), after variance due to diagnosis, smoking status, and antipsychotic use was removed. Valine homozygous individuals exhibited the greatest gating deficit.
Valine homozygous individuals are more likely to have gating deficits, supporting COMT as a genetic determinant of the P50 endophenotype, as well as a role for prefrontal dopamine in auditory filtering.
研究表明前额叶多巴胺参与皮层信息过滤。刺激过滤缺陷是精神分裂症的一种内表型，可通过听觉P50配对点击门控范式来证明。利用儿茶酚-O-甲基转移酶（COMT）缬氨酸（val）（158）蛋氨酸（met）多态性作为前额叶多巴胺活性的预测指标，研究了前额叶多巴胺对P50门控的作用。
25名对照者和42名精神分裂症患者接受了P50门控测量和COMT基因分型。
在合并样本中，排除诊断、吸烟状况和抗精神病药物使用导致的方差后，COMT多态性占门控方差的独特比例为10%（p = .02）。缬氨酸纯合个体表现出最大的门控缺陷。
缬氨酸纯合个体更有可能出现门控缺陷，支持COMT作为P50内表型的遗传决定因素，以及前额叶多巴胺在听觉过滤中的作用。
