National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Peking Union Medical College, Tsinghua University, Beijing, 100005, PR China.
Psychiatry Res. 2010 Sep 30;179(2):147-50. doi: 10.1016/j.psychres.2009.03.029. Epub 2010 May 18.
Negative symptoms commonly seen in chronic schizophrenia are related to prefrontal hypodopaminergia. Dysfunction of the catechol-O-methyltransferase (COMT) gene has long been thought to confer susceptibility to schizophrenia because of its catalytic activity for dopamine degradation. The present study is an attempt to perform a quantitative trait test for genetic association between the COMT gene and negative symptoms in a Chinese population. A total of 290 unrelated individuals with schizophrenia patients were recruited and their symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED programme to examine the correlation between the scored negative symptoms and the coding single nucleotide polymorphisms (SNPs) present in the COMT gene. The rs4633-rs4680 haplotype showed significant association with the overall score of negative symptoms, and four individual negative symptoms, including blunted affect, emotional withdrawal, poor rapport and passive/apathetic social withdrawal. SNP rs4680 (Val/Met) showed significant association with blunted affect. The present finding suggests that the COMT gene may a etiologically contribute to the severity of negative symptoms in schizophrenia, but its precise mechanism needs further investigating.
慢性精神分裂症中常见的阴性症状与前额叶多巴胺能低下有关。儿茶酚-O-甲基转移酶（COMT）基因的功能障碍因其对多巴胺降解的催化活性而被认为是精神分裂症的易感性因素。本研究试图在中国人群中对 COMT 基因与阴性症状之间的遗传关联进行定量性状测试。共招募了 290 名无关的精神分裂症患者，通过阳性和阴性综合征量表（PANSS）评估他们的症状。UNPHASED 程序进行了定量性状测试，以检查评分阴性症状与 COMT 基因中存在的编码单核苷酸多态性（SNP）之间的相关性。rs4633-rs4680 单倍型与阴性症状的总分以及包括情感迟钝、情感退缩、情感交流不良和被动/冷漠的社会退缩在内的四项阴性症状显著相关。SNP rs4680（Val/Met）与情感迟钝显著相关。本研究结果表明，COMT 基因可能在精神分裂症阴性症状的严重程度上具有病因学意义，但需要进一步研究其确切机制。
