Centre for Medical Research/Western Australian Institute for Medical Research, The University of Western Australia, Perth, WA, Australia.
Mol Psychiatry. 2011 Aug;16(8):860-6. doi: 10.1038/mp.2010.70. Epub 2010 Jun 15.
Linkage of 10q22-q23 to schizophrenia and the recently reported association of Neuregulin 3 (NRG3) polymorphisms with high 'delusion factor' scores led us to attempt replication and further refinement of these findings in a sample of 411 schizophrenic patients and 223 nonpsychiatric control subjects. Using quantitative cognitive traits, patients were grouped into a cluster with pervasive cognitive deficit (CD) and a cluster with relatively spared cognition (CS). We found a significant association between rs6584400 and schizophrenia, with a trend for rs10883866. Post hoc analysis revealed that this result was mainly due to the CS cluster, characterized by elevated scores on Schneiderian first-rank symptoms, salience of complex delusions and positive thought disorder--thus closely related to the 'delusion factor'. In addition, both rs6584400 and rs10883866 were associated with the degraded-stimulus continuous performance task in which 'risk' alleles were associated with better than average performance in patients and worse performance in controls. This suggests that NRG3 may be modulating early attentional processes for perceptual sensitivity and vigilance, with opposite effects in affected individuals and healthy controls. The two single-nucleotide polymorphisms are in close proximity to the alternative first exons of the NRG3-a, -b and -d isoforms, of which the human brain-specific NRG-b appears to be the most interesting candidate.
10q22-q23 与精神分裂症的连锁以及最近报道的 Neuregulin 3（NRG3）多态性与高“妄想因子”评分之间的关联，促使我们在 411 名精神分裂症患者和 223 名非精神科对照者样本中尝试复制和进一步细化这些发现。使用定量认知特征，将患者分为具有普遍认知缺陷（CD）的聚类和具有相对保留认知的聚类（CS）。我们发现 rs6584400 与精神分裂症之间存在显著关联，rs10883866 存在关联趋势。事后分析表明，这一结果主要是由于 CS 聚类所致，其特征是 Schneiderian 一级症状评分升高、复杂妄想的突出和阳性思维障碍——与“妄想因子”密切相关。此外，rs6584400 和 rs10883866 均与降级刺激连续表现任务相关，其中“风险”等位基因与患者的平均表现优于平均表现相关，而与对照组的表现较差相关。这表明 NRG3 可能调节了感知敏感性和警觉性的早期注意过程，在受影响个体和健康对照者中具有相反的作用。这两个单核苷酸多态性与 NRG3-a、-b 和 -d 异构体的替代第一外显子密切相关，其中人脑特异性 NRG-b 似乎是最有趣的候选者。
