Kircher T, Markov V, Krug A, Eggermann T, Zerres K, Nöthen M M, Skowronek M H, Rietschel M
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.
Psychol Med. 2009 Oct;39(10):1657-65. doi: 10.1017/S0033291709005388. Epub 2009 Apr 1.
Schizophrenia is a complex disorder with a high heritability. Family members have an increased risk not only for schizophrenia per se but also for schizophrenia spectrum disorders. Impairment of neuropsychological functions found in schizophrenia patients are also frequently observed in their relatives. The dystrobrevin-binding protein 1 (DTNBP1) gene located at chromosome 6p22.3 is one of the most often replicated vulnerability genes for schizophrenia. In addition, this gene has been shown to modulate general cognitive abilities both in healthy subjects and in patients with schizophrenia.
In a sample of 521 healthy subjects we investigated an association between the DTNBP1 genotype [single nucleotide polymorphism (SNP) rs1018381], personality traits [using the NEO Five-Factor Inventory (NEO-FFI) and the Schizotypal Personality Questionnaire - Brief Version (SPQ-B)] and cognitive function (estimated IQ, verbal fluency, attention, working memory and executive function).
Significantly lower scores on the SPQ-B (p=0.0005) and the Interpersonal Deficit subscale (p=0.0005) in carriers of the A-risk allele were detected. There were no differences in any of the cognitive variables between groups.
The results indicate that genetic variation of the DTNBP1 genotype might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.
精神分裂症是一种遗传性很高的复杂疾病。家庭成员不仅患精神分裂症本身的风险增加，患精神分裂症谱系障碍的风险也增加。精神分裂症患者中发现的神经心理功能损害在其亲属中也经常观察到。位于6号染色体p22.3的肌动蛋白结合蛋白1（DTNBP1）基因是精神分裂症最常被复制的易感基因之一。此外，该基因已被证明在健康受试者和精神分裂症患者中均能调节一般认知能力。
在521名健康受试者的样本中，我们研究了DTNBP1基因型[单核苷酸多态性（SNP）rs1018381]、人格特质[使用大五人格量表（NEO-FFI）和分裂型人格问卷简版（SPQ-B）]与认知功能（估计智商、语言流畅性、注意力、工作记忆和执行功能）之间的关联。
检测到A风险等位基因携带者的SPQ-B得分（p = 0.0005）和人际缺陷分量表得分（p = 0.0005）显著较低。两组之间在任何认知变量上均无差异。
结果表明，DTNBP1基因型的基因变异可能在人群水平上对精神分裂症内表型产生基因特异性调节作用。
