Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany.
Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany.
Schizophr Res. 2019 Jun;208:67-75. doi: 10.1016/j.schres.2019.04.018. Epub 2019 May 7.
Schizotypy is a multidimensional risk phenotype distributed in the general population, constituting of subclinical, psychotic-like symptoms. It is associated with psychosis proneness, and several risk genes for psychosis are associated with schizotypy in non-clinical populations. Schizotypy might also modulate cognitive abilities as it is associated with attentional deficits in healthy subjects. In this study, we tested the hypothesis that established genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737 are associated with psychometric schizotypy and that schizotypy mediates their effect on attention or vice versa. In 615 healthy subjects from the FOR2107 cohort study, we analysed the genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737, psychometric schizotypy (schizotypal personality questionnaire-brief SPQB), and a neuropsychological measure of sustained and selective attention (d2 test). ZNF804A rs1344706 C (non-risk) alleles were significantly associated with higher SPQ-B Cognitive-Perceptual subscores in women and with attention deficits in both sexes. This schizotypy dimension also mediated the effect of ZNF804A on attention in women, but not in men. CACNA1C rs1006737-A showed a significant sex-modulated negative association with Interpersonal schizotypy only in men, and no effect on attention. Our multivariate model demonstrates differential genetic contributions of two psychosis risk genes to dimensions of schizotypy and, partly, to attention. This supports a model of shared genetic influence between schizotypy and cognitive functions impaired in schizophrenia.
分裂型特质是一种分布在普通人群中的多维风险表型，由亚临床、类精神病症状组成。它与精神病易感性有关，几种精神病的风险基因与非临床人群中的分裂型特质有关。分裂型特质也可能调节认知能力，因为它与健康受试者的注意力缺陷有关。在这项研究中，我们检验了以下假设：即已确定的遗传风险变异 ZNF804A rs1344706 和 CACNA1C rs1006737 与心理测量学分裂型特质有关，分裂型特质介导了它们对注意力的影响，或者反之亦然。在来自 FOR2107 队列研究的 615 名健康受试者中，我们分析了遗传风险变异 ZNF804A rs1344706 和 CACNA1C rs1006737、心理测量学分裂型特质（简短分裂型人格问卷 SPQB）和持续和选择性注意力的神经心理学测量（d2 测试）。ZNF804A rs1344706 的 C（非风险）等位基因与女性的 SPQ-B 认知知觉子量表的高分显著相关，与两性的注意力缺陷相关。这种分裂型特质维度也介导了 ZNF804A 对女性注意力的影响，但对男性没有影响。CACNA1C rs1006737-A 仅在男性中表现出与人际分裂型特质的显著性别调节负相关，对注意力没有影响。我们的多变量模型表明，两个精神病风险基因对分裂型特质的维度和部分注意力有不同的遗传贡献。这支持了一个共同的遗传影响模型，即分裂型特质和精神分裂症中受损的认知功能之间存在遗传影响。
