Jagannath Vinita, Theodoridou Anastasia, Gerstenberg Miriam, Franscini Maurizia, Heekeren Karsten, Correll Christoph U, Rössler Wulf, Grünblatt Edna, Walitza Susanne
Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Zurich, Switzerland.
Front Psychiatry. 2017 Dec 20;8:292. doi: 10.3389/fpsyt.2017.00292. eCollection 2017.
Schizophrenia is characterized by positive and negative symptoms and cognitive dysfunction. The glutamate hypothesis of schizophrenia has been hypothesized to explain the negative symptoms and cognitive deficits better than the dopamine hypothesis alone. Therefore, we aimed to evaluate whether glutamatergic variants such as d-amino acid oxidase (), DAO activator ()/, and neuregulin 1 () single-nucleotide polymorphisms (SNPs) and their mRNA levels predicted (i) transition to schizophrenia spectrum disorders and (ii) research domain criteria (RDoC) domains, mainly negative valence and cognitive systems. In a 3-year prospective study cohort of 185 individuals (age: 13-35 years) at high risk and ultra-high risk (UHR) for psychosis, we assessed (rs3918347, rs4623951), (rs778293, rs3916971, rs746187), and (rs10503929) SNPs and their mRNA expression. Furthermore, we investigated their association with RDoC domains, mainly negative valence (e.g., anxiety, hopelessness) and cognitive (e.g., perception disturbances, disorganized symptoms) systems. rs10503929 CC + CT versus TT genotype carriers experienced significantly more disorganized symptoms. rs746187 CC versus CT + TT genotype, rs3916971 TT versus TC + CC genotype, and rs3918347 GA + AA versus GG genotype carriers experienced nominally more hopelessness, visual perception disturbances, and auditory perception disturbances, respectively. The schizophrenia risk G-allele of rs3918347 nominally increased risk for those UHR individuals with attenuated positive symptoms syndrome. No association between SNPs, and conversion to schizophrenia spectrum disorders was observed. Our findings suggest that , and polymorphisms might influence both RDoC negative valence and cognitive systems, but not transition to schizophrenia spectrum disorders.
精神分裂症的特征为阳性症状、阴性症状及认知功能障碍。相较于单纯的多巴胺假说，精神分裂症的谷氨酸假说被认为能更好地解释阴性症状和认知缺陷。因此，我们旨在评估诸如D-氨基酸氧化酶（DAO）、DAO激活剂（DAAO）/G72、神经调节蛋白1（NRG1）等谷氨酸能基因变异的单核苷酸多态性（SNP）及其mRNA水平是否能预测：（i）向精神分裂症谱系障碍的转变；（ii）主要为负性效价和认知系统的研究领域标准（RDoC）领域。在一项针对185名年龄在13 - 35岁的精神病高风险和超高风险（UHR）个体的3年前瞻性研究队列中，我们评估了DAO（rs3918347、rs4623951）、DAAO（rs778293、rs3916971、rs746187）和NRG1（rs10503929）的SNP及其mRNA表达。此外，我们研究了它们与RDoC领域的关联，主要是负性效价（如焦虑、绝望）和认知（如感知障碍、紊乱症状）系统。rs10503929的CC + CT基因型携带者与TT基因型携带者相比，经历了显著更多的紊乱症状。rs746187的CC基因型与CT + TT基因型相比，rs3916971的TT基因型与TC + CC基因型相比，以及rs3918347的GA + AA基因型与GG基因型携带者分别在绝望感、视觉感知障碍和听觉感知障碍方面有更高的发生率。rs3918347的精神分裂症风险G等位基因在那些具有亚临床阳性症状综合征的UHR个体中名义上增加了风险。未观察到DAAO SNP与向精神分裂症谱系障碍转变之间的关联。我们的研究结果表明，DAAO、DAO和NRG1多态性可能会影响RDoC负性效价和认知系统，但不会影响向精神分裂症谱系障碍的转变。
