D-amino acid oxidase activator (DAOA) gene, which plays a crucial role in the process of glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. We aimed to investigate whether the variation of DAOA rs2391191 is associated with alterations in white matter integrity of first-episode schizophrenia (FES) patients; and whether it influences the association between white matter integrity, cognitive function and clinical symptoms of schizophrenia. Forty-six patients with FES and forty-nine healthy controls underwent DTI and were genotyped for DAOA rs2391191. Psychopathological assessments were performed by Brief Psychiatric Rating Scale (BPRS) and Scale for Assessment of Negative Symptoms (SANS). Cognitive function was assessed by MATRICS Consensus Cognitive Battery (MCCB). Schizophrenia patients presented lower fractional anisotropy (FA) and higher radial diffusivity (RD), mainly spreading over the corpus callosum and corona radiata compared with healthy controls. Compared with patients carrying G allele, patients with AA showed lower FA in the body of corpus callosum, and higher RD in the genu of corpus callosum, right superior and anterior corona radiata, and left posterior corona radiata. In patients carrying G allele, FA in body of corpus callosum was positively correlated with working memory, RD in genu of corpus callosum was negatively associated with the speed of processing, working memory, and the composite score of MCCB, while no significant correlations were found in AA homozygotes. In our study, patients with FES presented abnormal white matter integrity in corpus callosum and corona radiata. Furthermore, this abnormality was associated with the genetic variation of DAOA rs2391191, with AA homozygotes showing less white matter integrity in the corpus callosum. Our findings possibly provide further support to the evidence that DAOA regulates the process of glutamatergic neurotransmission and mitochondrial function in the pathophysiological mechanism of schizophrenia.

D-氨基酸氧化酶激活因子 (DAOA) 基因在谷氨酸能传递和线粒体功能过程中起关键作用，经常与精神分裂症的易感性有关。我们旨在调查 DAOA rs2391191 的变异是否与首发精神分裂症 (FES) 患者白质完整性的改变有关；以及它是否影响白质完整性、认知功能和精神分裂症临床症状之间的关联。46 名 FES 患者和 49 名健康对照者接受了 DTI，并对 DAOA rs2391191 进行基因分型。通过简要精神病评定量表（BPRS）和阴性症状评估量表（SANS）进行精神病理学评估。通过 MATRICS 共识认知电池 (MCCB) 评估认知功能。与健康对照组相比，精神分裂症患者表现出较低的分数各向异性 (FA) 和较高的径向扩散率 (RD)，主要分布在胼胝体和放射冠上。与携带G等位基因的患者相比，AA患者胼胝体体FA较低，胼胝体膝部、右上放射冠、前放射冠、左后放射冠RD较高。在携带G等位基因的患者中，胼胝体FA与工作记忆呈正相关，胼胝体膝部RD与加工速度、工作记忆、MCCB综合评分呈负相关，但无显着相关性。在 AA 纯合子中。在我们的研究中，FES 患者在胼胝体和放射冠中表现出异常的白质完整性。此外，这种异常与 DAOA rs2391191 的遗传变异有关，AA 纯合子在胼胝体中显示出较少的白质完整性。我们的研究结果可能进一步支持DAOA在精神分裂症的病理生理机制中调节谷氨酸能神经传递和线粒体功能的证据。