Jia Rufei, Yuan Xiuxia, Zhang Xiaoyun, Song Peilun, Han Shaoqiang, Wang Shuying, Li Yajun, Zhang Siwei, Zhao Xinyi, Zhang Yu, Cheng Jingliang, Song Xueqin
Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Biological Psychiatry International Joint Laboratory of Henan, Zhengzhou University, Zhengzhou, China.
Front Neurosci. 2023 Apr 17;17:1153439. doi: 10.3389/fnins.2023.1153439. eCollection 2023.
The aim of the present study was to explore influencing factors of cognitive impairments and their interrelationships in drug-naïve, first-episode schizophrenia (SCZ).
Patients with drug naïve, first episode SCZ and healthy controls (HCs) were enrolled. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Serum levels of oxidative stress indices, including folate, superoxide dismutase (SOD), uric acid (UA) and homocysteine (Hcy), were determined after an overnight fast. Hippocampal subfield volumes were measured using FreeSurfer. Mediation models were conducted using the SPSS PROCESS v3.4 macro. A false discovery rate (FDR) correction was applied for multiple comparisons.
Sixty-seven patients with SCZ and 65 HCs were enrolled in our study. The patient group had significantly lower serum levels of folate and SOD and higher serum levels of HCY compared with the HCs (all < 0.05). The patient group had a significantly smaller volume of the whole hippocampus than the HC group ( < 0.05). We also found significant volume differences between the two groups in the following subfields: CA1, molecular layer, GC-ML-DG and fimbria (all < 0.05, uncorrected). The partial correlation analysis controlling for age and sex showed that the fimbria volume in the patient group was significantly positively associated with NAB scores ( = 0.382, pFDR = 0.024); serum levels of SOD in the patient group showed a significantly positive correlation with fimbria volume ( = 0.360, pFDR = 0.036). Mediation analyses controlling for age and sex showed that the serum levels of SOD in patients with SCZ had significant indirect effects on the NAB scores which were mediated by the fimbria volume [indirect effect = 0.0565, 95% CI from the bootstrap test excluding zero (0.0066 to 0.0891)].
Oxidative stress, a reduction in hippocampal subfield volumes and cognitive impairments occur in early SCZ. Oxidative stress impairs cognitive function by affecting hippocampal subfield volumes.
本研究旨在探讨初发未用药精神分裂症（SCZ）认知障碍的影响因素及其相互关系。
纳入初发未用药的SCZ患者和健康对照（HCs）。采用精神分裂症认知功能成套测验共识版（MCCB）评估认知功能。过夜禁食后测定血清氧化应激指标水平，包括叶酸、超氧化物歧化酶（SOD）、尿酸（UA）和同型半胱氨酸（Hcy）。使用FreeSurfer测量海马亚区体积。使用SPSS PROCESS v3.4宏程序进行中介模型分析。采用错误发现率（FDR）校正进行多重比较。
本研究纳入了67例SCZ患者和65例HCs。与HCs相比，患者组血清叶酸和SOD水平显著降低，血清HCY水平升高（均P<0.05）。患者组全海马体积显著小于HC组（P<0.05）。我们还发现两组在以下亚区存在显著的体积差异：CA1、分子层、颗粒细胞-分子层-齿状回和伞部（均P<0.05，未校正）。控制年龄和性别后的偏相关分析显示，患者组伞部体积与神经认知功能成套测验（NAB）得分显著正相关（r=0.382，P FDR=0.024）；患者组血清SOD水平与伞部体积显著正相关（r=0.360，P FDR=0.036）。控制年龄和性别的中介分析显示，SCZ患者血清SOD水平通过伞部体积对NAB得分有显著的间接效应[间接效应=0.0565，自抽样检验排除零的95%可信区间（0.0066至0.0891）]。
早期SCZ存在氧化应激、海马亚区体积减小和认知障碍。氧化应激通过影响海马亚区体积损害认知功能。
