Yuan Xiuxia, Li Xue, Pang Lijuan, Kang Yulin, Hei Gangrui, Zhang Xiaoyun, Zhang Peifen, Fan Xiaoduo, Song Xueqin
Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou, China.
BMC Psychiatry. 2025 May 22;25(1):524. doi: 10.1186/s12888-025-06965-3.
Cognitive impairments in patients with schizophrenia (SCZ) is associated with poor social functioning and long-term prognosis. Our previous work suggests that some key fungal markers including Purpureocillium, are linked to SCZ.
We present a case-control study that includes 136 first-episode, drug-naïve patients with SCZ and 92 healthy controls (HCs). Untargeted liquid chromatography/mass spectrometry (LC/MS) was utilized to measure serum metabolite levels. The abundance of Purpureocillium was assessed using the internal transcribed spacer (ITS) analysis. Cognitive function was measured using the MATRICS Consensus Cognitive Battery.
The present study demonstrated significant declines in attention and alertness (AV), speed of processing (SOP) in individuals with SCZ. The abundance of Purpureocillium was found to have a negative correlation with multiple domains of cognitive function. Additionally, SCZ-related metabolic markers 2-Oxoarginine, N-Acetyl-serotonin, Ergothioneine, Isobutyric acid and Biotin were significantly associated with both the abundance of Purpureocillium and cognitive scores (SOP and AV). Mediation analyses revealed that the abundance of Purpureocillium in patients with SCZ had significant direct and indirect effects on SOP and AV) through metabolic markers (2-Oxoarginine, N-Acetyl-serotonin, Ergothioneine). Further, Purpureocillium and the metabolic markers were found to be correlated with inflammation and oxidative stress, both of which have been associated with pathogenesis of SCZ.
Our findings suggest that Purpureocillium might be associated with cognitive impairments through its regulation on the metabolism of specific amino acids involved in inflammation and oxidative stress. A better understanding about the fungal-immune-metabolites association may lead to novel treatment approaches to improve cognitive function in patients with SCZ.
精神分裂症（SCZ）患者的认知障碍与社交功能差和长期预后不良有关。我们之前的研究表明，包括拟青霉属在内的一些关键真菌标志物与SCZ有关。
我们开展了一项病例对照研究，纳入136例首发、未用药的SCZ患者和92例健康对照（HCs）。采用非靶向液相色谱/质谱（LC/MS）法测定血清代谢物水平。使用内转录间隔区（ITS）分析评估拟青霉属的丰度。使用MATRICS共识认知成套测验评估认知功能。
本研究表明，SCZ患者的注意力和警觉性（AV）以及处理速度（SOP）显著下降。发现拟青霉属的丰度与认知功能的多个领域呈负相关。此外，与SCZ相关的代谢标志物2-氧代精氨酸、N-乙酰血清素、麦角硫因、异丁酸和生物素与拟青霉属的丰度以及认知评分（SOP和AV）均显著相关。中介分析显示，SCZ患者体内拟青霉属的丰度通过代谢标志物（2-氧代精氨酸、N-乙酰血清素、麦角硫因）对SOP和AV有显著的直接和间接影响。此外，发现拟青霉属和代谢标志物与炎症和氧化应激相关，而这两者均与SCZ的发病机制有关。
我们的研究结果表明，拟青霉属可能通过调节参与炎症和氧化应激的特定氨基酸的代谢与认知障碍有关。更好地理解真菌-免疫-代谢物之间的关联可能会带来改善SCZ患者认知功能的新治疗方法。
