抗精神病药物与认知功能的新型蛋白-蛋白相互作用网络

K. Thanontip, B. Chetsawang, Vasunun Chumchua
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摘要

认知功能是心理过程的智力活动,如注意力、处理速度、学习和记忆、执行功能、语言流畅性和工作记忆。认知缺陷可能导致精神疾病的功能性残疾。因此,改善认知功能有可能提高生活质量和职业能力,减少疾病问题和社会成本。最近的证据强调,传统的抗精神病药物对治疗阳性症状有效,但对认知障碍几乎没有治疗效果,并产生不良的功能结果。据推测,抗精神病药物可能会导致认知障碍或精神疾病的下降。因此,本研究旨在阐明可能涉及抗精神病药物引起的认知障碍的蛋白质网络。GeneCards分析结果显示,精神分裂症常用抗精神病药物靶基因213个,与精神分裂症认知功能相关基因122个,与精神分裂症抗精神病药物和认知功能相关基因28个。通过蛋白质相互作用(PPI)网络分析和聚类方法,生成了12个相互作用显著的蛋白质的蛋白质相互作用网络。采用通路分组网络分析方法,鉴定出抗精神病药物与认知功能相关的16条重要通路。这些结果为发现抗精神病药物可能在精神分裂症认知缺陷中起关键作用的新靶点提供了线索证据。
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Novel Protein-Protein Interaction Network of Antipsychotic Drugs and Cognitive Function
Cognitive function is the intellectual activity of mental processes, such as, attention, processing speed, learning and memory, executive function, verbal fluency, and working memory. Cognitive deficits may contribute to functional disability in psychiatric disorders. Therefore, improving cognitive function has the potential to enhance the quality of life and occupational capacity, and reduce disease problems and societal costs. Recent evidence emphasized that conventional antipsychotics effective in treating positive symptoms but have almost no therapeutic benefit on cognitive impairment and produce a poor functional outcome. It has been hypothesized that antipsychotics might induce cognitive impairment or decline in psychiatric disorders. Therefore, this study aims to elucidate the network of proteins that may involve in antipsychotic drug-induced cognitive impairment. The results of GeneCards analysis showed 213 target genes of commonly use antipsychotics in schizophrenia, 122 genes associated with cognitive function in schizophrenia, and 28 genes related to antipsychotics and cognitive function in schizophrenia. Protein-protein interaction (PPI) network of 12 significantly interconnected proteins was generated by the PPI network analysis and clustering method. The 16 significant pathways related to antipsychotic drugs and cognitive function were identified using pathway grouped network analysis. These results demonstrate clue evidence to discover novel target sites of action of antipsychotics that might play a pivotal role in cognitive deficits in schizophrenia.
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