El-Ahmad Perla, Mendes-Silva Ana Paula, Diniz Breno S
UConn Center on Aging, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT, 06030, USA.
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
Mol Neurobiol. 2025 Mar;62(3):3462-3479. doi: 10.1007/s12035-024-04492-y. Epub 2024 Sep 19.
Psychiatric disorders are among the leading causes of disease burden worldwide. Despite their significant impact, their diagnosis remains challenging due to symptom heterogeneity, psychiatric comorbidity, and the lack of objective diagnostic tests and well-defined biomarkers. Leveraging genomic, epigenomic, and fragmentomic technologies, circulating cell-free DNA (ccfDNA)-based liquid biopsies have emerged as a potential non-invasive diagnosis and disease-monitoring tool. ccfDNA is a DNA species released into circulation from all types of cells through passive and active mechanisms and can serve as a biomarker for various diseases, namely, cancer. Despite their potential, the application of ccfDNA in neuropsychiatry remains underdeveloped. In this review, we provide an overview of liquid biopsies and their components, with a particular focus on ccfDNA. With a summary of pre-analytical practices and current ccfDNA technologies, we highlight the current state of research regarding the use of ccfDNA as a biomarker for neuropsychiatric disorders. Finally, we discuss future steps to unlock ccfDNA's potential in clinical practice.
精神疾病是全球疾病负担的主要原因之一。尽管其影响重大，但由于症状异质性、精神疾病共病以及缺乏客观诊断测试和明确的生物标志物，其诊断仍然具有挑战性。利用基因组学、表观基因组学和片段组学技术，基于循环游离DNA（ccfDNA）的液体活检已成为一种潜在的非侵入性诊断和疾病监测工具。ccfDNA是一种通过被动和主动机制从所有类型细胞释放到循环中的DNA，可作为各种疾病（即癌症）的生物标志物。尽管具有潜力，但ccfDNA在神经精神病学中的应用仍不发达。在这篇综述中，我们概述了液体活检及其组成部分，特别关注ccfDNA。通过总结分析前的操作和当前的ccfDNA技术，我们强调了将ccfDNA用作神经精神疾病生物标志物的研究现状。最后，我们讨论了释放ccfDNA在临床实践中潜力的未来步骤。
