Konjevod Marcela, Sáiz Jorge, Bordoy Lucía, Strac Dubravka Svob, Taha Ameer Y, Lanceros-Méndez Senentxu, Alonso Rosa M
Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000, Zagreb, Croatia.
FARMARTEM Group, Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940, Leioa, Biscay, Spain.
Mol Med. 2025 Jul 9;31(1):254. doi: 10.1186/s10020-025-01258-7.
Schizophrenia, major depressive disorder, bipolar disorder and posttraumatic stress disorder are severe and profoundly debilitating mental illnesses. Due to their heterogeneity and polygenic nature, the metabolic pathways and biological mechanisms underlying these conditions remain elusive. Consequently, diagnosing psychiatric disorders is a complex and multifaceted process, relying on clinical assessment and standardized diagnostic criteria. There is a growing demand to identify and integrate potential biomarkers for these disorders, especially for early diagnosis, to enhance diagnostic accuracy and complement existing diagnostic tools. Validating potential diagnostic biomarkers is essential to ensure their accuracy, reliability, generalizability, and clinical utility.In this article we provide a comprehensive review of validated metabolomics research, focusing on both the specific psychiatric conditions and the types of validation performed. Our scope is limited to peer-reviewed studies that include studies that performed validation studies in independent cohorts, cross-validation, or external validation. Due to the lack of published research, most of these validation studies have concentrated on major depressive disorder and schizophrenia, with fewer studies addressing bipolar disorder and posttraumatic stress disorder.Biomarkers are considered as validated if they demonstrated reproducibility in additional cohorts and biological relevance across independent datasets. However, several limitations must be acknowledged, including the heterogeneity in study design, small sample sizes, different analytical platforms, and inconsistent validation criteria across studies. Published results reveal that potential metabolomics biomarkers pertain to diverse categories pointing to a range of cellular, biological, and metabolic processes and emphasizing the intricate nature of psychiatric disorders. Such findings illustrate the formidable challenge of identifying and validating clinically useful metabolomic biomarkers and underscore the necessity for further research that encompasses various validation methodologies.
精神分裂症、重度抑郁症、双相情感障碍和创伤后应激障碍是严重且使人极度衰弱的精神疾病。由于这些疾病具有异质性和多基因性质，其潜在的代谢途径和生物学机制仍不清楚。因此，诊断精神疾病是一个复杂且多方面的过程，依赖于临床评估和标准化诊断标准。对于识别和整合这些疾病的潜在生物标志物的需求日益增长，尤其是用于早期诊断，以提高诊断准确性并补充现有的诊断工具。验证潜在的诊断生物标志物对于确保其准确性、可靠性、可推广性和临床实用性至关重要。在本文中，我们对已验证的代谢组学研究进行了全面综述，重点关注特定的精神疾病状况以及所进行的验证类型。我们的范围仅限于同行评审的研究，包括在独立队列中进行验证研究、交叉验证或外部验证的研究。由于缺乏已发表的研究，这些验证研究大多集中在重度抑郁症和精神分裂症，涉及双相情感障碍和创伤后应激障碍的研究较少。如果生物标志物在其他队列中具有可重复性且在独立数据集中具有生物学相关性，则被认为是经过验证的。然而，必须认识到几个局限性，包括研究设计的异质性、样本量小、不同的分析平台以及各研究之间不一致的验证标准。已发表的结果表明，潜在的代谢组学生物标志物涉及多种类别，指向一系列细胞、生物学和代谢过程，并强调了精神疾病的复杂性。这些发现说明了识别和验证临床有用的代谢组学生物标志物的巨大挑战，并强调了采用各种验证方法进行进一步研究的必要性。
