Liu Song
Department of General Surgery, Nanjing Drum Tower Hospital, Nanjing, China.
Medical School of Nanjing University, Nanjing, China.
Front Psychiatry. 2020 Apr 16;11:269. doi: 10.3389/fpsyt.2020.00269. eCollection 2020.
Suicide is the most severe consequence of depression which has become a leading cause of disability and a global disease burden. Recent evidence indicates a central role of small molecules in the pathogenesis of depression and associated suicidal behaviors. However, there lacks a systemic exploration of small molecules in the development of depression-associated suicide, and it remains unclear how they affect an individual's behavior. In order to compare the metabonomic profiles between drug-naïve patients with depression-associated suicidal behaviors and healthy individuals, we conducted a systemic database search for studies of metabolic characteristics in depression-associated suicidal behavior. Manual data curation and statistical analysis and integration were performed in Excel. We further performed an enrichment analysis of signaling pathway prediction using the Reactome Pathway Analysis tool. We have identified 17 metabolites that expressed differently between drug-naïve patients with depression-associated suicidal behaviors and healthy controls. We have integrated these metabolites into biological signaling pathways and provided a visualized signaling network in depressed suicidal patients. We have revealed that "transport of small molecules", "disease", "metabolism" and "metabolism of proteins" were the most relevant signaling sections, among which "transport of inorganic cations/anions and amino acids/oligopeptides", "SLC-mediated transmembrane transport", and "metabolism of amino acids and derivatives" should be further studied to elucidate their potential pathogenic mechanism in the development of depression and associated suicidal behavior. In conclusion, our findings of these 17 metabolites and associated signaling pathways could provide an insight into the molecular pathogenesis of depression-associated suicidal behavior and potential targets for new drug inventions.
自杀是抑郁症最严重的后果，抑郁症已成为导致残疾的主要原因和全球疾病负担。最近的证据表明小分子在抑郁症及相关自杀行为的发病机制中起核心作用。然而，目前缺乏对抑郁症相关自杀发展过程中小分子的系统性探索，它们如何影响个体行为仍不清楚。为了比较未服用过药物的伴有自杀行为的抑郁症患者与健康个体之间的代谢组学特征，我们对抑郁症相关自杀行为的代谢特征研究进行了系统性数据库检索。在Excel中进行了手动数据整理、统计分析和整合。我们还使用Reactome通路分析工具对信号通路预测进行了富集分析。我们已经确定了17种在未服用过药物的伴有自杀行为的抑郁症患者和健康对照之间表达不同的代谢物。我们将这些代谢物整合到生物信号通路中，并为抑郁自杀患者提供了一个可视化的信号网络。我们发现“小分子转运”“疾病”“代谢”和“蛋白质代谢”是最相关的信号部分，其中“无机阳离子/阴离子和氨基酸/寡肽的转运”“溶质载体介导的跨膜转运”以及“氨基酸及其衍生物的代谢”应进一步研究，以阐明它们在抑郁症及相关自杀行为发展中的潜在致病机制。总之，我们对这17种代谢物及相关信号通路的研究结果可为抑郁症相关自杀行为的分子发病机制及新药研发的潜在靶点提供见解。
