Multi-omics study reveals associations among neurotransmitter, extracellular vesicle-derived microRNA and psychiatric comorbidities during heroin and methamphetamine withdrawal

作者：Fengrong Chen, Xu Yu, Kai Shi, Zunyue Zhang, Zhenrong Xie, Hongjin Wu, Yuru Ma, Yong Zhou, Cheng Chen, Jiqing Yang, Yuan Wang, Trevor W. Robbins, Kunhua Wang, Juehua Yu · 发表于：Biomedicine & Pharmacotherapy · 年份：2022 · DOI：10.1016/j.biopha.2022.113685 · 被引用次数：25 · 研究领域：Extracellular vesicles in disease、Autophagy in Disease and Therapy、Tryptophan and brain disorders

Despite decades of research in the field of substance withdrawal, molecular biomarkers and related mechanistic study have generally been lacking. In addition to known neurotransmitters, circulating miRNAs are found in small vesicles known as exosomes within blood that have diagnostic potential and are known to contribute to psychiatric disorders. The aim of this work was to characterize the changes in neurotransmitter and exosomal miRNA profiles during heroin and methamphetamine withdrawal using a cross-sectional study design, and to determine their associations to psychiatric comorbidities in a large group of patients with substance use disorders (SUDs). Using weighted gene co-expression network analysis, a series of known, conserved, and novel exosomal miRNAs were identified as being associated with the severity of anxiety and depression, as well as the concentrations of neurotransmitters GABA, choline, and serotonin. Bioinformatics analyses established that the differences in the miRNA profile target signaling pathways are significantly associated with developmental and intellectual abnormalities. Notably, a set of dysregulated miRNA signatures including hsa-mia-451a and hsa-mir-21a resulted in an AUC of 0.966 and 0.861, respectively, for predicting the patients with SUDs. Furthermore, hsa-miR-744a-5p was positively correlated with serotonin, and its important role in maintaining neuronal development and function was revealed using an in vitro human induced pluripotent ste...