Abstract
Psychiatric disorders such as anxiety and depression precipitated by substance use occurred during both use and withdrawal. Exosomes play significant roles in biological functions and regulate numerous physiological and pathological processes in various diseases, in particular substance use disorders (SUDs) and other psychiatric disorders. To better understand the role of exosomal miRNAs in the pathology of symptoms of anxiety and depression in patients with SUDs, we first isolated circulating exosomes from heroin-dependent patients (HDPs) and methamphetamine-dependent patients (MDPs) and identified exosomal miRNAs that were differentially expressed between patients and healthy controls (HCs). Furthermore, the correlations between exosomal DE-miRNAs and symptoms of anxiety and depression which were measured using Hamilton-Anxiety (HAM-A)/Hamilton-Depression (HAM-D) Rating Scales in the participants. Notably, the expression level of exosomal hsa-miR-16-5p, hsa-miR-129-5p, hsa-miR-363-3p, and hsa-miR-92a-3p showed significantly negative correlations with HAM-A scores in both HDPs and MDPs. But all of the 4 DE-miRNAs lost significant correlations with HAM-D scores in HDPs. Functional annotation analyses showed that the target genes of the DE-miRNAs were mainly enriched for “synapse”, “cell adhesion”, “focal adhesion” and “MHC class II protein complex”. Our study suggests that a set of circulating exosomal miRNAs were associated with anxiety and depression in SUD patients and may have clinical utility as diagnostic and prognostic biomarkers.
Highlights
At least 35 million people suffer from substance use disorders (SUDs) globally[1], which has led to major social and health concerns
The results showed that target genes of the DE-miRNAs were mainly enriched in nervous system, cell mobility and proliferation, and immune system both in methamphetamine-dependent patients (MDPs) vs healthy controls (HCs) and heroin-dependent patients (HDPs) vs HCs
There are 16 DE-miRNAs were identified between MDPs and HDPs, but all these 16 miRNAs lost significant difference when adjusted by false-discovery rate (FDR)
Summary
At least 35 million people suffer from substance use disorders (SUDs) globally[1], which has led to major social and health concerns. Significant research efforts have been devoted to depression and anxiety through the use of neuroimaging, genetics, epigenetics, and blood-based approaches in an attempt to identify pathogenic- and treatment-related b iomarkers[16]. Changes in DNA17, epigenetic modifications (including DNA methylation and histone modifications)[18,19], and miRNA level[20] have all been used as biomarkers in neurological and psychiatric disorders. Neurotrophic factors such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF) have been investigated as potential biomarkers in psychiatric disorders, including SUDs21–24. Existing biomarkers in cerebrospinal fluid (CSF) [e.g., monoamine and cocaine- and amphetamine-regulated transcript (CART) peptide identify biomarkers for psychiatric d iagnosis]26 or positron emission tomography (PET) imaging [targeting serotonin transporter (5-HTT), 5-HTT and 5-HT1A, tau, neurofilament light, and neurogranin]27–29 are invasive or expensive, far from comprehensive, and often lack sensitivity and specificity
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