Prognostic plasma exosomal microRNA biomarkers in patients with substance use disorders presenting comorbid with anxiety and depression

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.

Integration of Molecular Inflammatory Interactome Analyses Reveals Dynamics of Circulating Cytokines and Extracellular Vesicle Long Non-Coding RNAs and mRNAs in Heroin Addicts During Acute and Protracted Withdrawal

“…To gain insight into the transcriptional dynamics of extracellular vesicles, we utilized the size exclusion chromatography approach to isolate exosomes derived from the peripheral blood of selected heroin addicts (n = 20) and HCs (n = 10) for RNA sequencing ( 27 ). Exosomes were characterized and verified using transmission electron microscopy, nanoparticle tracking analysis, and western blotting assays.…”

“…A clear history of heroin use and current medication was obtained via self-report and verified with caregivers and was noted in the medical record when possible. Samples were collected as previously described ( 27 ). For the heroin addicts during withdrawal, inclusion criteria were as follows: (1) diagnosed with heroin dependence and (2) age between 20 and 55 years.…”

“…Exosomes are membrane-bound extracellular vesicles, usually 40–100 nm in diameter, presenting in blood, urine, saliva, cerebral spinal fluid, and breast milk ( 26 ). We and others have previously shown that the exosomal miRNAs are involved in the development of psychiatric withdrawal symptoms in patients with SUDs ( 27 , 28 ), although the role of exosomal (Ex)-lncRNAs/mRNAs in SUDs remains undetermined. In addition, when evaluating the psychoneuroimmunologic factors involved in heroin addicts, there is a need to differentiate between the acute and protracted withdrawal (PW) stages.…”

Integration of molecular inflammatory interactome analyses reveals dynamics of circulating cytokines and extracellular vesicle long non-coding RNAs and mRNAs in heroin addicts during acute and protracted withdrawal

“…To gain insight into the transcriptional dynamics of extracellular vesicles, we utilized the size exclusion chromatography approach to isolate exosomes derived from the peripheral blood of selected heroin addicts (n = 20) and HCs (n = 10) for RNA sequencing. (27) Exosomes were characterized and verified using transmission electron microscopy, nanoparticle tracking analysis, and western blotting assays. CD63 and CD81 served as exosome surface markers, while Calnexin was used as a negative marker, and their expression patterns were verified by western blot results ( Supplementary Fig.…”

Dynamics of neurotransmitter and extracellular vesicle-derived microRNA landscapes during heroin and methamphetamine withdrawal

“…Although high-throughput sequencing has been attempted to explore the miRNA content in exosomes from patients with SUDs (Chen et al, 2021;Wang et al, 2019), the underlying molecular mechanisms of exosomal miRNAs in the regulation of withdrawal symptoms remains to be fully elucidated. In the present study, we aimed to profile neurotransmitter and exosomal miRNAs in plasma to identify a subset of neurotransmitter and exosomal miRNA biomarkers in a large group of patients with SUDs undergoing withdrawal.…”