Abstract

ObjectiveStimulant use instigates abstinence syndrome in humans. miRNAs are a critical component for the pathophysiology of stimulant abstinence. Here we sought to identify a miRNA marker of methamphetamine abstinence in the circulating extracellular vesicles (cEVs).MethodsmiR-137 in the cEVs was quantified by qPCR in thirty-seven patients under methamphetamine abstinence and thirty-five age-matched healthy controls recruited from 2014 to 2016 from the general adult population in a hospital setting, Seoul, South Korea. Diagnostic power was evaluated by area under curve in the receiver-operating characteristics curve and other multiple statistical parameters.ResultsPatients under methamphetamine abstinence exhibited a significant reduction in cEV miR-137. Overall, cEV miR-137 had high potential as a blood-based marker of methamphetamine abstinence. cEV miR-137 retained the diagnostic power irrespective of the duration of methamphetamine abstinence or methamphetamine use. Interestingly, cEV miR-137 interacted with age: Control participants displayed an aging-dependent reduction of cEV miR-137, while methamphetamine-abstinent patients showed an aging-dependent increase in cEV miR-137. Accordingly, cEV miR-137 had variable diagnostic power depending on age, in which cEV miR-137 more effectively discriminated methamphetamine abstinence in the younger population. Duration of methamphetamine use or abstinence, cigarette smoking status, depressive disorder, or antidepressant treatment did not interact with the methamphetamine abstinence-induced reduction of cEV miR-137.ConclusionOur data collectively demonstrated that miR-137 in the circulating extracellular vesicles held high potential as a stable and accurate diagnostic marker of methamphetamine abstinence syndrome.

Highlights

  • Abstinence syndrome is a critical subdivision of substanceinduced disorders

  • We found that MA abstinence substantially reduces circulating extracellular vesicles (cEVs) miR-137 in human patients

  • We examined whether the patients undergoing MA abstinence exhibited altered expression of miR-137 in the cEV. qPCR analysis showed that cEV miR-137 was notably reduced in the MA-abstinent patients (Figure 1a)

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Summary

Introduction

Abstinence syndrome is a critical subdivision of substanceinduced disorders. Abstinence syndrome develops and persists for years after cessation of prolonged substance use (Cruickshank and Dyer 2009). Abstinence syndrome causes significant impairment in our daily lives, most notably within the social and occupational spheres (American Psychiatric Association 2013). The biological diagnosis of substance abstinence syndrome has been hampered by limitations of the current diagnostic method, the limited window of detection and controversial accuracy (Dolan et al 2004; Fiorentin et al 2018; Jarvis et al 2017; Taylor et al 2017). Methamphetamine (MA) is a white-colored, odorless, synthetic stimulant derived from substituting the amine group into methyl group in amphetamine.

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