Metabolomics reveals biomarkers of opioid use disorder

Reza Ghanbari,Jonathan D Pollock,Behrouz Abaei,Susan Mcritchie,Reza Malekzadeh,Arash Etemadi,Yuanyuan Li,Afarin Rahimi-Movaghar,Hossein Poustchi,Wimal Pathmasiri,Masoumeh Amin-Esmaeili,Gholamreza Roshandel,Susan C J Sumner,Amaneh Shayanrad

doi:10.1038/s41398-021-01228-7

Abstract

Opioid use disorder (OUD) is diagnosed using the qualitative criteria defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Diagnostic biomarkers for OUD do not currently exist. Our study focused on developing objective biological markers to differentiate chronic opiate users with OUD from chronic opiate users without OUD. Using biospecimens from the Golestan Cohort Study, we compared the metabolomics profiles of high opium users who were diagnosed as OUD positive with high opium users who were diagnosed as OUD negative. High opium use was defined as maximum weekly opium usage greater than or equal to the median usage (2.4 g per week), and OUD was defined as having 2 or more DSM-5 criteria in any 12-month period. Among the 218 high opium users in this study, 80 were diagnosed as OUD negative, while 138 were diagnosed as OUD positive. Seven hundred and twelve peaks differentiated high opium users diagnosed as OUD positive from high opium users diagnosed as OUD negative. Stepwise logistic regression modeling of subject characteristics data together with the 712 differentiating peaks revealed a signature that is 95% predictive of an OUD positive diagnosis, a significant (p < 0.0001) improvement over a 63% accurate prediction based on subject characteristic data for these samples. These results suggest that a metabolic profile can be used to predict an OUD positive diagnosis.

Highlights

More than fifty years have passed since Dole and Nyswander described opioid addiction as a metabolic disease, suggesting that opioids disrupt homeostasis to produce drug-seeking behavior in the face of adverse consequences[1]
We investigated urinary metabolomic profiles to reveal biomarkers that could differentiate high opium users who were diagnosed as Opioid Use Disorder (OUD) positive from high opium users who were diagnosed as OUD negative
With and without subject characteristics as potential covariates, using: (a) 712 peaks which differentiated high opium users who were diagnosed as OUD positive from high opium users who were diagnosed as OUD negative

Summary

Introduction

More than fifty years have passed since Dole and Nyswander described opioid addiction as a metabolic disease, suggesting that opioids disrupt homeostasis to produce drug-seeking behavior in the face of adverse consequences[1]. An important issue in the addiction is that people exposed to opioids may develop dependence, but not Opioid Use Disorder (OUD)[2]. OUD is a chronic recurrent disorder that increasingly causes undesirable emotional states by involving the brain’s reward system and could include impaired social functioning[3,4]. Despite significant advances in the genetics and neurobiology of addiction as a brain disease, and preliminary studies to discover biomarkers of OUD, validated systemic biomarkers for OUD do not exist[5]. Differential diagnosis of OUD is obtained through interview or questionnaire to determine if the patients meet the DSM-5 diagnostic criteria. These criteria include impaired control, social impairment, risky use, tolerance, withdrawal, craving, and continued use despite problems. Having at least two of the 11 criteria meets the diagnoses of OUD with the number of criteria met as an indicator of the severity of the OUD6

Methods

Results

Conclusion