REVIEW: Extracellular Vesicles as Potential Biomarkers in Addictive Disorders

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Vsevolod V. Severtsev^1,2,a*, Margarita A. Pavkina¹, Nikolay N. Ivanets¹, Maria A. Vinnikova^1,3, Alexander A. Yakovlev^4,5

¹Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, 119048 Moscow, Russia

²Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical-Biological Agency of the Russian Federation, 143007 Moscow, Russia

³Moscow Scientific and Practical Center of Narcology, Moscow Healthcare Department, 109390 Moscow, Russia

⁴Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia

⁵Research and Clinical Center for Neuropsychiatry, Moscow Healthcare Department, 115419 Moscow, Russia

^* To whom correspondence should be addressed.

Received: April 22, 2024; Revised: August 3, 2024; Accepted: August 9, 2024

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Small extracellular vesicles (sEVs) and their role in mental and addictive disorders are extremely promising research areas. Because of their small size, sEVs can pass through the blood–brain barrier. The membrane of sEVs contain proteins that protect them against destruction by the organism’s immune system. Due to these properties, sEVs circulating in the blood can be used as potential biomarkers of processes occurring in the brain. Exposure to psychoactive substances in vitro and in vivo affects sEV biogenesis and significantly alters the amount of sEVs and chemical composition of their cargo. Based on the published reports, sEVs carry numerous potential biomarkers of addictive pathologies, although the diagnostic significance of these markers still has to be evaluated. A large body of evidence indicates that psychoactive substances influence Rab family GTPases, Toll-like receptors, complement system components, and cytokines. In some studies, the effect of psychoactive substances on sEVs was found to be sex-dependent. It has become commonly accepted that sEVs are involved in the regulation of neuroinflammation and interaction between glial cells and neurons, as well as between peripheral cells and cells of the central nervous system. Here, we formulated a hypothesis on the existence of two mechanisms/stages involved in the effect of psychoactive substances on sEVs: the “fast” mechanism that provides neuroplasticity, and the “slow” one, resulting from the impaired biogenesis of sEVs and formation of aberrant vesicles.

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KEY WORDS: small extracellular vesicles, exosomes, biomarkers in psychiatry, addictology, fundamental mechanisms of addictive disorders, dependence syndrome

DOI: 10.1134/S0006297924110117

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