Dynamic Characteristics and Application Prospects of Potential Addiction Biomarkers and Their Quantification Analysis of mRNA in Peripheral Blood Immunocyte
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1)Department of Psychology, Shaoxing University, Shaoxing 312000, China;2)MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi’an 710062, China;3)Shaanxi Provincial Drug Rehabilitation Administration, Xi’an 710003, China;4)Faculty of Education, Shaanxi Normal University, Xi’an 710062, China

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This work was supported by grants from the Humanities and Social Science Fund of Ministry of Education of China (24YJC190034), Natural Science Basic Research Program of Shaanxi (2024JC-YBQN-0225), The National Natural Science Foundation of China (11727813, 32471114), General Project of the 14th Five-Year Plan for Education Science of Shaanxi Province in 2023 (SGH23Y2258), the Advantage Education and Rehabilitation Programme for Drug Addiction from Ministry of Justice ([2023] No. 21), and the Special Support Program for Innovation Teams Led by High-level SanQin Talents of Shaanxi Province.

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    Abstract:

    Drug addiction is a worldwide issue that threaten social stability and development. It has been proved to be a chronic, relapsing disease that results from the prolonged effects of drugs on the various neural networks. Over time, plenty of attention has been paid to find new approaches to enhance the sensitivity and accuracy of assessment on addiction. In recent years, researchers found that the expression of neurotransmitters and their receptors in some peripheral blood immunocyte may reflect their expression in the brain. By analyzing the changes of addiction-related neural biomarkers in peripheral blood immunocyte, it is potential to enhance the accuracy and the susceptibility of assessments on addiction and treatment effectiveness, and in turn help to reduce drug relapse. In this review, we summarize the potential biomarkers related to addiction in peripheral blood immunocyte and changing trend of their mRNA expression level in patients using different types of drugs and with different addiction states, and discuss their application prospects and future research directions. Previous studies have found various types of potential addiction biomarkers, including neurotransmitter receptor proteins, hormones, small molecule metabolites, ΔFosB microRNA and other transcriptional (post) regulators. Considering the correlation with addiction and the richness of existing research, this article mainly introduces neurotransmitter receptor proteins closely related to addiction, including dopamine receptors, opioid receptors, cannabinoid receptors, and N-methyl-D-aspartate (NMDA) receptors. The expression levels of these potential biomarkers often change correspondingly at different stages. For example, mRNA expression of dopamine D3 receptor was increased in opioid addicted and methadone-maintained patients, but no change was observed in the heroin abstinent group. In addition, changing patterns of the biomarkers induced by different types of drugs were also various. Although both opioid addiction and alcohol addiction could induce the change of mRNA expression of dopamine D4 receptor, it was decreased in the opioid addiction patients while increased in the alcohol addiction patients. On the basis of the available evidence, dopamine receptors (especially D4 receptors) are most potent at the indicative action across drugs and stages, while cannabinoid receptors mainly specifically reflect different stages of cannabis addiction status. In addition, the mRNA level of the GluN3B subunit showed a steady increase in different stages of opioid addiction and showed a decreased response to methadone treatment, suggesting that it has high potential as a biomarker of heroin addiction. Besides, the mRNA level of D4 receptor showed a clear reverse trend in the stage of alcohol addiction and alcohol withdrawal, which also reflected the potential of D4 receptor mRNA in the state of alcohol addiction. Considering evidences about serum levels changing in patients with drug addiction, immune response induced by drugs may be one possible mechanism of changes in the expression levels of transmitter receptors in the peripheral blood of drug addiction patients. Finally, the current research on biomarkers in peripheral blood for addiction is still relatively fragmented, and lack systematic mechanism exploration. Future studies could further combine animal studies and clinical studies to systematically demonstrate the role of relevant biomarkers and underlying mechanisms. In addition, there are often interactions between multiple biomarker proteins in mediating drug addiction, especially in the process of addiction development. Thus, the overall observation of the dynamic changing of different biomarkers in the addiction process may be helpful to enhance the accuracy of assessment of addiction states. At the same time, when applying peripheral blood biomarkers, corresponding standards should be formulated based on experimental evidences, so as to enhance the pertinence and effectiveness of peripheral blood biomarkers in the diagnosis and treatment of addiction.

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WU Mei-Lin, WANG Yi-Fan, DUAN Wen-Jing, DANG Wang-Jie, HAN Jing, REN Wei, DUAN Hai-Jun. Dynamic Characteristics and Application Prospects of Potential Addiction Biomarkers and Their Quantification Analysis of mRNA in Peripheral Blood Immunocyte[J]. Progress in Biochemistry and Biophysics,2025,52(3):603-614

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History
  • Received:December 25,2023
  • Revised:January 22,2025
  • Accepted:October 25,2024
  • Online: October 25,2024
  • Published: March 28,2025