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Biomolecules
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Translational Biomarkers in Addictive Disorders
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Translational Biomarkers in Addictive Disorders

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 23002

Special Issue Editors

Prof. Dr. Jorge Manzanares

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Guest Editor
Instituto de Neurociencias, Universidad Miguel Hernandez-CSIC, 03550 San Juan de Alicante, Spain
Interests: endocannabinoid system; psychiatry; animal models; alcohol addiction; cannabis use disorders
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. María S. García Gutiérrez

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Guest Editor
Instituto de Neurociencias, Miguel Hernández University, Av. Ramón y Cajal s/n, 03550 San Juan de Alicante, Alicante, Spain
Interests: cannabinoid receptors; psychiatry; neuroglia; animal models; neuropharmacology
Special Issues, Collections and Topics in MDPI journals
Dr. Francisco Navarrete

E-Mail Website
Guest Editor
Instituto de Neurociencias, Miguel Hernández University, Av. Ramón y Cajal s/n, San Juan de Alicante, 03550 Alicante, Spain
Interests: cannabinoids; addiction; psychiatry; neurology; translational research; molecular biology; neuropsychopharmacology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Addictive disorders are chronic and relapsing clinical conditions that produce a dramatic health burden worldwide. These are characterized by compulsive drug use and seeking, loss of control over drug consumption, and repeated relapse in drug use even after long periods of abstinence. Despite the range of the psychosocial and pharmacological therapeutic approaches for the treatment of substance use, relapse prevalence of drug consumption is estimated to be between 40% and 75%. This high rate of recurrence is largely due to the reduced efficacy of the available drugs or lack of specific treatments. Thus, there is a growing need to significantly improve our knowledge about the underlying mechanisms involved in the development of drug dependence. In this sense, the search of biomarkers is essential to achieve a more effective diagnostic classification of patients and to design new pharmacological tools with higher efficacy and safety.

This Special Issue focuses on the identification of biomarkers in drug addiction from a translational point of view, gathering preclinical and clinical information. Original reports or reviews providing new insights into potential diagnostic, monitoring, pharmacodynamic/response, predictive, prognostic, or susceptibility/risk biomarkers are welcome.

Prof. Dr. Jorge Manzanares
Prof. Dr. María S. García Gutiérrez
Prof. Dr. Francisco Navarrete
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • addiction
  • biomarker
  • translational
  • diagnosis
  • therapy

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Published Papers (6 papers)

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Research

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16 pages, 8033 KiB  
Article
Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation
by Hilal A. Rather, Shalini Mishra, Yixin Su, Ashish Kumar, Sangeeta Singh, Biswapriya B. Misra, Jingyun Lee, Cristina M. Furdui, Lindsey R. Hamilton, Robert W. Gould, Susan H. Nader, Michael A. Nader and Gagan Deep
Biomolecules 2022, 12(4), 510; https://doi.org/10.3390/biom12040510 - 28 Mar 2022
Cited by 5 | Viewed by 3050
Abstract
Cocaine use disorder has been reported to cause transgenerational effects. However, due to the lack of standardized biomarkers, the effects of cocaine use during pregnancy on postnatal development and long-term neurobiological and behavioral outcomes have not been investigated thoroughly. Therefore, in this study, [...] Read more.
Cocaine use disorder has been reported to cause transgenerational effects. However, due to the lack of standardized biomarkers, the effects of cocaine use during pregnancy on postnatal development and long-term neurobiological and behavioral outcomes have not been investigated thoroughly. Therefore, in this study, we examined extracellular vesicles (EVs) in adult (~12 years old) female and male rhesus monkeys prenatally exposed to cocaine (n = 11) and controls (n = 9). EVs were isolated from the cerebrospinal fluid (CSF) and characterized for the surface expression of specific tetraspanins, concentration (particles/mL), size distribution, and cargo proteins by mass spectrometry (MS). Transmission electron microscopy following immunogold labeling for tetraspanins (CD63, CD9, and CD81) confirmed the successful isolation of EVs. Nanoparticle tracking analyses showed that the majority of the particles were <200 nm in size, suggesting an enrichment for small EVs (sEV). Interestingly, the prenatally cocaine-exposed group showed ~54% less EV concentration in CSF compared to the control group. For each group, MS analyses identified a number of proteins loaded in CSF-EVs, many of which are commonly listed in the ExoCarta database. Ingenuity pathway analysis (IPA) demonstrated the association of cargo EV proteins with canonical pathways, diseases and disorders, upstream regulators, and top enriched network. Lastly, significantly altered proteins between groups were similarly characterized by IPA, suggesting that prenatal cocaine exposure could be potentially associated with long-term neuroinflammation and risk for neurodegenerative diseases. Overall, these results indicate that CSF-EVs could potentially serve as biomarkers to assess the transgenerational adverse effects due to prenatal cocaine exposure. Full article
(This article belongs to the Special Issue Translational Biomarkers in Addictive Disorders)
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16 pages, 1480 KiB  
Article
Changes in Serum N-Glycome for Risk Drinkers: A Comparison with Standard Markers for Alcohol Abuse in Men and Women
by Róisín O’Flaherty, Ádám Simon, Manuela Alonso-Sampedro, Sonia Sánchez-Batán, Carmen Fernández-Merino, Francisco Gude, Radka Saldova and Arturo González-Quintela
Biomolecules 2022, 12(2), 241; https://doi.org/10.3390/biom12020241 - 1 Feb 2022
Cited by 4 | Viewed by 2864
Abstract
Background and aim: Glycomic alterations serve as biomarker tools for different diseases. The present study aims to evaluate the diagnostic capability of serum N-glycosylation to identify alcohol risk drinking in comparison with standard markers. Methods: We included 1516 adult individuals [...] Read more.
Background and aim: Glycomic alterations serve as biomarker tools for different diseases. The present study aims to evaluate the diagnostic capability of serum N-glycosylation to identify alcohol risk drinking in comparison with standard markers. Methods: We included 1516 adult individuals (age range 18–91 years; 55.3% women), randomly selected from a general population. A total of 143 (21.0%) men and 50 (5.9%) women were classified as risk drinkers after quantification of daily alcohol consumption and the Alcohol Use Disorders Identification Test (AUDIT). Hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) was used for the quantification of 46 serum N-glycan peaks. Serum gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and red blood cell mean corpuscular volume (MCV) were measured by standard clinical laboratory methods. Results: Variations in serum N-glycome associated risk drinking were more prominent in men compared to women. A unique combination of N-glycan peaks selected by the selbal algorithm shows good discrimination between risk-drinkers and non-risk drinkers for men and women. Receiver operating characteristics (ROC) curves show accuracy for the diagnosis of risk drinking, which is comparable to that of the golden standards, GGT, MCV and CDT markers for men and women. Additionally, the inclusion of N-glycan peaks improves the diagnostic accuracy of the standard markers, although it remains relatively low, due to low sensitivity. For men, the area under the ROC curve using N-glycome data is 0.75, 0.76, and 0.77 when combined with GGT, MCV, and CDT, respectively. In women, the areas were 0.76, 0.73, and 0.73, respectively. Conclusion: Risk drinking is associated with significant variations in the serum N-glycome, which highlights its potential diagnostic utility. Full article
(This article belongs to the Special Issue Translational Biomarkers in Addictive Disorders)
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10 pages, 317 KiB  
Article
Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder
by João M. Castaldelli-Maia, André Malbergier, Adriana B. P. de Oliveira, Ricardo A. Amaral, André B. Negrão, Priscila D. Gonçalves, Antonio Ventriglio, Domenico de Berardis, Juliana de Antonio, Isabela Firigato, Gilka J. F. Gattás and Fernanda de Toledo Gonçalves
Biomolecules 2021, 11(10), 1495; https://doi.org/10.3390/biom11101495 - 10 Oct 2021
Cited by 5 | Viewed by 2735
Abstract
Background: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself [...] Read more.
Background: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study. Full article
(This article belongs to the Special Issue Translational Biomarkers in Addictive Disorders)

Review

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47 pages, 1031 KiB  
Review
Biomarkers of the Endocannabinoid System in Substance Use Disorders
by Francisco Navarrete, María S. García-Gutiérrez, Ani Gasparyan, Daniela Navarro, Francisco López-Picón, Álvaro Morcuende, Teresa Femenía and Jorge Manzanares
Biomolecules 2022, 12(3), 396; https://doi.org/10.3390/biom12030396 - 3 Mar 2022
Cited by 10 | Viewed by 4965
Abstract
Despite substance use disorders (SUD) being one of the leading causes of disability and mortality globally, available therapeutic approaches remain ineffective. The difficulty in accurately characterizing the neurobiological mechanisms involved with a purely qualitative diagnosis is an obstacle to improving the classification and [...] Read more.
Despite substance use disorders (SUD) being one of the leading causes of disability and mortality globally, available therapeutic approaches remain ineffective. The difficulty in accurately characterizing the neurobiological mechanisms involved with a purely qualitative diagnosis is an obstacle to improving the classification and treatment of SUD. In this regard, identifying central and peripheral biomarkers is essential to diagnosing the severity of drug dependence, monitoring therapeutic efficacy, predicting treatment response, and enhancing the development of safer and more effective pharmacological tools. In recent years, the crucial role that the endocannabinoid system (ECS) plays in regulating the reinforcing and motivational properties of drugs of abuse has been described. This has led to studies characterizing ECS alterations after exposure to various substances to identify biomarkers with potential diagnostic, prognostic, or therapeutic utility. This review aims to compile the primary evidence available from rodent and clinical studies on how the ECS components are modified in the context of different substance-related disorders, gathering data from genetic, molecular, functional, and neuroimaging experimental approaches. Finally, this report concludes that additional translational research is needed to further characterize the modifications of the ECS in the context of SUD, and their potential usefulness in the necessary search for biomarkers. Full article
(This article belongs to the Special Issue Translational Biomarkers in Addictive Disorders)
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34 pages, 464 KiB  
Review
Inflammatory Biomarkers in Addictive Disorders
by Alvaro Morcuende, Francisco Navarrete, Elena Nieto, Jorge Manzanares and Teresa Femenía
Biomolecules 2021, 11(12), 1824; https://doi.org/10.3390/biom11121824 - 3 Dec 2021
Cited by 22 | Viewed by 5034
Abstract
Substance use disorders are a group of diseases that are associated with social, professional, and family impairment and that represent a high socio-economic impact on the health systems of countries around the world. These disorders present a very complex diagnosis and treatment regimen [...] Read more.
Substance use disorders are a group of diseases that are associated with social, professional, and family impairment and that represent a high socio-economic impact on the health systems of countries around the world. These disorders present a very complex diagnosis and treatment regimen due to the lack of suitable biomarkers supporting the correct diagnosis and classification and the difficulty of selecting effective therapies. Over the last few years, several studies have pointed out that these addictive disorders are associated with systemic and central nervous system inflammation, which could play a relevant role in the onset and progression of these diseases. Therefore, identifying different immune system components as biomarkers of such addictive disorders could be a crucial step to promote appropriate diagnosis and treatment. Thus, this work aims to provide an overview of the immune system alterations that may be biomarkers of various addictive disorders. Full article
(This article belongs to the Special Issue Translational Biomarkers in Addictive Disorders)
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18 pages, 1424 KiB  
Review
CB2 Receptor Involvement in the Treatment of Substance Use Disorders
by Francisco Navarrete, María S. García-Gutiérrez, Ani Gasparyan, Daniela Navarro and Jorge Manzanares
Biomolecules 2021, 11(11), 1556; https://doi.org/10.3390/biom11111556 - 20 Oct 2021
Cited by 14 | Viewed by 2946
Abstract
The pharmacological modulation of the cannabinoid receptor 2 (CB2r) has emerged as a promising potential therapeutic option in addiction. The purpose of this review was to determine the functional involvement of CB2r in the effects produced by drugs of abuse at the central [...] Read more.
The pharmacological modulation of the cannabinoid receptor 2 (CB2r) has emerged as a promising potential therapeutic option in addiction. The purpose of this review was to determine the functional involvement of CB2r in the effects produced by drugs of abuse at the central nervous system (CNS) level by assessing evidence from preclinical and clinical studies. In rodents, several reports suggest the functional involvement of CB2r in the effects produced by drugs of abuse such as alcohol, cocaine, or nicotine. In addition, the discovery of CB2r in brain areas that are part of the reward system supports the relevance of CB2r in the field of addiction. Interestingly, animal studies support that the CB2r regulates anxiety and depression behavioral traits. Due to its frequent comorbidity with neuropsychiatric disorders, these pharmacological actions may be of great interest in managing SUD. Preliminary clinical trials are focused on exploring the therapeutic potential of modulating CB2r in treating addictive disorders. These promising results support the development of new pharmacological tools regulating the CB2r that may help to increase the therapeutic success in the management of SUD. Full article
(This article belongs to the Special Issue Translational Biomarkers in Addictive Disorders)
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