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Sahu P, Verma HK, Bhaskar LVKS. Alcohol and alcoholism associated neurological disorders: Current updates in a global perspective and recent recommendations. World J Exp Med 2025; 15:100402. [PMID: 40115759 PMCID: PMC11718584 DOI: 10.5493/wjem.v15.i1.100402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 11/27/2024] [Accepted: 12/16/2024] [Indexed: 12/26/2024] Open
Abstract
Alcohol use disorder (AUD) is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social, occupational, or health consequences. AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a "severe problem". The central nervous system is the primary target of alcohol's adverse effects. It is crucial to identify various neurological disorders associated with AUD, including alcohol withdrawal syndrome, Wernicke-Korsakoff syndrome, Marchiafava-Bignami disease, dementia, and neuropathy. To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism. A comprehensive search of online databases, including PubMed, EMBASE, Web of Science, and Google Scholar, was conducted to identify relevant articles. Several neurotransmitters (dopamine, gamma-aminobutyric acid, serotonin, and glutamate) have been linked to alcoholism due to a brain imbalance. Alcoholism appears to be a complex genetic disorder, with variations in many genes influencing risk. Some of these genes have been identified, including two alcohol metabolism genes, alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene, which have the most potent known effects on the risk of alcoholism. Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage, nutrient deficiencies, and blood brain barrier dysfunction; however, the underlying mechanism is unknown. This review will provide a detailed overview of the neurobiology of alcohol addiction, followed by recent studies published in the genetics of alcohol addiction, molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.
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Affiliation(s)
- Prashanti Sahu
- Department of Zoology, GGU Bilaspur, Bilaspur 495009, Chhattīsgarh, India
| | - Henu Kumar Verma
- Department of Lung Health and Immunity, Helmholtz Zentrum Munich, Munich 85764, Bayren, Germany
| | - LVKS Bhaskar
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495001, Chhattīsgarh, India
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Tereshchenko SY, Afonicheva KV, Marchenko IV, Shubina MV, Smolnikova MV. Polymorphic variants of the dopamine receptor gene DRD2 (rs6277, rs1800497) in adolescents with problematic video game use. Vavilovskii Zhurnal Genet Selektsii 2024; 28:667-674. [PMID: 40200916 PMCID: PMC11975965 DOI: 10.18699/vjgb-24-74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 06/30/2024] [Accepted: 07/15/2024] [Indexed: 04/10/2025] Open
Abstract
Problematic video games use, as a specific form of problematic Internet use, is widespread among adolescents and can have negative effects on their mental and somatic well-being. An increasing incidence of addictive video gaming, as well as the overuse of the Internet, among the young population makes the current study of susceptibility factors, including the genetic component, relevant. There has been a number of investigations related to the involvement of gene variants of the neurotransmitter system in the development of Internet addiction, with the results being different for various ethnic groups. The dopamine type 2 receptor gene (DRD2) is one of the candidate genes for susceptibility to video game addiction. The aim of the work was to study polymorphic variants of the dopamine receptor gene DRD2 (rs6277, rs1800497) in Russian adolescents with problematic use of computer video games. A sampling of 407 adolescents aged 14.1 ± 1.8 years was tested, of which 56 (13.8 %) were identified as having problems with the pathological use of video games use based on the GASA scale results. Boys in the sample proved to be addicted to video games more than girls (p = 0.041). As a result of comparing the allele frequency of DRD2 (rs6277), a tendency to a higher frequency of the minor allele T was revealed in the group of adolescents with problematic video game use compared with adolescents without problematic video game use (i. e. 0.563 and 0.466, respectively, p = 0.06). When using the dominant inheritance model, it was revealed that adolescents with problematic use of video games were statistically significantly more likely to carry the T (CT+TT) allele (p = 0.04, OR = 2.14, CI = 1.01-4.53). The T allele DRD2 (rs6277) is associated with low expression of the dopamine receptor D2 and leads to decreasing the density and affinity of extrastriatal dopamine type 2 receptors, which is associated with impaired social communication as well. We suggest that the presence of CT and TT genotypes of rs6277 DRD2 may be a potential risk factor for developing problematic video game use in adolescents.
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Affiliation(s)
- S Yu Tereshchenko
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
| | - K V Afonicheva
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
| | - I V Marchenko
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
| | - M V Shubina
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
| | - M V Smolnikova
- Scientific Research Institute of Medical Problems of the North - a separate division of the Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia
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Davis S, Zhu J. Substance abuse and neurotransmission. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2022; 93:403-441. [PMID: 35341573 PMCID: PMC9759822 DOI: 10.1016/bs.apha.2021.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
The number of people who suffer from a substance abuse disorder has continued to rise over the last decade; particularly, the number of drug-related overdose deaths has sharply increased during the COVID-19 pandemic. Converging lines of clinical observations, supported by imaging and neuropsychological performance testing, have demonstrated that substance abuse-induced dysregulation of neurotransmissions in the brain is critical for development and expression of the addictive properties of abused substances. Recent scientific advances have allowed for better understanding of the neurobiological processes that mediates drugs of abuse and addiction. This chapter presents the past classic concepts and the recent advances in our knowledge about how cocaine, amphetamines, opioids, alcohol, and nicotine alter multiple neurotransmitter systems, which contribute to the behaviors associated with each drug. Additionally, we discuss the interactive effects of HIV-1 or COVID-19 and substance abuse on neurotransmission and neurobiological pathways. Finally, we introduce therapeutic strategies for development of pharmacotherapies for substance abuse disorders.
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Affiliation(s)
- Sarah Davis
- Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, United States
| | - Jun Zhu
- Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, United States.
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Fedorenko OY, Mikhalitskaya EV, Toshchakova VA, Loonen AJM, Bokhan NA, Ivanova SA. Association of PIP4K2A Polymorphisms with Alcohol Use Disorder. Genes (Basel) 2021; 12:genes12101642. [PMID: 34681036 PMCID: PMC8535504 DOI: 10.3390/genes12101642] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 10/17/2021] [Accepted: 10/17/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Alcohol use disorder (AUD) not only influences individuals and families but also has a lasting social impact on communities at the national level. Dopaminergic neurotransmission is involved in excessive alcohol consumption. Phosphatidylinositol-5-phosphate-4-kinase type 2 α (PIP4K2A) plays an important role in the regulation of ascending dopamine pathways. In this study; we determined possible associations between nine polymorphisms in PIP4K2A and AUD in Russian men. Methods: 279 Russian men with AUD were investigated. The control group consisted of 222 healthy men from the general Russian population. Genotyping of DNA samples for nine polymorphic variants of PIP4K2A was carried out by the Applied Biosystems™ QuantStudio™ 5 Real-Time PCR System with use of the TaqMan1 Validated SNP Genotyping Assay (Applied Biosystems; CIIIA). Results: Carriage of the PIP4K2A rs2230469*TT/T genotype/allele was a relative risk factor for developing AUD in men (p = 0.026 and p = 0.0084 accordingly). Moreover; men with AUD had a higher frequency of PIP4K2A rs746203*T allele (p = 0.023) compared to healthy men. Conclusions: For the first time; we demonstrated different PIP4K2A polymorphisms to be associated with AUD presumably due to dopamine system modulation resulting from regulation of the lateral habenula.
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Affiliation(s)
- Olga Yu. Fedorenko
- Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia; (E.V.M.); (V.A.T.); (N.A.B.); (S.A.I.)
- Division for Control and Diagnostics, School of Non-Destructive Testing and Security, National Research Tomsk Polytechnic University, 634050 Tomsk, Russia
- Correspondence:
| | - Ekaterina V. Mikhalitskaya
- Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia; (E.V.M.); (V.A.T.); (N.A.B.); (S.A.I.)
| | - Valentina A. Toshchakova
- Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia; (E.V.M.); (V.A.T.); (N.A.B.); (S.A.I.)
| | - Anton J. M. Loonen
- PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, 9713AV Groningen, The Netherlands;
| | - Nikolay A. Bokhan
- Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia; (E.V.M.); (V.A.T.); (N.A.B.); (S.A.I.)
- Department of Psychotherapy and Psychological Counseling, National Research Tomsk State University, 634050 Tomsk, Russia
- Department of Psychiatry, Addictology and Psychotherapy, Siberian State Medical University, 634050 Tomsk, Russia
| | - Svetlana A. Ivanova
- Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia; (E.V.M.); (V.A.T.); (N.A.B.); (S.A.I.)
- Division for Control and Diagnostics, School of Non-Destructive Testing and Security, National Research Tomsk Polytechnic University, 634050 Tomsk, Russia
- Department of Psychiatry, Addictology and Psychotherapy, Siberian State Medical University, 634050 Tomsk, Russia
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Boness CL, Watts AL, Moeller KN, Sher KJ. The Etiologic, Theory-Based, Ontogenetic Hierarchical Framework of Alcohol Use Disorder: A Translational Systematic Review of Reviews. Psychol Bull 2021; 147:1075-1123. [PMID: 35295672 PMCID: PMC8923643 DOI: 10.1037/bul0000333] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]
Abstract
Modern nosologies (e.g., ICD-11, DSM-5) for alcohol use disorder (AUD) and dependence prioritize reliability and clinical presentation over etiology, resulting in a diagnosis that is not always strongly grounded in basic theory and research. Within these nosologies, DSM-5 AUD is treated as a discrete, largely categorical, but graded, phenomenon, which results in additional challenges (e.g., significant phenotypic heterogeneity). Efforts to increase the compatibility between AUD diagnosis and modern conceptualizations of alcohol dependence, which describe it as dimensional and partially overlapping with other psychopathology (e.g., other substance use disorders) will inspire a stronger scientific framework and strengthen AUD's validity. We conducted a systematic review of 144 reviews to integrate addiction constructs and theories into a comprehensive framework with the aim of identifying fundamental mechanisms implicated in AUD. The product of this effort was the Etiologic, Theory-Based, Ontogenetic Hierarchical Framework (ETOH Framework) of AUD mechanisms, which outlines superdomains of cognitive control, reward, as well as negative valence and emotionality, each of which subsume narrower, hierarchically-organized components. We also outline opponent processes and self-awareness as key moderators of AUD mechanisms. In contrast with other frameworks, we recommend an increased conceptual role for negative valence and compulsion in AUD. The ETOH framework serves as a critical step towards conceptualizations of AUD as dimensional and heterogeneous. It has the potential to improve AUD assessment and aid in the development of evidence-based diagnostic measures that focus on key mechanisms in AUD, consequently facilitating treatment matching.
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Affiliation(s)
| | - Ashley L Watts
- Department of Psychological Science, University of Missouri
| | | | - Kenneth J Sher
- Department of Psychological Science, University of Missouri
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Park CI, Kim HW, Hwang SS, Kang JI, Kim SJ. Influence of dopamine-related genes on craving, impulsivity, and aggressiveness in Korean males with alcohol use disorder. Eur Arch Psychiatry Clin Neurosci 2021; 271:865-872. [PMID: 31559529 DOI: 10.1007/s00406-019-01072-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 09/19/2019] [Indexed: 12/22/2022]
Abstract
Dopamine is a major neuromodulator that is acutely involved in various cognitive processes, reward-motivated behaviors, and impulsivity. Abnormality in dopaminergic neurotransmission is implicated in the pathophysiology of alcohol use disorder (AUD). The present study examined the genetic influence of dopamine system on problematic drinking, impulsivity, and aggressiveness in a Korean male population with AUD. Five single nucleotide polymorphisms (SNPs) (rs4532 in DRD1, rs2283265 in DRD2, rs6280 in DRD3, rs1800497 in ANKK1, and rs4680 in COMT) and a variable number of tandem repeats (VNTRs) in DAT1 in 295 male patients with AUD were genotyped. For AUD-related clinical characteristics, the Alcohol Use Disorders Identification Test and the Obsessive-Compulsive Drinking Scale (OCDS) were used to assess the severity of hazardous drinking and craving symptoms, respectively. Participants also completed the UPPS-P Impulsive Behavior Scale (UPPS-P) and Buss-Perry Aggression Questionnaire (BPAQ). Analyses were performed using R package SNPassoc; statistical significance was set as p < 0.0083 after Bonferroni correction. A significant association was detected between DRD3 SNP rs6280 and OCDS scores. In regard to impulsivity and aggressiveness, rs4532 of DRD1 was significantly associated with UPPS-P score. Also, rs4532 demonstrated a nominally significant association with BPAQ score, although it did not reach statistical significance after correction for multiple comparisons. Results of this study support the idea that genetic variations in the dopamine system may contribute to alcohol cravings and impulsivity in patients with AUD.
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Affiliation(s)
- Chun Il Park
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Psychiatry, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Kim
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Medical Education, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Syung Shick Hwang
- Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jee In Kang
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Department of Psychiatry, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Se Joo Kim
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Department of Psychiatry, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Magistrelli L, Ferrari M, Furgiuele A, Milner AV, Contaldi E, Comi C, Cosentino M, Marino F. Polymorphisms of Dopamine Receptor Genes and Parkinson's Disease: Clinical Relevance and Future Perspectives. Int J Mol Sci 2021; 22:ijms22073781. [PMID: 33917417 PMCID: PMC8038729 DOI: 10.3390/ijms22073781] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/26/2021] [Accepted: 04/01/2021] [Indexed: 12/20/2022] Open
Abstract
Parkinson’s disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the midbrain. PD is clinically characterized by a variety of motor and nonmotor symptoms, and treatment relies on dopaminergic replacement. Beyond a common pathological hallmark, PD patients may present differences in both clinical progression and response to drug therapy that are partly affected by genetic factors. Despite extensive knowledge on genetic variability of dopaminergic receptors (DR), few studies have addressed their relevance as possible influencers of clinical heterogeneity in PD patients. In this review, we summarized available evidence regarding the role of genetic polymorphisms in DR as possible determinants of PD development, progression and treatment response. Moreover, we examined the role of DR in the modulation of peripheral immunity, in light of the emerging role of the peripheral immune system in PD pathophysiology. A better understanding of all these aspects represents an important step towards the development of precise and personalized disease-modifying therapies for PD.
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Affiliation(s)
- Luca Magistrelli
- PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, 21100 Varese, Italy; (L.M.); (A.F.)
- Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy; (A.V.M.); (E.C.)
| | - Marco Ferrari
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
| | - Alessia Furgiuele
- PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, 21100 Varese, Italy; (L.M.); (A.F.)
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
| | - Anna Vera Milner
- Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy; (A.V.M.); (E.C.)
| | - Elena Contaldi
- Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy; (A.V.M.); (E.C.)
- PhD Program in Medical Sciences and Biotechnology, University of Piemonte Orientale, 28100 Novara, Italy
| | - Cristoforo Comi
- Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy; (A.V.M.); (E.C.)
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
- Correspondence:
| | - Marco Cosentino
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
- Center of Research in Neuroscience, University of Insubria, 21100 Varese, Italy
| | - Franca Marino
- Centre of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy; (M.F.); (M.C.); (F.M.)
- Center of Research in Neuroscience, University of Insubria, 21100 Varese, Italy
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Barkley RA, Smith KM, Fischer M. ADHD risk genes involved in dopamine signaling and metabolism are associated with reduced estimated life expectancy at young adult follow-up in hyperactive and control children. Am J Med Genet B Neuropsychiatr Genet 2019; 180:175-185. [PMID: 30637915 DOI: 10.1002/ajmg.b.32711] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 12/08/2018] [Accepted: 12/10/2018] [Indexed: 12/20/2022]
Abstract
ADHD is associated with an elevated risk of mortality and reduced estimated life expectancy (ELE) by adulthood. Reduced life expectancy is substantially related to the trait of behavioral disinhibition; a correlate of both ADHD and of several dopamine genes related to dopamine signaling and metabolism. We therefore hypothesized that several ADHD risk genes related to dopamine might also be predictive of reduced ELE. Using a longitudinal study of 131 hyperactive children and 71 control cases followed to young adulthood, we examined whether several polymorphisms involving DRD4, DAT1, and DBH were related to ELE. The homozygous 9/9 allele of DAT1 and the heterozygous allele of DBH TaqI were associated with 5- and 2-year reductions, respectively, in total ELE. They did not operate on ELE through any relationships to ADHD specifically or behavioral disinhibition more generally. Instead, they showed links to alcohol use (DBH), reduced education, smoking, and reduced exercise (DAT1) employed in the computation of ELE. We conclude that polymorphisms of two dopamine genes are linked to reductions in ELE independently of their association with ADHD.
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Affiliation(s)
- Russell A Barkley
- This research was originally conducted at the Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Karen Müller Smith
- Department of Biology, University of Louisiana at Lafayette, Lafayette, Louisiana
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Celorrio D, Muñoz X, Amiano P, Dorronsoro M, Bujanda L, Sánchez MJ, Molina-Montes E, Navarro C, Chirlaque MD, MaríaHuerta J, Ardanaz E, Barricarte A, Rodriguez L, Duell EJ, Hijona E, Herreros-Villanueva M, Sala N, Alfonso-Sánchez MA, de Pancorbo MM. Influence of Dopaminergic System Genetic Variation and Lifestyle Factors on Excessive Alcohol Consumption. Alcohol Alcohol 2016; 51:258-267. [PMID: 26447226 DOI: 10.1093/alcalc/agv114] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 07/30/2015] [Indexed: 01/13/2023] Open
Abstract
AIMS To examine the role of genetic and environmental factors in the pathogenesis of alcohol dependence in a Spanish cohort of women and men. METHODS We analyzed the relationship between 56 genetic variants in 7 genes associated with the dopaminergic reward pathway and excessive alcohol consumption. The study sample (N = 1533, of which 746 were women) consisted of 653 heavy consumers and 880 very low consumers from the Spanish subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. Lifestyle variables were also examined to assess associations between genetic and environmental factors. RESULTS No statistically significant differences were found between cases and controls for the allele frequencies in five genes: TH, SLC18A2, DRD1, DRD3 and COMT. Conversely, some alleles of the 12 SNPs from the DRD2 locus and the 5 from the MAOA locus showed significant associations with excessive alcohol consumption. Namely, rs10891556 (DRD2) proved to be the only SNP positively correlated with excessive alcohol consumption in both sexes. DRD2 rs1800497 and rs877138 were significantly associated in men, whereas DRD2 rs17601612 and rs4936271 and MAOA rs5906898 were associated with excessive alcohol consumption in women. A correspondence analysis provided an overall lifestyle profile of excessive drinkers, who were predominantly men who smoked, had large intakes of meat, small intakes of fruit and vegetables, whose jobs did not require high education levels and who engaged in little physical activity. CONCLUSIONS It has shown the influence of dopaminergic pathway in the genetics of alcohol dependence with differences between men and women and providing a lifestyle profile of excessive drinkers.
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Affiliation(s)
- David Celorrio
- BIOMICs Research Group, 'Lucio Lascaray' Center for Research and Advanced Studies (CIEA), University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
| | - Xavier Muñoz
- Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain Unit of Nutrition, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain
| | - Pilar Amiano
- Public Health Division of Gipuzkoa, Department of Health of the Regional Government of the Basque Country, Donostia, Spain BIODonostia Research Institute, San Sebastián, Spain CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain
| | - Miren Dorronsoro
- Public Health Division of Gipuzkoa, Department of Health of the Regional Government of the Basque Country, Donostia, Spain BIODonostia Research Institute, San Sebastián, Spain CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain
| | - Luis Bujanda
- Departmenet of Gastroenterology, Donostia Hospital-Instituto Biodonostia, University of the Basque Country (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), San Sebastian, Spain
| | - María-José Sánchez
- CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Andalusian School of Public Health, Granada, Spain
| | - Esther Molina-Montes
- CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Andalusian School of Public Health, Granada, Spain
| | - Carmen Navarro
- CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Department of Epidemiology, Murcia Health Council, Murcia, Spain
| | - M Dolores Chirlaque
- CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Department of Epidemiology, Murcia Health Council, Murcia, Spain
| | - José MaríaHuerta
- CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Department of Epidemiology, Murcia Health Council, Murcia, Spain
| | - Eva Ardanaz
- CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Public Health Institute of Navarra, Pamplona, Spain
| | - Aurelio Barricarte
- CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Public Health Institute of Navarra, Pamplona, Spain
| | | | - Eric J Duell
- Unit of Nutrition, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain
| | - Elizabeth Hijona
- Departmenet of Gastroenterology, Donostia Hospital-Instituto Biodonostia, University of the Basque Country (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), San Sebastian, Spain
| | - Marta Herreros-Villanueva
- Departmenet of Gastroenterology, Donostia Hospital-Instituto Biodonostia, University of the Basque Country (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), San Sebastian, Spain
| | - Núria Sala
- Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain Unit of Nutrition, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain
| | - Miguel A Alfonso-Sánchez
- BIOMICs Research Group, 'Lucio Lascaray' Center for Research and Advanced Studies (CIEA), University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
| | - Marian M de Pancorbo
- BIOMICs Research Group, 'Lucio Lascaray' Center for Research and Advanced Studies (CIEA), University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
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Bell RL, Hauser S, Rodd ZA, Liang T, Sari Y, McClintick J, Rahman S, Engleman EA. A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2016; 126:179-261. [PMID: 27055615 PMCID: PMC4851471 DOI: 10.1016/bs.irn.2016.02.017] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general.
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Affiliation(s)
- R L Bell
- Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, United States.
| | - S Hauser
- Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Z A Rodd
- Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, United States
| | - T Liang
- Indiana University School of Medicine, Indianapolis, IN, United States
| | - Y Sari
- University of Toledo, Toledo, OH, United States
| | - J McClintick
- Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN, United States
| | - S Rahman
- Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD, United States
| | - E A Engleman
- Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, United States
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