Monthly Archives: April 2014

Interactive Effects of OPRM1 and DAT1 Genetic Variation on Subjective Responses to Alcohol

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  1. Lara A. Ray1,2,*,
  2. Spencer Bujarski1,
  3. Lindsay M. Squeglia3,
  4. James R. Ashenhurst1 and
  5. Raymond F. Anton4
  1. 1Department of Psychology, University of California, Los Angeles, CA, USA
  2. 2Department of Psychiatry, University of California, Los Angeles, CA, USA
  3. 3Department of Psychiatry, University of California, San Diego, CA, USA
  4. 4Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA
  1. *Corresponding author: Department of Psychology, University of California, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, USA. Tel.:+1-301-794-5383; Fax:+1-310-206-5895; E-mail: lararay{at}psych.ucla.edu.
  • Received May 21, 2013.
  • Revision requested July 9, 2013.
  • Revision received October 14, 2013.
  • Accepted October 15, 2013.

Abstract

Aims: Subjective response to alcohol represents a marker of alcoholism risk. The A118G single-nucleotide polymorphism (SNP) of the mu opioid receptor (OPRM1) gene has been associated with subjective response to alcohol. Recently, the dopamine transporter (DAT1) variable number of tandem repeat (VNTR; SLC6A3) has been found to interact with the OPRM1 A118G SNP in predicting neural and behavioral responses to naltrexone and to alcohol. This exploratory study examines the OPRM1 × DAT1 interaction on subjective responses to alcohol. Methods: Non-treatment-seeking problem drinkers (n = 295) were assessed in the laboratory for alcohol dependence. Following prospective genotyping for the OPRM1 gene, 43 alcohol-dependent individuals were randomized to two intravenous infusion sessions, one of alcohol (target BrAC = 0.06 g/dl) and one of saline. Measures of subjective responses to alcohol were administered in both infusion sessions. Results: Analyses revealed significant Alcohol × OPRM1 × DAT1 interactions for alcohol-induced stimulation, vigor and positive mood as well as significant Alcohol × OPRM1 × DAT1 × Time interactions for stimulation and positive mood. These effects were such that, compared with other genotype groups, OPRM1 G-allele carriers + DAT1 A10 homozygotes reported steeper increases in stimulation and positive mood across rising BrAC, when compared with placebo. All Alcohol × OPRM1 × DAT1 interactions remained significant when analyses were restricted to a subsample of Caucasian participants (n = 34); however, 4-way interactions did not reach statistical significance in this subsample. Conclusions: This study suggests that the contribution of OPRM1 genotype to alcohol-induced stimulation, vigor and positive mood is moderated by DAT1 genotype. These findings are consistent with the purported interaction between opioidergic and dopaminergic systems in determining the reinforcing properties of alcohol.

  1. Alcohol and Alcoholism

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

Pellagra and Alcoholism: A Biochemical Perspective

  1. Abdulla A.-B. Badawy*
  1. School of Health Sciences, Cardiff Metropolitan University, Western Avenue, Cardiff CF5 2YB, UK
  1. *Corresponding author: Tel.: +44-2920-416858; Fax: +44-2920-416982; E-mail: ABadawy{at}cardiffmet.ac.uk
  • Received January 20, 2014.
  • Revision requested February 10, 2014.
  • Revision received February 14, 2014.
  • Accepted February 17, 2014.

Historical and clinical aspects of pellagra and its relationship to alcoholism are reviewed from a biochemical perspective. Pellagra is caused by deficiency of niacin (nicotinic acid) and/or its tryptophan (Trp) precursor and is compounded by B vitamin deficiencies. Existence on maize or sorghum diets and loss of or failure to isolate niacin from them led to pellagra incidence in India, South Africa, Southern Europe in the 18th century and the USA following the civil war. Pellagra is also induced by drugs inhibiting the conversion of Trp to niacin and by conditions of gastrointestinal dysfunction. Skin photosensitivity in pellagra may be due to decreased synthesis of the Trp metabolite picolinic acid → zinc deficiency → decreased skin levels of the histidine metabolite urocanic acid and possibly also increased levels of the haem precursor 5-aminolaevulinic acid (5-ALA) and photo-reactive porphyrins. Depression in pellagra may be due to a serotonin deficiency caused by decreased Trp availability to the brain. Anxiety and other neurological disturbances may be caused by 5-ALA and the Trp metabolite kynurenic acid. Pellagra symptoms are resolved by niacin, but aggravated mainly by vitamin B6. Alcohol dependence can induce or aggravate pellagra by inducing malnutrition, gastrointestinal disturbances and B vitamin deficiencies, inhibiting the conversion of Trp to niacin and promoting the accumulation of 5-ALA and porphyrins. Alcoholic pellagra encephalopathy should be managed with niacin, other B vitamins and adequate protein nutrition. Future studies should explore the potential role of 5-ALA and also KA in the skin and neurological disturbances in pellagra.

Tryptophan Metabolism in Post-Withdrawal Alcohol-Dependent Patients

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  1. Gabriele v. Gleissenthall1,
  2. Simon Geisler2,
  3. Peter Malik1,
  4. Georg Kemmler1,
  5. Hannah Benicke1,
  6. Dietmar Fuchs2 and
  7. Sergei Mechtcheriakov1,*
  1. 1Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria
  2. 2Division of Biological Chemistry, Biocenter, Medical University Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria
  1. *Corresponding author: Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Tel: +43-512-504-23636; Fax: +43-512-504-23855; E-mail: s.mechtcheriakov{at}i-med.ac.at
  • Received December 2, 2013.
  • Revision requested January 29, 2014.
  • Revision received February 13, 2014.
  • Accepted February 18, 2014.

Abstract

Aims: The aim of the study was to investigate the parameters of tryptophan and phenylalanine metabolism and their associations to immune system activation and to behavioural symptoms during medium-term withdrawal (4–12 weeks of abstinence) in alcohol-dependent patients. Methods: Biochemical assays and clinical assessments at the beginning of treatment (fourth week of alcohol abstinence in average) and prior to the discharge after 8 weeks of treatment. Results: Kynurenine to tryptophan ratio (Kyn/Trp) slightly correlated with neopterin levels in early post-withdrawal period (Week 4 of abstinence) but this association disappeared after 12 weeks of abstinence. Phenylalanine and tyrosine concentrations as well as phenylalanine to tyrosine ratio (Phe/Tyr) decreased between Weeks 4 and 12 of abstinence. Kynurenine and Kyn/Trp increased significantly at 12th week of abstinence when compared with the beginning of the study (Week 4 of abstinence). At Week 12, Kyn/Trp significantly correlated with such behavioural symptoms as fatigue, irritability and sleep disturbances. Conclusions: Tryptophan breakdown in early stages may be influenced by the increased activity of indoleamine 2,3-dioxygenase but the increase of Kyn/Trp between Weeks 4 and 12 of abstinence seems to be independent of immune changes and correlates with behavioural symptoms in later stages of the post-withdrawal course. A possible role of kynurenine metabolites in mediation of the increased stress sensibility in post-withdrawal alcohol-dependent patients is discussed.

  1. Alcohol and Alcoholism

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

Severe Diffuse Axon Injury in Chronic Alcoholic Rat Medulla Oblongata Following a Concussion Blow

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Abstract

Aims: We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism. Methods: Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and β-APP proteins in the medulla oblongata were examined. Results: (a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of β-APP of the EtOH-TBI group was lower than that in the EtOH group (P < 0.05); the Tau IOD sum value of the EtOH-TBI group was higher than that in the EtOH group (P < 0.05). Conclusion: (a) Chronic alcoholism caused nerve fibre and neuronal morphology damage in the rat medulla oblongata, with structural damage becoming more significant following concussion. (b) Concussion changed the expression of β-APP and tau protein in chronic alcoholic rat medulla oblongata, suggesting that chronic alcoholism can lead to severe axonal injury following a concussion blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.

  1. Alcohol and Alcoholism

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

Association of Single-Nucleotide Polymorphisms in a Metabotropic Glutamate Receptor GRM3 Gene Subunit to Alcohol-Dependent Male Subjects

  1. Yan Xia1,,
  2. Zheng Wu1,,
  3. Dongying Ma2,
  4. Chunling Tang1,
  5. Lei Liu1,
  6. Feng Xin1,
  7. Daling Zhu3 and
  8. Jian Hu1,*
  1. 1Mental Health Institute, Harbin Medical University, Mental Health Centre, 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, Heilongjiang Province 150001, PR China
  2. 2Department of Neurosurgery, 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, Heilongjiang Province 150086, PR China
  3. 3Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing, Heilongjiang Province 163319, PR China
  1. * Corresponding author: Mental Health Institute, 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, Heilongjiang Province 150001, PR China. Tel.: +86 451 53674442; Fax: +86 13936170818. E-mail: hujian0451{at}163.com
  • Received March 9, 2013.
  • Revision requested April 19, 2013.
  • Revision received December 25, 2013.
  • Accepted January 9, 2014.

Aims: The purpose of this study was to investigate the association between the metabotropic glutamate receptor 3 (GRM3) subunit gene and alcohol dependence by the single-nucleotide polymorphisms (SNPs). Methods: Two hundred and forty-eight male alcohol-dependent patients and 235 male control subjects were recruited. Ten SNPs in the GRM3 region were studied, and genotyping of SNPs was performed by ligase detection reactions. Results: We found highly significant differences in allele and genotype frequencies of rs6465084 between the alcohol-dependent and control group, with the greater frequency of A allele of SNP rs6465084 in alcohol-dependent group. We also found significant differences of haplotype frequencies in five combinations (including TAATATT, CAGTATT, TCGTATT, CAATAGC, TAATATC) in the linkage disequilibrium constructed by seven SNPs between the groups. Conclusion: Our results supplied the first evidence that the polymorphism of GRM3 gene associates with the morbidity of alcohol dependence in human being, which may support a new potential target for alcoholism treatment.

OBITUARY: Professor Roger Nordmann

  1. Tomáš Zima
  1. President of ESBRA

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Professor Roger Nordmann, founder of the pioneering European Society for Biomedical Research on Alcoholism (ESBRA), passed away on Friday, 24 January 2014. His tireless dedication to the organization calls for a testimony to a remarkable profile of achievement, devotion and action.

Born on 24 May 1926 and raised in the city of Strasbourg, he attended high school at the Lycée Fustel de Coulanges, named after the historian Professor Numa Denis Fustel de Coulanges. Here, his extensive participation in the life of prestigious educational foundations began. Nordmann graduated Docteur en Médecine de l'Université de Paris in 1954, having already a diploma from the Institut Pasteur (named after Louis Pasteur and known for its leading biological, anatomical and medical research). He won particular recognition for his thesis, which marked just the beginning of his steps in the study of alcoholism and cancer.

At the young age of 28, after laboratory work as an assistant Biochemist, his talents led him to a rapid promotion as Head of Clinic at the Faculty of Medicine in Paris where he remained until 1955. …