The Alcohol Use Disorders Identification Test (AUDIT) has been developed from a six-country WHO collaborative project as a screening instrument for hazardous and harmful alcohol consumption. It is a 10-item questionnaire which covers the domains of alcohol consumption, drinking behaviour, and alcohol-related problems. Questions were selected from a 150-item assessment schedule (which was administered to 1888 persons attending representative primary health care facilities) on the basis of their representativeness for these conceptual domains and their perceived usefulness for intervention. Responses to each question are scored from 0 to 4, giving a maximum possible score of 40. Among those diagnosed as having hazardous or harmful alcohol use, 92% had an AUDIT score of 8 or more, and 94% of those with non-hazardous consumption had a score of less than 8. AUDIT provides a simple method of early detection of hazardous and harmful alcohol use in primary health care settings and is the first instrument of its type to be derived on the basis of a cross-national study.

/pdf/development-of-the-alcohol-use-disorders-identification-test-3h699nkijs.pdf

Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption-II

So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

Although the measurement of drinking is necessary for assessing and evaluating the treatment of alcohol problems, this key dependent variable has not always been reported in outcome studies.1, 2, 3 Today, the issue is not whether to measure drinking, but how to measure drinking. Concerns about how best to measure drinking patterns and problems date back to at least 1926, when Pearl stressed the importance of separating steady daily drinkers from occasional heavy drinkers.4

Timeline Follow-Back A Technique for Assessing Self-Reported Alcohol Consumption

The theory is advanced that the common denominator of a wide range of addictive substances is their ability to cause psychomotor activation. This view is related to the theory that all positive reinforcers activate a common biological mechanism associated with approach behaviors and that this mechanism has as one of its components dopaminergic fibers that project up the medial forebrain bundle from the midbrain to limbic and cortical regions. Evidence is reviewed that links both the reinforcing and locomotor-stimulating effects of both the psychomotor stimulants and the opiates to this brain mechanism. It is suggested that nicotine, caffeine, barbiturates, alcohol, benzodiazepines, cannabis, and phencyclidine----each ofwhich also has psychomotor stimulant actions--may activate the docaminergic fibers or their output circuitry. The role of physical dependence in addiction is suggested to vary from drug to drug and to be of secondary importance in the understanding of compulsive drug self-administration. Attempts at a general theory of addiction are attempts to isr late--from a variety of irrelevant actionsmthose drug actions that are responsible for habitual, compulsive, nonmedical drug self-administration. The common assumption of addiction theorists is that general principles of addiction can be learned from the study of one drug and that these principles will have heuristic value for the study of other drugs. Thus far, attempts at a general theory of addiction have failed to isolate common actions that can account for addiction across the range of major drug classes. A major stumbling block has been the psychomotor stimulants--amph etamine and cocainemwhich do not readily fit models traditionally based on depressant drug classes. The present article offers a new attempt at a general theory of addiction. It differs from earlier theories (e.g., Collier, 1968; Himmelsbach, 1943; Jaffe & Sharpless, 1968; Jellinek, 1960; Kalant, 1977; Lindsmith, 1947; Solomon & Corbit, 1974) in that it is based on the common denominator of the psychomotor stimulants---amphetamine, cocaine, and related drugs---rather than on the common denominator of the socalled depressant drugs~opiates, barbiturates, alcohol, and others. We take up two topics before presenting the new theory. First, we briefly discuss the heuristic value of a biological approach and suggest that the biologist's distinction between homology and analogy offers a useful insight. Next we discuss the shortcomings of earlier theories--variants of dependence theory. Then we outline the new theory and review the relevant evidence for its three major assertions: (a) that all addictive drugs have psychomotor stimulant actions, (b) that the stimulant actions of these different drugs have a shared biological mechanism, and (c) that the biological mechanism of these stimulant

A psychomotor stimulant theory of addiction

The drug abuse screening test.

1. Does Acetaldehyde Play a Role in Alcoholism? Behavioral versus Biochemical Analysis.- 2. Critical Explanations-Biological, Psychological, and Social-of Drinking Patterns and Problems from the Alcohol-Related Longitudinal Literature: Critiques and Strategies for Future Analyses on Behalf of the World Health Organization.- 3. Measuring Alcohol Consumption in the United States: Methods and Rationales.- 4. Alcohol and the Family: An International Review of the Literature with Implications for Research and Practice.- 5. The Origins of Modern Research and Responses Relevant to Problems of Alcohol: A Brief History of the First Center of Alcohol Studies.- 6. Drugs, Alcohol, and Aging.- 7. Stress and Coping Factors in the Epidemiology of Substance Use.- 8. Women, Illicit Drugs, and Crime.- 9. The Inverse Relationship between Tobacco Use and Body Weight.- 10. Effects of Abstinence from Tobacco: A Critical Review.

Research advances in alcohol and drug problems

RECEPTORS for dopamine have been classified into two functional types, D1 and D2 (refs 1,2). They belong to the family of receptors acting through G (or guanine nucleotide-binding) proteins3. D2 receptors inhibit adenylyl cyclase, but D1 receptors stimulate adenylyl cyclase and activate cyclic AMP-dependent protein kinases4,5. Dopamine D1 and D2 receptors are targets of drug therapy in many psychomotor disorders, including Parkinson's disease and schizophrenia6,7, and may also have a role in drug addiction and alchoholism8. D1 receptors regulate neuron growth and differentiation9, influence behaviour and modify dopamine D2 receptor-mediated events10,11. We report here the cloning of the D1 receptor gene, which resides on an intronless region on the long arm of chromosome 5, near two other members of the G-linked receptor family. The expressed protein, encoded by 446 amino acids, binds drugs with affinities identical to the native human D1 receptor. The presence of a D1 receptor gene restriction fragment length polymorphism will be helpful for future disease linkage studies.

Human dopamine D1 receptor encoded by an intronless gene on chromosome 5.

Immunization of mice with acetaldehyde conjugated to human plasma proteins resulted in the production of polyclonal antibodies that reacted with erythrocyte protein-acetaldehyde conjugates, but not with control erythrocyte proteins. Such antibodies recognized erythrocyte protein-acetaldehyde conjugates prepared with 20-100 microM acetaldehyde, concentrations that exist in the blood of alcoholics. The antibodies also recognized acetaldehyde condensation products with synthetic poly-(L-lysine). Immunization with keyhole limpet hemocyanin-acetaldehyde conjugates resulted in antibodies against both plasma protein-acetaldehyde and erythrocyte protein-acetaldehyde conjugates, which did not cross-react with the respective unmodified carrier proteins. Immunization with human erythrocyte protein-acetaldehyde condensates led to the production of antibodies against both the protein moiety as well as the condensate. Monoclonal antibodies with affinities 50 times greater for the condensate than for the carrier protein were produced by hybridization of spleen cells from the immunized mice. Chronic alcohol administration to mice for 45-50 days led to the generation of antibodies that reacted against protein-acetaldehyde conjugates, suggesting that such adducts are formed in vivo and can act as neoantigens. Antibodies against acetaldehyde adducts should be of value in the identification of alcohol consumption and in the study of the biology of the adducts in relation to organ pathology.

https://www.pnas.org/content/pnas/83/20/7923.full.pdf

Monoclonal and polyclonal antibodies against acetaldehyde-containing epitopes in acetaldehyde-protein adducts.

We have previously reported that a hypermetabolic state, resembling that produced by thryoid hormones, exists in the livers of animals treated chronically with ethanol. We propose that this alteration produces a relative hypoxia in the centrilobular zone of the liver which, if severe enough, leads to cellular death and to the production of hepatitis. Rats consuming ethanol for 30 days, given with a nutritionally adequate diet, and exposed to reduced oxygen tensions for only 6 hr, developed histological and biochemical evidence of hepatocellular necrosis and inflammatory lesions confined to the centrilobular zone. The severity was proportional to the degree of hypoxia. Pair-fed (nonalcohol) controls showed no such lesions. Treatment of the animals with propylthiouracil for 3-10 days abolished the hypermetabolic state of the liver in ethanol-consuming animals, and drastically reduced the histological and biochemical effects of hypoxia in them. These findings may have implications for pathogenesis and treatment of alcoholic hepatitis in man.

Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil.

In a study involving 68 ambulatory patients with known alcohol problems and 68 social drinkers matched for age and sex, a questionnaire about the patients' history of trauma identified 7 out of 10 subjects with drinking problems. In contrast, abnormal values for gamma-glutamyl transferase, mean corpuscular volume, or high-density lipoproteins had only moderate sensitivity (26% to 40%) for identifying alcohol problems but excellent specificity (88% to 99%) for ruling out cases. Similar rates of sensitivity and specificity were found among 61 family practice patients. Diagnostic accuracy was improved by combining tests results, using computer-based logistic regression analysis. This study suggests that a brief questionnaire on history of trauma is valuable for the earlier detection of problem drinking in ambulatory populations, in contrast to laboratory tests, which appear to have high sensitivity only with more chronic alcoholics.

Yedy Israel

Papers

Research advances in alcohol and drug problems

Human dopamine D1 receptor encoded by an intronless gene on chromosome 5.

Monoclonal and polyclonal antibodies against acetaldehyde-containing epitopes in acetaldehyde-protein adducts.

Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil.

Identification of Alcohol Abuse Using Laboratory Tests and a History of Trauma