5/31/98Bibliography (partial) with abstracts for AlcoholAmerican Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. Conigrave, K. M., J. B. Saunders, et al. (1995). "Diagnostic tests for alcohol consumption." Alcohol Alcohol 30(1): 13-26. A variety of laboratory tests are available to assist in the diagnosis of hazardous alcohol consumption and related disorders. Standard tests, such as serum gamma glutamyltransferase activity and erythrocyte mean cell volume, have limited sensitivity, particularly in detecting non- dependent hazardous consumption. Most also have poor specificity in that results are affected by common diseases and medications. Over the past 10 years a number of new laboratory tests have emerged. One of these, carbohydrate deficient transferrin, has high sensitivity in detecting persons with alcohol dependence, and shows promise for identification of non-dependent hazardous drinking; it is also highly specific. Others such as measurement of bound acetaldehyde, serum beta- hexosaminidase and the ratio of urinary serotonin metabolites offer promise in detecting recent heavy drinking. However, many issues remain unresolved. The newer markers have often been judged by contrasting their values in patients who are clearly alcohol dependent and abstainers or very light drinkers. It is now apparent that some are relatively insensitive markers of hazardous consumption. Future research needs to examine the performance of these markers among subjects with a range of alcohol intakes to fully determine their value in assessing drinking history. In addition, assays which are capable of some degree of automation need to be developed for analysing large numbers of samples. Ewing, J. A. (1984). "Detecting alcoholism. The CAGE questionnaire." Jama252(14): 1905-7. Four clinical interview questions, the CAGE questions, have proved useful in helping to make a diagnosis of alcoholism. The questions focus on Cutting down, Annoyance by criticism, Guilty feeling, and Eye- openers. The acronym "CAGE" helps the physician to recall the questions. How these questions were identified and their use in clinical and research studies are described. Frezza, M., C. di Padova, et al. (1990). "High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism [published errata appear in N Engl J Med 1990 May 24;322(21):1540 and 1990 Aug 23;323(8):553] [see comments]." N Engl J Med 322(2): 95-9. After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease. Recently, we documented significant "first-pass metabolism" of ethanol due to its oxidation by gastric tissue. We report a study of the possible contribution of this metabolism to the sex-related difference in blood alcohol concentrations in 20 men and 23 women. Six in each group were alcoholics. The first-pass metabolism was determined on the basis of the difference in areas under the curves of blood alcohol concentrations after intravenous and oral administration of ethanol (0.3 g per kilogram of body weight). Alcohol dehydrogenase activity was also measured in endoscopic gastric biopsies. In nonalcoholic subjects, the first-pass metabolism and gastric alcohol dehydrogenase activity of the women were 23 and 59 percent, respectively, of those in the men, and there was a significant correlation (rs = 0.659) between first-pass metabolism and gastric mucosal alcohol dehydrogenase activity. In the alcoholic men, the first-pass metabolism and gastric alcohol dehydrogenase activity were about half those in the nonalcoholic men; in the alcoholic women, the gastric mucosal alcohol dehydrogenase activity was even lower than in the alcoholic men, and first-pass metabolism was virtually abolished. We conclude that the increased bioavailability of ethanol resulting from decreased gastric oxidation of ethanol may contribute to the enhanced vulnerability of women to acute and chronic complications of alcoholism. Hoffman, P. L. and B. Tabakoff (1996). "Alcohol dependence: a commentary on mechanisms." Alcohol Alcohol 31(4): 333-40. The alcohol dependence syndrome includes the presence of alcohol tolerance, physical dependence and an inability to control one's alcohol intake. Studies are reviewed that implicate the mesolimbic dopaminergic systems, and the gamma-aminobutyric acid-A (GABAA) and N- methyl-D-aspartate (NMDA) receptors as mediators of various aspects of the alcohol dependence syndrome. It is suggested that alcohol-induced changes in the GABAA receptor may play a role in certain aspects of tolerance to alcohol and in altered abilities of an individual to terminate alcohol intake. Chronic alcohol-induced increases in the activity of NMDA receptors may contribute to the withdrawal signs that are the defining feature of physical dependence on alcohol. It is hypothesized that decreased mesolimbic dopaminergic function, which occurs during alcohol withdrawal, may be involved in the compulsion to initiate and maintain alcohol drinking, another aspect of the alcohol dependence syndrome. Furthermore, evidence is presented that this decreased dopaminergic function could occur secondarily to the increase in NMDA receptor function, such that the alcohol-induced increase in NMDA receptor function could underlie both the overt withdrawal signs and the compulsion to drink alcohol in the alcohol-dependent individual. Jellinek, E. (1960). The Disease Concept of Alcoholism. New Haven, Hillhouse Press. Jessor, R., H. B. Young, et al. (1970). "Perceived opportunity, alienation, and drinking behavior among Italian and American youth." J Pers Soc Psychol 15(3): 215-22. Naranjo, C. A. and K. E. Bremner (1993). "Behavioural correlates of alcohol intoxication." Addiction 88(1): 25-35. Alcohol is used in most cultures despite knowledge of the physical, psychological and social problems associated with its abuse. Behavioural impairment is a function of several factors, including blood alcohol concentration (BAC) and the rate of alcohol metabolism by alcohol dehydrogenase and the microsomal ethanol-oxidizing system. Their availability and activity depend upon alcohol use history, ethnicity, other drug use and gender. Adverse social consequences related to alcohol intoxication include impaired driving, acts of aggression and violence towards self and others, and various types of accidents. About 40% of all fatal traffic accidents in Canada and the US in 1986-1987 were alcohol-related. Similar statistics have been reported in the UK and Europe (e.g. Sweden). The risk of a fatal car accident increases exponentially with a driver's BAC, prompting recommendations to lower the legal BAC limit for driving and piloting aircraft. Risks of falls, drownings, and fires and burns may also be increased by alcohol intoxication. At least 22% of work-related accidents may have involved alcohol use. These data are probably conservative estimates as under-reporting of alcohol use is likely. Alcohol facilitates aggressive behaviours, but it is difficult to separate the pharmacological effect from psychosocial effects or some other common factor (e.g. low CSF levels of the serotonin metabolite 5- H1AA have been reported in alcoholics, suicide attempters, violent offenders). In addition, alcohol interacts with other drugs to increase or decrease their behavioural and therapeutic effects. An acutely high BAC inhibits the metabolism of other CNS depressants (e.g. benzodiazepines), but long-term alcohol use increases the metabolism of most drugs. A potential amethystic agent, to block or reverse alcohol's effects, has been identified in preclinical studies (Ro15-4513, an imidazobenzodiazepine). Some clinical studies indicated that naloxone, lithium, ibuprofen, zimeldine and catecholamine agonists may reduce ethanol-induced behavioural or cognitive effects but the results have not been consistently replicated. More research is needed to determine the potential clinical use of amethystic agents and other pharmacotherapies in the prevention and treatment of problem behaviours associated with alcohol abuse and intoxication. Schmidt, L. G., K. Schmidt, et al. (1997). "Superiority of carbohydrate-deficient transferrin to gamma- glutamyltransferase in detecting relapse in alcoholism." Am J Psychiatry 154(1): 75-80. OBJECTIVE: The usefulness of carbohydrate-deficient transferrin is widely accepted in screening (male) population samples for heavy alcohol consumption, but its role in relapse detection is not convincingly established. The authors therefore compared the diagnostic value of carbohydrate-deficient transferrin with the commonly used gamma-glutamyltransferase in identifying relapsed alcoholics during outpatient aftercare. METHOD: The patients were 101 male alcoholics who entered a 6-month rehabilitation program after hospital detoxification. Drinking status was assessed by means of self- and collateral reports obtained during regular contacts with the rehabilitation team; relapse was defined as consumption of any alcohol. Visits occurred weekly during month 1, biweekly during month 2, and every 4 weeks during months 3-6. At every visit a blood sample was taken for measurement of carbohydrate-deficient transferrin and gamma-glutamyltransferase. RESULTS: The proportion of men who reported relapse was 25.6% per scheduled contact on average. Positive predictive values indicated that relapse was identified with a 76.2% probability by carbohydrate- deficient transferrin values above the upper normal limit, in contrast to a 32.9% chance with gamma-glutamyltransferase. Carbohydrate- deficient transferrin was especially useful in detecting early relapses during the initial rehabilitation phase, when gamma-glutamyltransferase values had not normalized. Because of the longer half-life of gamma- glutamyltransferase, it had some value with a 4-week monitoring schedule in detecting new drinking episodes in alcoholics whose previous results had been normal. CONCLUSIONS: Carbohydrate-deficient transferrin proved to be superior to gamma-glutamyltransferase in relapse detection in an outpatient care setting for alcoholics. Tarter, R. E., A. I. Alterman, et al. (1985). "Vulnerability to alcoholism in men: a behavior-genetic perspective." J Stud Alcohol 46(4): 329-56. The psychological and biological characteristics associated with the vulnerability to alcoholism are reviewed. The predisposing features can be accounted for on the basis of deviations in empirically established temperament traits, thereby supporting the viability of a behavior- genetic perspective for elucidating the susceptibility to alcoholism. The temperament perspective also has heuristic value for improving our understanding of the neurobiological mechanisms that link the genetic predisposition to overt behavior. In addition, the temperament approach has ramifications for the prevention and treatment of alcoholism, as well as for clarifying the etiology and classification of certain other psychiatric disorders. The questions of what may be inherited in alcoholism and how this information can be usefully applied to enhance our knowledge of alcoholism etiology, prevention and clinical management are addressed. Tsai, G., D. R. Gastfriend, et al. (1995). "The glutamatergic basis of human alcoholism [see comments]." Am J Psychiatry 152(3): 332-40. OBJECTIVE: Although alcoholism is one of the most common psychiatric diagnoses, understanding of its pathophysiology remains poor. Accumulating evidence suggests that neurophysiological and pathological effects of ethanol are mediated to a considerable extent through the glutamatergic system. This article reviews the evidence of ethanol's effects on glutamatergic transmission and proposes a glutamatergic basis for alcoholism. METHOD: The information was derived from original research. The authors located more than 100 articles from psychiatry and neuroscience journals that related ethanol to glutamatergic transmission. They critically reviewed the neurobiology of the glutamatergic system in alcoholism and synthesized a unifying glutamatergic theory. RESULTS: Acute effects of ethanol disrupt glutamatergic neurotransmission by inhibiting the response of the N- methyl-D-aspartate (NMDA) receptor. Prolonged inhibition of the NMDA receptor by ethanol results in development of supersensitivity; acute removal of ethanol causes marked augmentation of activity of postsynaptic neurons, such as those in the noradrenergic system, and, in the extreme, glutamate-induced excitotoxicity. Neurobiological effects of alcoholism, such as intoxication, withdrawal seizures, delirium tremens, Wernicke-Korsakoff syndrome, and fetal alcohol syndrome, can be understood as a spectrum of consequences of ethanol's effect on the glutamatergic system. CONCLUSIONS: A host of findings support the hypothesis that the unifying mechanism of action of ethanol in interference with glutamatergic neurotransmission, especially through the NMDA receptor. Alcoholism may be considered another member of the expanding family of glutamate-related neuropsychiatric disorders. These insights should increase understanding of the biologic vulnerabilities leading to ethanol abuse and dependence and aid development of more effective pharmacologic interventions.
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