Noble EP. The D-2 receptor gene: A review of association studies in alcoholism and phenotypes. Alcohol 16(1): 33–45, 1998. (119 refs.)
The role of the D-2 dopamine receptor (DRD2) gene in alcoholism and other substance use disorders has come under intense investigation since the minor TaqI A (Al) allele of the DRD2 gene was first reported to be associated with alcoholism. In a meta-analysis of 15 US and international studies of European (non-Hispanic) Caucasians, consisting of 1015 alcoholics (more severe and less severe) and 898 controls (unassessed and assessed for alcoholism), alcoholics had a higher prevalence (p < 10(-7), and frequency (p < 10(-5)) of the Al allele than controls. The prevalence of the Al allele was 1.5-fold higher in more severe than less severe alcoholics (p < 10(-4)), whereas unassessed controls had a twofold higher prevalence of the Al allele than assessed controls (p < 10(-4)). Whereas more severe alcoholics had a threefold higher Al allelic prevalence than assessed controls (p < 10(-10)), Al allelic prevalence was virtually identical in less severe alcoholics and in unassessed controls. The Al allele has also been associated with other drug problems including cocaine, nicotine, and polysubstance abuse. Furthermore, the minor TaqI B (B1) allele of the DRD2 gene has been associated with alcoholism and psychostimulant (cocaine, amphetamine) abuse. Beyond association studies, phenotypic differences exist between genotypes containing the TaqI A minor (A1A1 and A1A2) and major (A2A2) alleles of the DRD2. These different phenotypes have been identified through a number of approaches, including pharmacological, neurophysiological, neuropsychological, stress, personality, metabolic, and treatment studies. In conclusion, the present review suggests that the type of alcoholics and the nature of controls used are among critical factors in DRD2 association studies in alcoholism. Intronic mutations in both the 3'(TaqI A) and 5'(TaqI B) regions of the DRD2 associate with alcoholism and other drug use disorders. The identification of phenotypes of DRD2 genotypes suggests that the observed intronic DRD2 mutations may have functional consequences that predispose individuals to a variety of substance use disorders. Copyright 1998, Elsevier Science Inc.
Pittman DJ, White HR, eds. Society, Culture, and Drinking Patterns Reexamined. New Brunswick, NJ: Rutgers Center of Alcohol Studies, 1991.
Prescott CA, Aggen SH, Kendler KS. Sex differences in the sources of genetic liability to alcohol abuse and dependence in a population-based sample of US twins. Alcoholism: Clinical and Experimental Research 23(7): 1136–1144, 1999. (63 refs.)
Background: There are substantial sex differences In all levels of alcohol involvement among U.S, adults. The goal of this study was to test whether the magnitude and sources of genetic and environmental influences on liability for alcohol abuse and dependence differ for men and women. Methods: Structured personal interviews were used to assess DSM-III-R- and DSM-IV-defined alcohol abuse and dependence among 5091 male and 4168 female twins (including 1546 identical, 1128 same-sex fraternal, and 1423 opposite-sex pairs) born in Virginia between 1934 and 1974. Twin correlations were analyzed using structural equation modeling. Results: The magnitude of twin-pair resemblance was similar across several definitions of alcoholism and was substantially higher among identical than fraternal pairs. The proportion of population variation in liability attributed to genetic factors was substantial among both women (55-66%) and men (51-56%), and we found little evidence of a role of environmental factors shared by family members. In all definitions studied, we could reject a model that the genetic sources of liability in the two sexes overlap completely. Conclusion: In this first population-based study of alcoholism among male and female twins from the US., we found that genetic factors play a major role in the development of alcoholism in both sexes, that the magnitudes of genetic influence were equally high for men and women, and that the genetic sources of vulnerability are partially, but not completely, overlapping in men and women. Copyright 1999, Research Society on Alcoholism
Quickfall J., el-Guebaly N. Genetics and alcoholism: How close are we to potential clinical applications? (review). Canadian Journal of Psychiatry 51(7): 461–467, 2006. (79 refs.)
Rapid advancement of genetic knowledge has provided a wealth of data demonstrating a significant contribution of genes to the development of alcoholism but has suggested little in the way of clinical applicability. Twin and adoption studies suggest that 50% to 60% of the development of alcoholism is due to heritable factors, and linkage and association studies have identified chromosomal regions and individual genes that likely contribute to the development of this condition. Most of these genes are related to neurotransmitter systems and to alcohol metabolizing enzymes. We briefly review the evidence for this before discussing intermediate phenotypes of alcoholism under genetic control, pharmacogenetic aspects of alcoholism treatment, and the possibility of future clinical applications based on these areas. Copyright 2006, Canadian Psychiatric Association
Schuckit MA, Edenberg HJ, Kalmijn J, Flury L, Smith TL, Reich T, Bierut L, Goate A, Foroud T. A genome-wide search for genes that relate to a low level of response to alcohol. Alcoholism: Clinical and Experimental Research 25(3): 323–329, 2001. (32 refs.)
Background: The low level of response (LR) to alcohol is genetically influenced in both humans and animals, and a low LR is a characteristic of offspring of alcoholics that has been reported to predict alcoholism 10 and 15 years later. The genes that contribute to a low LR have not yet been identified. Methods: A 12-item questionnaire that measures LR, the Self Rating of the Effects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genetic material was available. These subjects were genotyped by using 336 markers with an average heterozygosity of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and qualitative nonparametric, sib-pair analyses were carried out for the SRE measure related to early drinking experiences. Results: Correlations of SRE scores across related individuals were significant and between 0.16 and 0.22 for most values, compared with nonsignificant correlations of 0.03 or less among unrelated individuals. Linkage analyses performed by using the FIRST 5 variables (first five times alcohol is consumed) identified four chromosomal regions with lod scores greater than or equal to2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample. Conclusions: These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon. Copyright 2001, Research Society on Alcoholism
Tatlow JR, Clapp JD, Hohman MM. The relationship between the geographic density of alcohol outlets and alcohol-related hospital admissions in San Diego County. Journal of Community Health 25(1): 79–88, 2000. (19 refs)
Increasing concerns regarding the cost of medical care have led to research that has found a relationship between alcohol abuse, increased medical problems, longer hospital stays, and higher medical costs. Research has also found a positive relationship between alcohol availability and crime, car accidents, and liver cirrhosis deaths. One area of interest is how alcohol availability, as measured by the number of alcohol outlets, is related to medical care needs. The purpose of this study was to examine the relationship between the geographic density of alcohol outlets and the number of alcohol-related hospital admissions. alcohol-related ICD-9 codes were selected based on epidemiologic research in the literature to determine alcohol-related morbidity from the California Discharge Data System, which collects information on all hospital admissions and discharges in California. In San Diego County, in 1996, 3,759 admissions were alcohol-related. Alcohol-related admissions for each zip code were compared to the number of liquor licenses that were held by each zip code through a multiple regression analysis. The regression model demonstrated that the number of liquor outlets was a significant predictor of alcohol-related hospital admissions, net of other predictors. Implications are discussed, including regulation of alcohol availability, which may have a beneficial impact on alcohol morbidity. Copyright 2000, Human Sciences Press, Inc.
Tyndale RF. Genetics of alcohol and tobacco use in humans (review). Annals of Medicine 35(2): 94–121, 2003. (352 refs.)
The field of genetics holds great promise for furthering our understanding of the etiology of drug dependence and for identifying novel targets for treatment. Genetic studies utilizing twins and families have demonstrated a considerable role for genetics in nicotine and/or alcohol dependence. Risk for alcoholism or nicotine dependence is likely to be the result of a large number of genes, each contributing a small fraction of the overall risk. While this review will focus on studies in humans, many of the candidate genes for human nicotine and alcohol dependence listed here were originally postulated to be important, based on data from animal studies. The review will briefly summarize the results from twin and adoption studies that provide estimations of heritability, the results from chromosomal linkage studies that identify regions of chromosomes that may contain relevant genes, and the results of candidate gene studies. For each topic the data will be presented for nicotine dependence, alcohol dependence, and for nicotine and alcohol dependence together. In addition, each section will review briefly some of the confounding issues in the specific type of approach utilized. (Copyright 2003, Finnish Medical Society)
Vaillant GE. The Natural History of Alcoholism, Revisited. Cambridge, MA: Harvard University Press, 1995.
This volume represents both a "re-printing", as well an up-dating and reflection on a now classic work in the alcohol field, one published fifteen year ago. Drawing upon the analysis of two major longitudinal studies, that work described the natural history of alcoholism (alcohol dependence.) The "new" edition is structured as a "reprint" of the previous edition, with new sections interspersed -- clearly denoted -- providing a commentary on the earlier work, drawing upon new research in the field, further follow-up of subjects, and the author's reflections.
Wagenaar AC, Harwood EM, Toomey TL, Denk CE, Zander KM. Public opinion on alcohol policies in the United States: Results from a national survey. Journal of Public Policy 21(3): 303–327, 2000. (47 refs.)
We surveyed the U.S. non-institutionalized population age 18+ on opinions regarding 23 alcohol control policies (N = 7,021). The cooperation rate among contacted households was 70% and the overall response rate was 54%. Results showed high levels of public support for most alcohol control policies. Over 80% support restrictions on alcohol use in public places, such as parks, beaches, concert venues, and on college campuses. Eighty-two percent support increased alcohol taxes, provided the funds are used for treatment or prevention programs. Over 60% support alcohol advertising and promotion restrictions, such as banning billboard advertising, banning promotion at sporting events, or banning liquor and beer advertising on television. Copyright 2000, Journal of Public Policy, Inc.
Zhou Q, King KM, Chassin L. The roles of familial alcoholism and adolescent family harmony in young adults’ substance dependence disorders: Mediated and moderated relations. Journal of Abnormal Psychology 115(2): 320–331, 2006. (70 refs.)
This study examined the prospective relations among family history density of alcoholism (FHD), adolescent family harmony, and young adults' alcohol and drug dependence. Family harmony was rated by mothers and fathers in adolescence, and young adults' substance dependence diagnoses were obtained through structured interviews. Higher FHD predicted lower adolescent family harmony, which in turn increased young adults' odds of being diagnosed with drug dependence (with and without alcohol dependence) compared to no diagnoses or to alcohol dependence only. Family harmony also interacted with FHD such that the protective effect of family harmony on young adults' drug dependence with or without alcohol dependence decreased as FHD rose, and was nonsignificant at high levels of FHD. The findings suggest the importance of distinguishing among alcohol and drug dependence disorders and examining their differential etiological pathways, and also suggest that the protective effects of harmonious family environments on substance dependence may be limited at high levels of FHD. (Copyright 2006, American Psychological Association)
Chapter 6 Medical Complications
Alcohol Health and Research World 21(1): entire issue, 1997.
This thematic issue deals with effects of alcohol on the gastrointestinal system.
Available online < http://pubs.niaaa.nih.gov/Publications/AlcoholResearch/>
Alcohol Health and Research World 21(2): entire issue, 1997.
This thematic issue deals with neurobiology and the impact of alcohol on the brain.
Available online < http://pubs.niaaa.nih.gov/Publications/AlcoholResearch/>
Al-Jarallah KF, Shehab DK, Buchanan WW: Rheumatic complications of alcohol abuse (review), Seminars in Arthritis and Rheumatism 22(3): 162–171, 1992.
The purpose of this report is to review rheumatic complications associated with alcoholism. Data were collected by an English-language literature search using MEDLINE (1966 to December 1991) and references from identified articles. Studies in humans, including case reports of joint disease and allied disorders associated with alcoholism, were reviewed. According to the data identified, alcoholism is associated with many rheumatic problems, including neuropathic arthropathy, hyperuricemia with gouty arthritis, septic arthritis, and joint hypermobility. Osteoporosis, osteonecrosis, and myopathy also are common. Several other rare musculoskeletal complications have been described. Early recognition of these problems is important for management. Further studies are needed to examine the effect of alcohol on connective tissue components in joints. Copyright 1992, W.B. Saunders Co.
Apte MV; Wilson JS. Alcohol-induced pancreatic injury. (review) Best Practice & Research. Clinical Gastroenterology 17(4): 593-612, 2003. (140 refs)
Alcoholic pancreatitis is a major complication of alcohol abuse. Until recently, it was generally accepted that alcoholic pancreatitis was a chronic disease from the outset. However, evidence is now emerging in support of the 'necrosis-fibrosis' hypothesis that alcoholic pancreatitis begins as an acute process and that repeated episodes of acute injury lead to the changes of chronic pancreatitis (acinar atrophy and fibrosis) resulting in exocrine and endocrine dysfunction. The treatment of acute pancreatitis follows the regimen of bed rest, nasogastric suction, analgesia and intravenous support. The role of additional therapeutic measures such as prophylactic antibiotics, antioxidants and enteral nutrition in severe cases has not yet been precisely defined. The treatment of chronic pancreatitis involves attention to its three cardinal features: pain, maldigestion and diabetes. With respect to the pathogenesis of alcoholic pancreatitis, the focus of research over the past 30 years has shifted from the sphincter of Oddi and ductular abnormalities to the acinar cell itself. It has now been established that the acinar cell is capable of metabolizing alcohol and that direct toxic effects of alcohol and/or its metabolites on acinar cells may predispose the gland to injury in the presence of an appropriate trigger factor. A significant recent development relates to the characterization of pancreatic stellate cells, increasingly implicated in alcoholic pancreatic fibrosis. This chapter summarizes the natural history, clinical features, current trends in treatment as well as recent advances in our understanding of the pathogenesis of alcoholic pancreatitis. Copyright 2003, Elsevier Science
Ashley MJ; Rehm J; Bondy S; Single E; Rankin J. Beyond ischemic heart disease: Are there other health benefits from drinking alcohol? Contemporary Drug Problems 27(4): 735-777, 2000. (208 refs.)
Evidence is growing that alcohol consumption confers health benefits beyond protection from ischemic heart disease. We review this evidence with regard to cerebrovascular disease, peripheral vascular disease, diabetes, cholelithiasis (gallstones), cognitive functioning, and stress reduction and subjective psychosocial benefits. Other possible benefits are briefly considered. The weight of evidence suggests that low-level alcohol consumption offers some protection against ischemic stroke. The evidence that moderate alcohol consumption protects against diabetes and gallstones is also fairly strong. The possibility of other health benefits cannot be dismissed. For all the conditions considered, more research is indicated. The application of more appropriate statistical techniques, studies of patterns of drinking, and experimental approaches to delineating underlying mechanisms should enable firmer conclusions to be drawn. A better understanding of both the benefits and the risks of alcohol use for individuals and populations will facilitate the development of appropriate program and policy interventions to promote health. Copyright 2000, Federal Legal Publications, Inc.
Bates ME; Bowden SC; Barry D. Neurocognitive impairment associated with alcohol use disorders: Implications for treatment. (review) Experimental and Clinical Psychopharmacology 10(3): 193-212, 2002. (200 refs.)
Between 50% and 80% of individuals with alcohol use disorders experience mild to severe neurocognitive impairment. There is a strong clinical rationale that neurocognitive impairment is an important source of individual difference affecting many aspects of addiction treatment, but empirical tests of the direct influence of impairment on treatment outcome have yielded weak and inconsistent results. The authors address the schism between applied-theoretical perspectives and research evidence by suggesting alternative conceptual models of the relationship between neurocognitive impairment and addiction treatment outcome. Methods to promote neurocognitive recovery and ways in which addiction treatments may be modified to improve psychosocial adaptation are suggested. Specific suggestions for future research that may help clarify the complex relations between neurocognitive impairment and addiction treatment are outlined. Copyright 2002, American Psychological Association
Beatty WW, Tivis R, Stott HD, Nixon SJ, Parsons OA. Neuropsychological deficits in sober alcoholics: Influences of chronicity and recent alcohol consumption. Alcoholism: Clinical and Experimental Research 24(2): 149-154, 2000. (29 refs.)
Background: The relationships between severity of neuropsychological (NP) deficits and quantity and duration of alcoholic drinking remain controversial. Eckardt et al. (1998) proposed that NP deficits can be observed only if chronicity of alcohol abuse equals or exceeds 10 years. In this study we tested the hypothesis of Eckardt et al. and reexamined the relationship of NP performance and alcohol consumption. Methods: One hundred sixty-two alcoholics and 165 controls completed a NP test battery at least 3 weeks after the alcoholics attained sobriety. Chronicity varied from 4 to 9 years for 55 alcoholics and from 10 to 33 years for the remaining 107. Results: Compared to controls, both groups of alcoholics were impaired on the Shipley Vocabulary and Abstraction tests and on two versions of the Digit Symbol test, but there was no difference between the two alcoholic groups on any measure. Regression analyses that controlled for age and education showed that chronicity predicted less than 0.5% of the variance on NP measures. By contrast, a measure of recent alcohol consumption, the Quantity-Frequency Index, contributed significantly (approximately 5% of the variance) to the prediction of alcoholics' NP performance. Conclusions: These data provide weak support for a dose effect relationship between degree of NP impairment and level of alcoholic drinking in the past 6 months but no evidence for an influence of chronicity. Copyright 2000, Research Society on Alcoholism
Bondy SJ; Rehm J; Ashley MJ; Walsh G; Single E; Room R. Low-risk drinking guidelines: The scientific evidence. (review). Canadian Journal of Public Health 90(4): 264-270, 1999. (83 refs.)
In 1997 the Addiction Research Foundation of Ontario and Canadian Centre on Substance Abuse released updated guidelines for low-risk alcohol consumption. This paper presents the scientific rationale behind this statement. Important comprehensive overviews on the consequences of alcohol use were studied. Formal meta-analyses on morbidity and mortality were examined wherever possible. Individual elements from similar guidelines were investigated for their scientific foundation. Limited original analyses defined risk levels by average weekly consumption. The evidence reviewed demonstrated that placing limits on both daily intake and cumulative intake over the typical week is justifiable for the prevention of important causes of morbidity and mortality. Gender-specific limits on weekly consumption were also indicated. In these updated guidelines intended for primary prevention, days of abstinence are not necessarily recommended. Intoxication should be avoided and abstinence is sometimes advisable. Available evidence does not strongly favour one alcoholic beverage over another for cardiovascular health benefits. Copyright 1999, Canadian Public Health Association
Bujanda L. The effects of alcohol consumption upon the gastrointestinal tract. (review). American Journal of Gastroenterology 95(12): 3374-3382, 2000. (84 refs.)
Regardless of the type and dose of beverage involved, alcohol facilitates the development of gastroesophageal reflux disease by reducing the pressure of the lower esophageal sphincter and esophageal motility. Fermented and nondistilled alcoholic beverages increase gastrin levels and acid secretion. Succinic and maleic acid contained in certain alcoholic drinks also stimulate acid secretion. Low alcohol doses accelerate gastric emptying, whereas high doses delay emptying and slow bowel motility. Alcohol facilitates the development of superficial gastritis and chronic atrophic gastritis- though it has not been shown to cause peptic ulcer. Alcoholic beverages, fundamentally wine, have important bactericidal effects upon Helicobacter pylori and enteropathogenic bacteria. The main alcohol-related intestinal alterations are diarrhea and malabsorption, with recovery after restoring a normal diet. Alcohol facilitates the development of oropharyngeal, esophageal, gastric, and colon cancer. Initial research suggests that wine may be comparatively less carcinogenic. Copyright 2000, American College of Gastroenterology
Chen W-JA; /Maier SE; /Parnell SE; West JR. Alcohol and the developing brain: Neuroanatomical studies. Alcohol Research & Health 27(2): 174-180, 2003. (48 refs)
One of the distinguishing features of prenatal alcohol exposure is impaired cognitive and behavioral function resulting from damage to the central nervous system. Information available from the small number of autopsied cases in humans indicates that the offspring of mothers who abused alcohol during pregnancy have various neuroanatomical alterations ranging from gross reductions in brain size to cellular alterations. Recent neuroimaging technology provides the most powerful tool for assessing the neurotoxic effects of fetal alcohol exposure in living organisms and for exploring the relationship between behavioral dysfunction and brain damage at the regional level. Recently, animal research has suggested that the damaging effects of alcohol exposure during brain development could be prevented or attenuated by various pharmacological manipulations or by complex motor training. These promising findings provide directions for developing future prevention or intervention strategies. Public Domain
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