Guilherme Borges, Liliana Mondragón, Maria Elena Medina-mora, Ricardo Orozco, Joaquin Zambrano, and Cheryl Cherpitel.  A case-control study of alcohol and substance use disorders as risk factors for non-fatal injury.  Alcohol and Alcoholism 40(4):257-262, July/August 2005.

Summary: Using a case-control study design the authors examined the association of alcohol use disorders (AUD) and substance use disorders (SUD) and the risk of non-fatal injuries. AUD and SUD were diagnosed according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the International Classification of Diseases, Version 10 (ICD-10). The cases were injured patients (n = 653) 18–65-years-old who attended one emergency department (ED). The controls were subjects (n = 1,131) of the same age group from a representative sample of Mexico City residents. Information on drug and alcohol use was obtained by interview using the World Mental Health version of the Composite International Diagnostic Interview (WMH-CIDI). Among injured patients, the prevalence of substance abuse or dependence within the last 12 months was 12.3% for alcohol and 2.5% for other substances (marijuana, cocaine, tranquilizers, amphetamines, others), compared to 1.8% and 0.3% respectively among controls. Adjusted odds ratios (OR) of injury were 4.95 (95% confidence interval [CI], 2.87–8.52) for alcohol use and 2.58 (95% CI, 0.73–9.17) for other substance use. A significant level of comorbid alcohol and substance use disorders was also found. The authors conclude that efforts should be made to treat or refer ED patients with alcohol and substance use disorders, and that special care should be taken to address comorbid cases. NIAAA Glossary Terms:  AOD abuse, AOD dependence, alcohol use disorder classification, accident, injury, trauma, diagnostic criteria, emergency care, case-control study, Mexico, interview, prevalence, marijuana in any form, cocaine, tranquilizers, amphetamines, risk analysis, risk factors, relative risk, comorbidity, multiple drug use, human study

Kerrianne Watt, David M. Purdie, Ann M. Roche, and Roderick J. Mcclure.  The relationship between acute alcohol consumption and consequent injury type.  Alcohol and Alcoholism 40(4):263-268, July/August 2005.

Summary: The relationship between acute alcohol consumption and injury type (nature of injury, body region injured) was quantified in a cross-sectional study, with adjustment for the effect of known confounders (demographic and situational variables, usual drinking patterns, substance use, and risk-taking behavior). The study was conducted between October, 2000 and October, 2001. The participants were patients aged ≥15 years presenting to an emergency department for treatment of an injury sustained in the preceding 24 hours. Three measures of acute alcohol consumption were used: drinking setting, quantity, and beverage type consumed in the 6 hours before injury. Two variables were used to quantify injury type: nature of injury (fracture/dislocation, superficial, internal, and central nervous system injury) and body part injured (head/neck, face, chest, abdomen, external, and extremities). Both were derived from patient medical records. Interviews were conducted with 593 patients. After controlling for relevant confounding variables, logistic regression analyses indicated that there was no significant association between any of the three measures of acute alcohol consumption and injury type. The authors concluded that the effects of acute alcohol consumption are not specific to injury type, and that interventions aimed at reducing the incidence of alcohol-related injury should not be targeted at specific injury types. NIAAA Glossary Terms:  AOD use pattern, binge AOD use, AOD intake per occasion, acute AODE, accident, injury, trauma, emergency care, alcoholic beverage, drinking venue, bone fracture, skeletal system, central nervous system, head injury, neck, face, thorax, abdomen, arm, leg, medical history, interview, cross-sectional study, confounding variable, human study

Olli Savola, Onni Niemelä, and Matti Hillbom.  Alcohol intake and the pattern of trauma in young adults and working aged people admitted after trauma.  Alcohol and Alcoholism 40(4):269-273, July/August 2005.

Summary: The relationship of different patterns of alcohol intake to various types of trauma was investigated in a series of consecutive trauma admissions (N = 385; 278 men, 107 women; 16–49 years old). Patients underwent clinical examinations, structured interviews on the amount and pattern of alcohol intake, and measurements of blood alcohol concentration (BAC).  Blood alcohol was detected in 51% of the patients on admission. Binge drinking was the predominant (78%) drinking pattern. Assaults, falls, and biking accidents were the most frequent causes of trauma. Dependent alcohol drinking and binge drinking were significantly more common among patients with head trauma than in those with other types of trauma (77% vs 59%, odds ratio [OR] = 2.38; 95% confidence interval [CI], 1.50–3.77). The OR for sustaining head injury increased sharply with increasing BAC: 1–99 mg/dl, OR = 1.24 (95% CI, 0.55–2.01); 100–149 mg/dl, OR = 1.64 (95% CI, 0.71–3.77), 150–199 mg/dl, OR = 3.20 (95% CI, 1.57–6.53); and >199 mg/dl, OR = 9.23 (95% CI, 4.79–17.79). In conclusion: (1) Binge drinking is a major risk factor for head trauma among trauma patients. (2) Assaults, falls, and biking accidents are the commonest causes for such injuries. (3) The relative risk for head injury markedly increases with increasing BAC. The authors believe that alcohol control measures should feature in policies aiming at preventing trauma-related morbidity and mortality. NIAAA Glossary Terms:  AOD use pattern, AOD consumption, accident, injury, trauma, emergency care, interview, BAC level, binge AOD use, AOD dependence, risk analysis, risk factors, relative risk, head injury, assault and battery, accidental fall, dose-response relationship, human study

Magorzata Bednarska-Makaruk, Maria Rodo, Cezary Markuszewski, Anna Rozenfeld, Magorzata Swiderska, Boguslaw Habrat, and Hanna Wehr.  Polymorphisms of apolipoprotein E and angiotensin-converting enzyme genes and carotid atherosclerosis in heavy drinkers.  Alcohol and Alcoholism 40(4):274-282, July/August 2005.

Summary: The authors investigated the influence of gene polymorphisms of apolipoprotein E (APO E) and angiotensin-converting enzyme (ACE) on carotid artery atherosclerosis in alcohol dependence. Polymorphism of both genes was identified by deoxyribonucleic acid (DNA) analysis in male alcohol-dependent patients (N = 130). Intima-media thickness (IMT) was measured by ultrasonography. Multivariate regression analysis revealed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, low-density lipoprotein (LDL) cholesterol, and fasting plasma glucose levels. Subjects carrying the APO E ε4 allele were more likely to develop atherosclerotic changes in carotid arteries compared with subjects with the ε3/3 genotype (statistically significant in patients under age 50 years). No association was shown between ACE I/D polymorphism and carotid atherosclerosis. Thus APO E polymorphism can increase the risk of carotid atherosclerosis development in alcoholics. The association of the APO E ε4 allele with carotid atherosclerosis was significant in younger patients. Since elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis, the consequences could involve both cardiac and cerebrovascular events. NIAAA Glossary Terms:  genetic polymorphism, allele, genotype, AOD dependence, apolipoproteins, angiotensin, athersclerosis, carotid artery, DNA, ultrasonography, multivariate analysis, regression analysis, risk factors, age differences, hypertensive disorder, low density lipoprotein, cholesterol, glucose, plasma, genetic markers, myocardial ischemia, stroke, human study

M. Ceccanti, R. Mancinelli, G. F. Sasso, J. P. Allen, R. Binetti, A. Mellini, F. Attilia, L. Toppo, and M. L. Attilia.  Erythrocyte thiamine (Th) esters: a major factor of the alcohol withdrawal syndrome or a candidate marker for alcoholism itself?  Alcohol and Alcoholism 40(4):283-290, July/August 2005.

Summary: This study investigated the relationship of alcohol withdrawal syndrome to thiamine and thiamine esters, as well as the diagnostic power of thiamine and its esters. Thiamine and its esters were assessed in a series of alcoholics and in controls using an improved method. No association was found between alcohol withdrawal syndrome severity and thiamine and its esters, although the diagnostic power of thiamine diphosphate and thiamine was very high. Thiamine diphosphate was the most significant among the parameters studied, confirming that erythrocyte thiamine diphosphate is a suitable marker of alcoholism. Thiamine diphosphate sensitivity across subjects was 84.1%, specificity was 85.4%, positive predictive value was 82.4%, and negative predictive value was 88.0%. NIAAA Glossary Terms:  AOD withdrawal syndrome, AOD dependence, thiamine, esters, diagnosis, symptom severity, erythrocyte, phosphates, biochemical markers, specificity and sensitivity of measurement, predictive factor, human study

Marina Perfumi, Laura Mattioli, Laura Forti, Maurizio Massi, and Roberto Ciccocioppo.  Effect of Hypericum perforatum CO₂ extract on the motivational properties of ethanol in alcohol-preferring rats.  Alcohol and Alcoholism 40(4):291-296, July/August 2005.

Summary: Extracts of Hypericum perforatum (HPE; St. John's wort) reduce voluntary ethanol intake in different alcohol-preferring rat lines. This study evaluated the effect of the intragastric (IG) administration of a CO2 HPE extract (HPCO2) on operant ethanol self-administration, as well as on voluntary ethanol intake, after a period of ethanol deprivation in Marchigian Sardinian alcohol-preferring rats. HPCO2 was administered through an indwelling IG catheter 1 hour before the tests. For the self-administration experiments, the rats were trained to self-administer 10% (v/v) ethanol in 30-minute daily sessions under a fixed ratio 1 reinforcement schedule. HPCO2 was also tested on 0.2% w/v saccharin self-administration. For the ethanol deprivation experiments, rats that had a previous experience with voluntary ethanol drinking were deprived of ethanol for 9 days, with water and food freely available; HPCO2 was given by IG injection 1 hour before re-presentation of ethanol. HPCO2 in doses of 31 or 125 mg/kg but not 7 mg/kg, significantly reduced ethanol self-administration, but had no effect on saccharin self-administration. The same doses of the extract abolished the increased ethanol intake following ethanol deprivation. The results provide evidence that HPCO2 markedly reduces the reinforcing properties of ethanol in the self-administration paradigm, as well as the increase of ethanol intake following ethanol deprivation. These findings further support the view that the use of HPE may represent an interesting pharmacological approach in the treatment of alcohol abuse and alcoholism. NIAAA Glossary Terms:  herbal therapy, antidepressants, animal selectively bred for alcohol preference, laboratory rat, intragastric administration, self-administration of drugs, saccharin, AOD abuse, AOD dependence, drug therapy, animal study

Yong-Kyu Lee, Sung-Woo Park, Young-Kyung Kim, Dai-Jin Kim, Jaeseung Jeong, Hugh Myrick, and Young-Hoon Kim.  Effects of naltrexone on the ethanol-induced changes in the rat central dopaminergic system.  Alcohol and Alcoholism 40(4):297-301, July/August 2005.

Summary: The opioid antagonist naltrexone may reduce ethanol reward, but the underlying neurochemical mechanisms have not been clarified. The afferent projections to the nucleus accumbens from the ventral tegmental area (VTA) provide a potential substrate by which endogenous opioids may modulate the dopaminergic rewarding effects of ethanol. The authors assessed messenger ribonucleic acid (mRNA) levels of tyrosine hydroxylase (TH), a major regulatory enzyme in  dopamine synthesis and levels of dopamine and its metabolites, after chronic ethanol administration with and without naltrexone. Sprague-Dawley rats were exposed for 4 weeks to 5% ethanol consumption with and without concurrent naltrexone administration. Levels of TH mRNA in the VTA and substantia nigra (SN) were measured by in situ hybridization, and dopamine and its metabolites in the striatum were measured by high performance liquid chromatography. Chronic ethanol consumption increased TH mRNA levels in the VTA, but produced no significant change in the SN. With naltrexone treatment, ethanol-induced increase in the TH mRNA level was reduced in the VTA. Chronic ethanol consumption did not cause any change in the levels of dopamine and its metabolites in most brain regions. Ethanol consumption with naltrexone treatment significantly increased dopamine level only in the striatum. The results support the presence of interactions of opioid and dopaminergic systems in the VTA in mediating ethanol reward. Thus naltrexone attenuates the ethanol's rewarding properties by interfering with ethanol-induced stimulation of the mesolimbic dopaminergic pathway. NIAAA Glossary Terms:  naltrexone, opioid receptors, antagonists, endogenous opioids, mRNA, tyrosine, hydroxylases, dopamine, neurotransmitter metabolism, laboratory rat, ethanol, ventral tegmental area, corpus striatum, high pressure liquid chromatography, chronic AODE, dopaminergic neuron, brain reward pathway, mesolimbic system, animal study

I. Pelc, C. Hanak, I. Baert, C. Houtain, P. Lehert, F. Landron, and P. Verbanck.  Effect of community nurse follow-up when treating alcohol dependence with acamprosate.  Alcohol and Alcoholism 40(4):302-307, July/August 2005.

Summary: This study measured the effect of community nurse follow-up on abstinence and retention rates in alcohol-dependent outpatients treated with acamprosate. Recently detoxified alcohol-dependent patients were prescribed acamprosate for 26 weeks and randomized to either physician-only follow-up, or physician plus regular visits from a community nurse. Drinking behavior in the next 26 weeks was assessed at monthly visits to non-blind clinicians. The cumulative abstinence duration proportion (CADP) was significantly longer (P = 0.03) in the subjects who had received community nurse support (0.57) than in those who had not (0.39). In part, this might be an artefact of the higher retention rate among those followed up by the nurse, in that the method of calculating CADP allocates 100% days of drinking for the month before a failed attendance. Differences favoring community nurse follow-up were seen for time to first drink and clinical global impression. It was concluded that for recently detoxified alcohol-dependent patients treated with acamprosate, follow-up by a community nurse improves patient retention and probably the 6-month drinking outcome. NIAAA Glossary Terms:  AOD dependence, detoxification, outpatient care, nurse, calcium acetylhomotaurinate, randomized controlled trial, AOD use behavior, AOD abstinence, follow-up study, patient compliance, relapse prevention, human study

Martin Driessen, Wolfgang Lange, Klaus Junghanns, and Tilman Wetterling.  Proposal of a comprehensive clinical typology of alcohol withdrawal — a cluster analysis approach.  Alcohol and Alcoholism 40(4):308-313, July/August 2005.

Summary: The various courses of alcohol withdrawal were characterized by applying the Alcohol Withdrawal Scale (AWS) was applied to alcohol-dependent patients (N = 217) every 4 hours until withdrawal symptoms had passed (four consecutive scores below 3). Patients were medicated by a standardized treatment scheme according to AWS-scores. Hierarchical cluster analysis and discriminant analysis were applied. Five clusters were identified representing increasing alcohol withdrawal severity. Each cluster is characterized by a combination of the two maximum subscores (vegetative and psychopathological subscore) and three additional psychopathological symptoms (anxiety, disorientation, and hallucination). In 18.4% of the patients, relevant symptoms were not observed (cluster 1), 18.9% developed mild or moderate vegetative symptoms only (cluster 2), and 40.6% additional anxiety (cluster 3). In cluster 4 (11.1%) the most frequent psychopathological symptoms were disorientation and anxiety but no hallucinations, which could be observed only in cluster 5 (11.1%). Discriminant analysis using the maximum subscores at the first day of treatment as independent variables correctly predicted 89.9% of the five clusters. The results support a model of alcohol withdrawal clustering along the two dimensions of vegetative and psychopathological severity. Furthermore, the AWS may be useful for predicting the course of alcohol withdrawal on the first day of treatment. NIAAA Glossary Terms:  AOD withdrawal syndrome, AOD dependence, symptom severity, cluster analysis, discriminant analysis, anxiety, AODR hallucinosis, predictive factor, variable, characteristic, factor, human study

Carla de Bruijn, Wim van den Brink, Ron de Graaf, and Wilma A. M. Vollebergh.  The craving withdrawal model for alcoholism: Towards the DSM-V. Improving the discriminant validity of alcohol use disorder diagnosis.  Alcohol and Alcoholism 40(4):314-322, July/August 2005.

Summary: The discriminant validity of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Classification of Diseases (ICD-10) classification of alcohol use disorders (AUD) was compared with that of the Craving Withdrawal Model (CWM). The CWM is an alternative classification that requires craving and withdrawal for the diagnosis of alcohol dependence and raises the alcohol abuse threshold to two DSM-IV AUD criteria. Data were derived from The Netherlands Mental Health Survey and Incidence Study, a large representative sample of the general Dutch population. Only non-abstinent subjects (N = 6041) were included in the present study. The DSM-IV, ICD-10, and CWM were compared using the following discriminant variables: alcohol intake, psychiatric comorbidity, functional status, familial alcohol problems, and treatment sought. The year prevalence of CWM alcohol dependence was lower than the prevalence of ICD-10 and DSM-IV dependence (0.3% versuss 1.4% and 1.4%). The year prevalence of abuse was similar for CWM and DSM-IV (4.7% and 4.9%), but lower for ICD-10 harmful use (1.7%). DSM-IV discriminated poorly between normality and abuse and ICD-10 discriminated poorly between harmful use and dependence. In contrast, the CWM distinctions between normality and abuse, and between abuse, and dependence were significant for most of the discriminant variables. The results indicate that CWM improves the discriminant validity of AUD diagnoses. The predictive validity of the CWM for alcohol and other substance use disorders remain to be studied. NIAAA Glossary Terms:  discriminant validity, diagnostic criteria, alcohol use disorder classification, AOD abuse, AOD dependence, comparative study, AOD intake per occasion, mental health, comorbidity, family AODU history, familial alcoholism, prevalence, survey, human study

Enrique Echeburúa, Ricardo Bravo de Medina, and Javier Aizpiri.  Alcoholism and personality disorders: An exploratory study.  Alcohol and Alcoholism 40(4):323-326, July/August 2005.

Summary: The International Personality Disorder Examination and the Millon Clinical Multiaxial Inventory-II for personality disorders were used to identify the most frequent personality disorders related to alcohol dependence. Consecutively recruited alcohol-dependent patients (n = 30) attending an outpatient clinic were compared with consecutively recruited psychiatric patients with non-addictive disorders (n = 30) and subjects from the general population (n = 31) who matched the patient samples on age, gender, and socioeconomic level. At least one personality disorder was found in 40% of the alcohol-dependent patients and 16.6% of the general clinical sample, compared to 6.4% of the normative sample. Dependent personality disorders were most prevalent (13.3%), followed by paranoid and obsessive-compulsive personality disorders (10% each). NIAAA Glossary Terms:  AOD dependence, personality disorder, obsessive-compulsive disorder, disorder classification, AODR disorder, case-control study, prevalence, AODR paranoia, human study

Charles P. M. Webb, Evelyn J. Bromet, Semyon Gluzman, Nathan L. Tintle, Joseph E. Schwartz, Stanislav Kostyuchenko, and Johan M. Havenaar.  Epidemiology of heavy alcohol use in ukraine: Findings from the world mental health survey.  Alcohol and Alcoholism 40(4):327-335, July/August 2005.

Summary: Data from the World Mental Health (WMH) Survey were used to study the epidemiology of heavy alcohol use in Ukraine. The WMH Composite International Diagnostic Interview was administered in 2002 to a national probability sample of Ukrainian adults (N = 4,725). An algorithm for classifying past-year heavy alcohol use was developed from self-reports about the quantity and frequency of drinking, and its convergent validity was demonstrated. Prevalences and sociodemographic risk factors were examined separately for men and women. The 12-month rates of heavy alcohol use were 38.7% in men and 8.5% in women (22.0% overall). Among heavy alcohol users, 92% of men and 52% of women consumed at least 80 g of ethanol in a typical drinking day on a monthly basis in the year before the interview. The most significant risk factors in men and women were age (26–54 years for men; 18–25 years for women), living in the Southeast region, being in the labor force whether employed or unemployed, and for men, low education and being the father of a young child. For both sexes, a highly significant linear relationship was found between number of risk factors and heavy alcohol use. The rates for men were similar to those reported in a Russian national survey except for Southeast Ukraine where the rate was over 10% higher. The highest rates were among men who were middle-aged, fathers, and unemployed. Future prospective studies are needed to assess the impact of heavy alcohol use on Ukrainian physical health, mental health, and occupational and social functioning. NIAAA Glossary Terms:  heavy AOD use, Ukraine, prevalence, risk factors, demographic characteristics, AOD use pattern, AOD use frequency, AOD intake per occasion, gender differences, regional differences, educational level achieved, employed, unemployed, correlation analysis, risk factors, international differences, Russia, age differences, survey, human study

N. Signorini-Allibe, B. Gonthier, F. Lamarche, H. Eysseric, and L. Barret.  Chronic consumption of ethanol leads to substantial cell damage in cultured rat astrocytes in conditions promoting acetaldehyde accumulation.  Alcohol and Alcoholism 40(3):163-171, May/June 2005.

Summary: The cerebral cytotoxicity of ethanol was compared with that of its main metabolite acetaldehyde after acute or chronic exposures of rat astrocytes in primary culture. Cytotoxicity was evaluated as reduced cell viability (MTT reduction test) and deoxyribonucleic acid (DNA) damage (characterized by single cell gel electrophoresis. Changes in astrocyte survival and DNA integrity only occurred when the astrocytes were chronically exposed to ethanol (20 mM; 3, 6, or 9 days). In contrast, acute exposure to acetaldehyde strongly affected both viability and DNA integrity in a concentration-dependent manner. The cytotoxic effect of acetaldehyde was also indirectly evaluated after modifications of the normal ethanol metabolism by the use of different inducers or inhibitors. In presence of ethanol, the concomitant induction of catalase (by glucose oxidase) and inhibition of aldehyde dehydrogenase (by methylene blue) led to acetaldehyde accumulation within cells, which was followed by reduced viability and a substantial increase in DNA strand breaks. These results are consistent with a possible major role of acetaldehyde during brain ethanol metabolism. On the other hand, the effects observed after N-acetyl-5-methoxytryptamine (AMT; melatonin) could also suggest a possible direct ethanol effect and a role for free radical attacks. The results are thus consistent with a possible predominant role of acetaldehyde during brain ethanol metabolism. On the other hand, the effects observed after AMT could also suggest a possible direct ethanol effect and a role for free radical attacks. NIAAA Glossary Terms:  cytotoxicity, ethanol, acetaldehyde, cerebrum, astrocyte, cell culture study, cultured cell line, electrophoresis, DNA,  cell function, chronic AODE, acute AODE, ethanol metabolism, enzyme inhibitors, inducible enzymes, catalase, aldehyde dehydrogenases, antioxidants, melatonin, free radicals, oxidative stress, dose-response relationship, laboratory study

Youqing Xu, Maria A. Leo, and Charles S. Lieber.  DLPC attenuates alcohol-induced cytotoxicity in HepG2 cells expressing CYP2E1.  Alcohol and Alcoholism 40(3):172-175, May/June 2005.

Summary: This study examined  whether oxidative stress generated by ethanol metabolism via cytochrome P450 2E1 (CYP2E1) could be overcome by using dilinoleoylphosphatidylcholine (DLPC), a harmless antioxidant extracted from soybeans. The question was addressed by determining whether DLPC protects against alcohol-induced cytotoxicity in HepG2 cells expressing CYP2E1. A HepG2 subclone (2E1) expressing CYP2E1 and a control subclone (Neo) were exposed for 2 hours to DLPC (10 µM). Ethanol (100 mM) was then added for 5 days. Ethanol significantly decreased cell viability in the 2E1 cells and increased apoptosis. DLPC attenuated these alterations, with the most significant effects in the 2E1 cells. This was accompanied by a reduction of ethanol-induced oxidative stress, including lower hydrogen peroxide production in the 2E1 cells, but not in the Neo cells. The mitochondrial membrane potential was significantly diminished by ethanol in both cells and was also improved after adding DLPC, but only in the 2E1 cells. Mitochondrial glutathione (GSH) was also partially restored in the 2E1 cells by DLPC, which significantly inhibited CYP2E1 induction by ethanol. Thus DLPC opposes the cytotoxicity induced by alcohol in HepG2 cells expressing CYP2E1, a protective action due, at least in part, to attenuation of alcohol-induced oxidative stress and the alteration in the mitochondrial membrane potential. Based on these beneficial effects of DLPC and its harmlessness, the authors suggest that its therapeutic action be tested in alcoholics. NIAAA Glossary Terms:  ethanol metabolism, cytochrome P450 2E1, antioxidants, cytotoxicity, cell culture study, cultured cell line, alcoholic liver disorder, apoptosis, oxidative stress, peroxide, mitochondria, glutathione, inducible enzymes, protective drug effect, AOD dependence, laboratory study

Kyoko Miyasaka, Hiroko Hosoya, Saeko Takano, Minoru Ohta, Ayako Sekime, Setsuko Kanai, Toshimitsu Matsui, and Akihiro Funakoshi.  Differences in ethanol ingestion between cholecystokinin-A receptor deficient and -B receptor deficient mice.  Alcohol and Alcoholism 40(3):176-180, May/June 2005.

Summary: Cholecystokinin (CCK) modulates dopamine (DA) release in the nucleus accumbens (NA) through the CCK-A receptor (CCK-AR). The dopaminergic neurotransmission between the ventral tegmental area and the limbic forebrain is a critical neurobiological component of alcohol and drug self-administration. Based on the evidence of interaction between CCK and DA, the authors had found previously that the CCK-AR gene –81A/G polymorphism was associated with alcohol dependence. Since the precise mechanism underlying this association has not been elucidated, the authors examined the role of CCK-AR in ethanol ingestion by comparing CCK-AR gene-deficient (CCK-AR–/–) mice with CCK-BR–/– and wild-type mice. The two-bottle choice protocol was conducted and the righting reflex was examined in these three genotypes. The protein level of dopamine 2 receptor (D2R) in the NA was determined by western blotting. CCK-AR–/– mice consumed more ethanol than CCK-BR–/– and wild-type mice and showed no aversion to high concentrations of ethanol solution. However, the difference was actually in the total fluid consumption; alcohol preference remained unchanged, indicating that the differences were not specific to alcohol. Behavioral sensitivity to ethanol, examined using the righting reflex, did not differ significantly between the groups. D2R expression in the NA was significantly lower in the CCK-BR–/– mice and significantly higher in CCK-AR–/– mice than in wild-type mice. The difference in voluntary ethanol ingestion between CCK-AR–/– and CCK-BR–/– mice might be attributable in part to the different levels of D2R expression in the NA. NIAAA Glossary Terms:  ethanol, cholecystokinin, dopamine, nucleus accumbens, dopaminergic receptors, genetic polymorphism, gene knockout technology, genotype, controlled study, animal behavior, righting reflex, laboratory mice, animal study

Isabel J. Pastor, Francisco Javier Laso, Alfonso Romero, and Rogelio González-Sarmiento.  Interleukin-1 gene cluster polymorphisms and alcoholism in Spanish men.  Alcohol and Alcoholism 40(3):181-186, May/June 2005.

Summary: Different genes, including those encoding inflammatory cytokines, have been analyzed in an attempt to explain differences in susceptibility to alcoholism and alcoholic liver disease (ALD). Thus it has been reported recently that both the interleukin 1 receptor antagonist (IL1RN) and the IL1ß (IL1B) genes may influence the risk of ALD in Japanese alcoholics. The authors of this study analyzed the distribution of single nucleotide polymorphisms (SNPs) located in the IL1A, IL1B, IL1R1, and IL1RN genes in alcoholic and nonalcoholic Spanish men. Deoxyribonucleic acid samples were obtained from 139 male alcoholics, 78 of whom were diagnosed as alcohol dependent (32 patients with cirrhosis and 46 without ALD) and 61 as alcohol abusers (25 with cirrhosis and 36 without ALD). The controls were 81 age- and sex-matched healthy volunteers. Alleles –511 IL1B*1 and IL1RN*1 were found more frequently in alcoholic patients than in the control group. No association of alcoholism or ALD with polymorphisms in the IL1A and IL1R1 genes was found. It was concluded that the proteins encoded by the IL1RN and IL1B genes may be involved in susceptibility to alcoholism in Spanish men, probably through a different pathway from that involved in the regulation of the inflammatory response. NIAAA Glossary Terms:  inflammation, cytokines, AOD dependence, alcoholic liver disorder, alcoholic liver cirrhosis, antagonists, interleukin-1, risk factors, genetic polymorphism, genetic correlation analysis, controlled study, allele, gene frequency, human study

Andreas Franke, Inaam A. Nakchbandi, Alexander Schneider, Hermann Harder, and Manfred V. Singer. The effect of ethanol and alcoholic beverages on gastric emptying of solid meals in humans.  Alcohol and Alcoholism 40(3):187-193, May/June 2005.

Summary: The study examined the effect of pure ethanol, alcoholic beverages, and their non-alcoholic components on gastric emptying of solid meals in humans. Fasting healthy male subjects (N = 16) received 300 ml of the following solutions in random order once a week: 4% and 10% (v/v) ethanol, beer, red wine, 5.5% and 11.4% (w/v) glucose, and water. The test solutions were given either together with a low-calorie (270 kcal, n = 8) or a high-calorie (740 kcal, n = 8) solid meal. Gastric emptying was determined by ultrasonography of the antrum. Gastric half-emptying time (t½) of the high caloric solid meal with water was 131.3 ± 7 minutes. The ingestion of 4% and 10% ethanol (t½ = 158.8 ± 9.3 and 165.6 ± 6.2 minutes respectively), beer (t½ = 163.1 ± 11 minutes), and red wine (t½ = 186.3 ± 8.4 minutes) resulted in a significantly longer t½ than water. The lag phases after 4% and 10% ethanol, beer, and red wine were not significantly different from that of water (48.1 ± 6.5 minutes). Compared with water, ingestion of 5.5% and 11.4% glucose resulted in a significantly longer t½ (153.8 ± 5 and 168.1 ± 14.4 minutes respectively) by increasing the duration of the lag phase. The high-calorie meals resulted in a doubling of t½ when compared with the low-calorie meals. The effect of the solutions on the gastric emptying times, however, was similar for both test meals. The results led to the following conclusions: (1) ethanol in low concentrations (4% and 10%) prolongs gastric emptying of solid meals; this inhibitory effect is not dose-dependent; (2) alcoholic beverages (beer and red wine) also prolong gastric emptying; the inhibitory effect of red wine, but not of beer, is more pronounced than that of the corresponding ethanol concentration and amount; (3) the inhibitory effect of ethanol and alcoholic beverages is mainly induced by prolongation of the gastric emptying phase (without affecting the lag phase), whereas glucose (5.5% and 11.4%) prolongs the lag phase in a dose-dependent manner; (4) the inhibitory effect of ethanol, beer, and red wine on gastric emptying does not depend on the caloric content of the meal. NIAAA Glossary Terms:  digestion, stomach emptying, ethanol, beer, red wine, water, glucose, caloric value, dose-response relationship, ultrasonography, human study

Lisa C. Caldwell, Alecia D. Schweinsburg, Bonnie J. Nagel, Valerie C. Barlett, Sandra A. Brown, and Susan F. Tapert.  Gender and adolescent alcohol use disorders on BOLD (blood oxygen level dependent) response to spatial working memory.  Alcohol and Alcoholism 40(3):194-200, May/June 2005.

Summary: The objective was to determine how alcohol use differentially affects brain functioning in male and female adolescents. Adolescents with alcohol use disorders (AUDs; 7 females, 11 males) and control adolescents without AUDs (9 females, 12 males), aged 14–17 years, performed spatial working memory and vigilance tasks during functional magnetic resonance imaging. Gender, AUD, and their interaction were significantly associated with brain activation patterns to the tasks. There were interactions in the superior frontal, superior temporal, cingulate, and fusiform regions, in which females and males with AUDs showed a different brain response from each other and control subjects. Overall, female adolescents with AUDs showed a greater departure from normal activation patterns than male adolescents with AUD. Thus adolescent alcohol involvement may affect male and female brains differently, and adolescent females may be somewhat more vulnerable to adverse alcohol effects. With continued drinking, these adolescents may be at increased risk for behavioral deficits. NIAAA Glossary Terms:  ethanol, underage AOD use, brain function, adolescent, gender differences, alcohol use disorder classification, controlled study, spatial memory, attention, magnetic resonance imaging, behavioral problem, human study

J.E. Yonker, L.-G. Nilsson, Agneta Herlitz, and R.M. Anthenelli.  Sex differences in spatial visualization and episodic memory as a function of alcohol consumption.  Alcohol and Alcoholism 40(3):201-207, May/June 2005.

Summary: Sex differences in visuospatial ability and in episodic memory have been reliably demonstrated, and studies of alcoholics have consistently documented cognitive deficits in visuospatial ability, problem solving, and memory function. This cross-sectional, population-based study examined whether sex differences in cognitive performance are affected by alcohol consumption. Drinking data were collected from 2,224 randomly sampled adults, aged between 35 and 85 years, who participated in the Betula study on memory, health, and aging. Participants were classified into non-drinking and light, moderate, and heavy drinking subgroups based on sex-adjusted normative values. Cognitive tasks demonstrating clear sex differences, such as episodic memory tasks (favoring women) and spatial visualization tasks (favoring men), were conducted and performance was assessed by sex and by drinking group. After controlling for age and education, overall analyses found expected sex differences in episodic memory and spatial visualization. When these sex differences were examined by drinking group, visuospatial performance favoring men disappeared for the moderate to heavy drinking groups, but higher performance by women on episodic memory tasks was consistent across all alcohol consumption levels. Traditional biomarkers of increased alcohol consumption (gamma-glutamyl transferase and mean corpuscular volume) correlated with the reported drinks/day. The results support the theory that moderate alcohol intake may benefit cognitive function in women, but not necessarily in men. NIAAA Glossary Terms:  cross-sectional study, gender differences, cognitive ability, AOD consumption, AOD nonuse, light AOD use, moderate AOD use, heavy AOD use, controlled study, random sample, spatial processing impairment, memory, AODR biological markers, gamma glutamyl transferase, mean corpuscular volume, correlation analysis, human study

Andrea Canagasaby and Daniel C. Vinson.  Screening for hazardous or harmful drinking using one or two quantity–frequency questions.  Alcohol and Alcoholism 40(3):208-213, May/June 2005.

Summary: The accuracy of quantity-frequency (QF) questions in screening for hazardous or harmful drinking was evaluated based on interviews with three groups: patients presenting to emergency departments for care of an acute injury (n = 1,537) or a medical illness (n = 1,151), and community controls interviewed by telephone (n = 1,112). The first question about alcohol was a single alcohol screening question (SASQ), ‘When was the last time you had more than X drinks in one day?’, where X = 4 for women and 5 for men, with any time in the past 3 months considered a positive screen (1 drink = 14 g ethanol). The subsequent alcohol questions were a calendar-based review of recent drinking and the alcohol questions from the Diagnostic Interview Schedule, which included questions about usual frequency and average quantity. Hazardous drinking was defined as drinking >4 drinks in a day or >14 drinks in a week for men (3 and 7 for women). Standard diagnostic criteria were used to define current alcohol use disorders. The areas under the receiver operating characteristic (ROC) curves in identifying hazardous drinking or current alcohol use disorder were compared. The area under the ROC curves in the three samples combined were 0.81 for SASQ (95% confidence interval [CI], 0.79–0.82), 0.80 for a question about average quantity alone (0.79–0.82), and 0.85 for the product of usual frequency times average quantity (0.84–0.86). The QF product and the question about average quantity performed consistently across the three groups. One way to put these findings into practice in clinical settings is to screen first with a single question, such as the SASQ, a single question about typical quantity, or a question about the frequency of heavy drinking such as the third item of the Alcohol Use Disorders Identification Test (AUDIT). NIAAA Glossary Terms:  alcohol quantity-frequency methods, evaluation study, emergency care, AODR injury, AODR disorder, AOD use screening method, questionnaire, heavy AOD use, alcohol use test, human study

Adam Bisaga, Michael Laposata, Shan Xie, and Suzette M. Evans.  Comparison of serum fatty acid ethyl esters and urinary 5-hydroxytryptophol as biochemical markers of recent ethanol consumption.  Alcohol and Alcoholism 40(3):214-218, May/June 2005.

Summary: The effects of an acute dose of ethanol on serum fatty acid ethyl esters (FAEE) concentration and urinary 5-hydroxytryptophol (5-HTOL)/5-hydroxyindole-3-acetic acid (5-HIAA) ratio were examined in heavy drinkers (N = 16; 14 males) who were tested in a single, 2-day long session. Six participants received 1.5 g/l of ethanol/l of body water (~0.75 g/kg of body weight, low dose [LD] group) and 10 participants received 2.0 g/l of ethanol (~1.0 g/kg of body weight, high dose [HD] group) in four divided doses every 20 minutes. Blood, urine, and breath samples were collected repeatedly over 36 hours following the ingestion of ethanol and analyzed for the presence of FAEE (blood), 5-HTOL/5-HIAA (urine), and ethanol (breath). Serum gamma-glutamyltransferase (GGT), a marker of chronic ethanol use, was also measured. The breath ethanol level peaked ~1 hour after the last dose, at 95 and 120 mg/dl for the LD and HD groups respectively. The mean urinary 5-HTOL/5-HIAA ratio was significantly elevated 5 and 9 hours after ethanol administration, but returned to baseline at 13 hours. This ratio was twice as high in the HD group compared with the LD group. Serum FAEE levels were significantly elevated at 5 hours after ethanol administration, but not at 13 hours. There were no time-dependent changes in serum GGT levels. It was concluded that measuring FAEE levels and the 5-HTOL/5-HIAA ratio provides a convenient method to detect recent ethanol use, particularly binge drinking. However, the applicability of these measures in detecting ethanol use may be limited in traditional clinical trial settings. NIAAA Glossary Terms:  fatty acid ethyl esters, hydroxytryptophol, hydroxyindoleacetic acid, breath alcohol analysis, heavy AOD use, ethanol, acute AODE, chronic AODE, blood, urine, gamma glutamyl transferase, AODR biological markers, dose-response relationship, binge AOD use, comparative study, human study

M.J. Emmen, G. M. Schippers, H. Wollersheim, and G. Bleijenberg.  Adding psychologist's intervention to physicians' advice to problem drinkers in the outpatient clinic.  Alcohol and Alcoholism 40(3):219-226, May/June 2005.

Summary: The effectiveness of a brief psychological intervention for problem drinking was tested among outpatients in a hospital setting. Over a period of 3 years patients who visited an outpatient clinic for general internal medicine were screened by physicians for problem drinking. Of the 4,728 patients screened, 284 (6%) scored positive on problem drinking. The problem drinkers who participated in the intervention study (N = 123) received a computerized baseline assessment and were randomly allocated to a brief psychosocial intervention given by a psychologist (the Dutch version of W.R. Millers' Drinker's Check-Up) (n = 61) or to ‘care as usual’ (n = 62) and were followed-up at 6 months. The outcome measures were alcohol consumption and increased motivation to reduce alcohol consumption. Most patients reduced their alcohol consumption over time, but no differences were found between the intervention and control groups. A slightly, but not significantly, larger proportion of patients who received the intervention increased their motivation to change. No conclusive evidence was found for the effectiveness of adding a brief psychological intervention to the physician's advice for problem drinking among outpatients in a hospital setting. NIAAA Glossary Terms:  brief intervention, psychosocial treatment method, outpatient care, problematic AOD use, follow-up study, treatment outcome, AOD consumption, motivation, controlled study, human study

G. Rubio, G. Ponce, R. Rodriguez-Jiménez, M.A. Jiménez-Arriero, J. Hoenicka, and T. Palomo.  Clinical predictors of response to naltrexone in alcoholic patients: Who benefits most from treatment with naltrexone?  Alcohol and Alcoholism 40(3):227-233, May/June 2005.

Summary: The objective was to determine the clinically ascertained variables that are related to satisfactory response to naltrexone treatment of alcohol dependence after detoxification. Intake and outcome variables were measured in a randomized 3-month open-controlled trial (N = 336 males) comparing the effects of naltrexone plus psychotherapy treatment versus psychotherapy treatment alone on the maintenance of abstinence in the final 28 days. Predictors of a positive response to naltrexone treatment were family history of alcoholism (p = 0.010), early age at onset of drinking problems (p = 0.014), and comorbid use of other drugs of abuse (p < 0.001). Among the subjects not treated with naltrexone, a greater number of predictor variables was associated with lower final 28 days abstinence rates (p = 0.00003), but this was not the case in patients treated with naltrexone (p = 0.844). Patients with these features, suggesting biological vulnerability, overall have poorer outcomes, but they can be improved with naltrexone treatment. The type of alcoholism should be considered before deciding on the pharmacological strategy. NIAAA Glossary Terms:  naltrexone, psychotherapy, drug therapy, combined modality therapy, treatment outcome, AOD dependence, predictive factor, familial alcoholism, early disease onset, comorbidity, multiple drug use, controlled study, randomized controlled trial, clinical trial, AOD abstinence, human study

Anthony P. Polednak.  Recent trends in incidence rates for selected alcohol-related cancers in the United States.  Alcohol and Alcoholism 40(3):234-238, May/June 2005.

Summary: Data from cancer registries were used to analyze recent incidence trends for cancer types most strongly associated with alcohol use. Age-standardized annual incidence data for squamous cell carcinomas of the oral cavity and pharynx, esophagus, and larynx diagnosed in the most recent 10-year period (1992–2001) were examined for geographic areas included in the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program of high-quality cancer registries. For all geographic areas combined, incidence levels for these cancers declined over time, with no evidence of a recent plateau or upturn. This also held true for younger adults (20–54 years old at diagnosis). For white males, declines in incidence occurred in each of the 11 geographic areas and were statistically significant in 9. The declines in incidence were consistent with temporal declines in apparent alcohol consumption by state, although the prevalence of binge and heavy drinking in adults increased in some states. Although there was no evidence of a recent plateau in incidence, continued surveillance is needed in view of recent increases in the prevalence of binge and heavy drinking among US adults. NIAAA Glossary Terms:  incidence, cancer, time series analysis, trend, AODR disorder, AOD consumption, prevalence, binge AOD use, heavy AOD use, squamous cell carcinoma, mouth, oral disorder, pharynx, esophageal disorder, larynx, epidemiology, epidemiological indicators, human study

Kerry S. O'Brien, Joshua M. Blackie, and John A. Hunter.  Hazardous drinking in elite New Zealand sportspeople.  Alcohol and Alcoholism 40(3):239-241, May/June 2005.

Summary: The link between hazardous drinking and level of participation in sports was examined in university students in New Zealand. Sports science and general university students (N = 427) completed a sporting profile questionnaire that included the Alcohol Use Disorders Identification Test (AUDIT).  Elite athletes (both provincial and international/country level) reported higher rates of hazardous drinking than non-athletes and non-elite athletes. Similar differences were observed in AUDIT subscale scores, with international/country level athletes reporting greater symptoms of alcohol dependence than other groups. NIAAA Glossary Terms:  sports, heavy AOD use, AODU by athlete, undergraduate student, controlled study, New Zealand, survey, questionnaire, symptom, AOD dependence, human study

Aafje Dotinga, Regina J.J.M. Van Den Eijnden, Willem Bosveld, and Henk F. L. Garretsen.  The effect of data collection mode and ethnicity of interviewer on response rates and self-reported alcohol use among Turks and Moroccans in The Netherlands: An experimental study.  Alcohol and Alcoholism 40(3):242-248, May/June 2005.

Summary: This study tested the effects of data collection method and interviewer ethnicity on response rates and self-reported alcohol use among second-generation Turks and Moroccans in Rotterdam, The Netherlands. Personal interviews were administered to 269 Turks and 271 Moroccans, and 475 Turks and 482 Moroccans received a mailed questionnaire. Half of the Turks and Moroccans randomly allocated to the interview mode were ethnically matched to the interviewer; the remainder were allocated to a Dutch interviewer. Turks and Moroccans more often responded to a personal interview than to a mailed questionnaire. Ethnicity of the interviewer had no effect on response rates. Turks and Moroccans tended to report higher alcohol use and reported significantly more frequent excessive drinking in the mailed survey than in the personal interview. Both groups reported a higher prevalence of alcohol use during the previous 6 months when interviewed by a Dutch interviewer compared with an ethnically matched interviewer. Thus mail surveys seem most suitable for measuring mean and excessive alcohol use among second-generation Turks and Moroccans. NIAAA Glossary Terms:  AOD use, AOD consumption, prevalence, self report, data collection, ethnic group, ethnic differences, Morocco, Turkey, Netherlands, interview, questionnaire, comparative study, cultural sensitivity, human study

Jan Van Den Bulck and Kathleen Beullens.  Television and music video exposure and adolescent alcohol use while going out.  Alcohol and Alcoholism 40(3):249-253, May/June 2005.

Summary: This study examined whether television viewing and exposure to music videos predict alcohol consumption by high school students when they go out. Data were collected in February 2003 (t1) and February 2004 (t2) from a random sample of first- and fourth-year secondary school children (N = 1,648) of Flanders, Belgium. Self-reported general TV viewing and music video exposure at t1 and the quantity of alcohol consumed while going out at t2 were measured. Controls were gender, age group, smoking behavior, and alcohol use (at t1) and pubertal status (at t2). Overall television viewing per day and music television viewing at t1 significantly predicted the amount of alcoholic beverages adolescents consumed while going out at t2. These results remained significant after controlling for alcohol use at t1, gender, smoking, and pubertal status. TV viewing habits are a significant predictor of alcohol consumption while going out. TV viewing might cause an increase in alcohol consumption or it might be an early symptom of developing alcohol habits. NIAAA Glossary Terms:  high school student, adolescent, underage drinking, AOD consumption, predictive factor, television, popular culture, Belgium, self report, puberty, controlled study, human study

Steven Rosenzweig Haugbøl, Bjarke Ebert, and Jakob Ulrichsen.  Upregulation of glutamate receptor subtypes during alcohol withdrawal in rats.  Alcohol & Alcoholism 40(2):89-95, March/April 2005.

Summary: To investigate glutamate receptor subtypes during alcohol withdrawal, rats were exposed to severe ethanol intoxication for 84 hours (intragastric intubation of ethanol five times a day) then decapitated at 0, 12 and 36 hours after the last dose (n = 7 rats per group). The densities of N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors were studied in membranes from the forebrain by using the (tritium-labeled) specific ligands MK-801 and AMPA respectively. Although no change was observed in the maximal density (Bmax) of MK-801 binding sites at the time of withdrawal, MK-801 binding was increased by 49% 12 hours into the withdrawal reaction compared with the control group and was still increased by 24% (not statistically significant) at 36 hours. No significant alteration in the Bmax of AMPA binding was detected at the time of withdrawal from chronic ethanol intoxication, but 12 hours into withdrawal AMPA binding was markedly increased by 94%. At 36 hours post alcohol AMPA binding had returned to control levels. No significant alteration in the dissociation constant (KD) of either MK-801 or AMPA binding was observed at any time. It was concluded that NMDA and AMPA receptors are involved in the cerebral hyperactivity of alcohol withdrawal. NIAAA Glossary Terms:  glutamate receptors, NMDA receptors, forebrain, cerebrum, receptor ligand binding, tritium, ethanol, AOD intoxication, AOD dependence, AOD withdrawal syndrome, controlled study, laboratory rat, animal study

Gennadiy Novitskiy, Rajani Ravi, James J. Potter, Lynda Rennie-Tankersley, Lan Wang, and Esteban Mezey.  Effects of acetaldehyde and TNF-α[alpha] on the inhibitory kappa B-α[alpha] protein and nuclear factor kappa B activation in hepatic stellate cells.  Alcohol & Alcoholism 40(2):96-101, March/April 2005.

Summary: Transcription of type I collagen promoters and type I collagen production are enhanced by acetaldehyde and inhibited by tumor necrosis factor-alpha (TNFα). Nuclear factor kappa B (NF-κB), an inhibitor of type I collagen promoters, is increased by both acetaldehyde and TNFα. This study assessed the effects of acetaldehyde in comparison to the effects of TNFα on inhibitory kappa B-α (IκB-α) protein and NF-κB activation in hepatic stellate cells. Activated rat hepatic stellate cells in culture were exposed to acetaldehyde or TNFα for brief periods, after which the cells were harvested for the determination of IκB-α protein, IκB-α kinase activity and nuclear NF-κB. Acetaldehyde increased IκB-α kinase activity and decreased IκB-α after 10 minutes of exposure, with recovery towards control levels at 20 minutes. In contrast, TNFα resulted in higher IκB-α kinase activity at 20 minutes than at 10 minutes, and similar low IκB-α at both times. Both acetaldehyde and TNFα enhanced nuclear NF-κB (p65), but acetaldehyde alone also increased NF-κB (p50). Thus TNFα and acetaldehyde independently activate NF-κB by rapid enhancement of IκB-α kinase activity and degradation of IkB-α protein. Increased TNFα is the principal mechanism for the elevation of NF-κB in severe alcoholic hepatitis. The elevation of NF-κB due to TNFα enhances liver injury, but inhibits fibrogenesis. In contrast, the effect of acetaldehyde in activating NF-κB is associated with increases in both liver injury and fibrogenesis, indicating that the effects of acetaldehyde on fibrogenesis are mediated by cytokines and by trans-acting factors other than NF-κB. NIAAA Glossary Terms:  acetaldehyde, tumor necrosis factor-alpha, cytokines, collagen, hepatic stellate cell, protein kinases, gene expression, alcoholic hepatitis, alcoholic liver disorder, fibrosis, cell culture study

Lars Retterstol, Knut Erik Berge, Øivind Braaten, Lars Eikvar, Terje R. Pedersen, and Leiv Sandvik.  A daily glass of red wine: Does it affect markers of inflammation?  Alcohol & Alcoholism 40(2):102-105, March/April 2005.

Summary: Although epidemiological studies have shown that moderate alcohol consumption is associated with a decreased risk of developing cardiovascular disease, the causal mechanisms are only partly understood. This study tested the hypothesis that the protective effect of red wine is partly mediated through a reduction in inflammation, an important process in the progression of atherosclerosis, in a randomized controlled crossover trial to study the effect of red wine on the levels of the inflammatory markers serum C-reactive protein (CRP) and plasma fibrinogen in healthy subjects (N = 87, mean age 50 years) who were nonsmokers. The subjects were randomized to drink one glass of red wine (150 ml, 15 g alcohol) every day or to undergo a period of total abstention from alcohol. The time on each regimen was 3 weeks. Red wine did not reduce CRP levels and only marginally reduced fibrinogen levels compared with a similar period without alcohol. NIAAA Glossary Terms:  red wine, moderate AOD use, AOD abstinence, atherosclerosis, inflammation, biological markers, fibrinogen, plasma, protective drug effect, protective factors, clinical trial, controlled study, human study

Elzbieta Wrobel, Dominika Skrok-Wolska, Marcin Ziolkowski, Agnieszka Korkosz, Boguslaw Habrat, Bohdan Woronowicz, Andrzej Kukwa, Wojciech Kostowski, Przemyslaw Bienkowski, and Anna Scinska.  Taste responses to monosodium glutamate after alcohol exposure.  Alcohol & Alcoholism 40(2):106-111, March/April 2005.

Summary: The effects of acute and chronic exposure to ethanol on taste responses to monosodium glutamate (MSG) a prototypic umami substance (umami is the Japanese term for a postulated fifth taste in addition to sweet, sour, bitter, and salty), were evaluated in male alcoholics (n = 36) and control subjects (n = 25). The participants rated intensity and pleasantness of MSG taste (0.03–10.0%). The effects of acute exposure of the oral mucosa to ethanol rinse (0.5–4.0%) on MSG taste (0.3–3.0%) were examined in a separate experiment with 10 social drinkers. The alcoholic and control groups did not differ in their ratings of intensity and pleasantness of MSG taste. Electrogustometric thresholds were significantly (p < 0.01) higher (i.e. worse) in the alcoholics, and the difference remained significant after controlling for differences between groups in cigarette smoking and coffee drinking. In social drinkers, oral rinsing with ethanol did not alter either intensity or pleasantness of MSG taste. These findings suggest that neither acute nor chronic alcohol exposure alters taste responses to MSG, and that alcohol dependence may be associated with deficient threshold taste reactivity as assessed by electrogustometry. NIAAA Glossary Terms:  taste perception, sodium glutamate, self report, ethanol, AOD dependence, social AOD use, acute AODE, chronic AODE, specific data collection instrument, subjective variables, controlled study, human study

Marcus Richards, Rebecca Hardy, and Michael E. J. Wadsworth.  Alcohol consumption and midlife cognitive change in the British 1946 birth cohort study.  Alcohol & Alcoholism 40(2):112-117, March/April 2005.

Summary: This study examined the association between self-reported alcohol consumption and change in memory, speed, and concentration in midlife participants of the 1946 British birth cohort (903 men and 861 women) enrolled in the Medical Research Council's National Survey of Health and Development. After controlling for educational attainment, occupational social class, and general cognitive ability, an association was found between alcohol consumption and slower memory decline from ages 43 to 53 years in men. In women, alcohol consumption was associated with a more rapid decline in visual search speed over the same age interval. These effects were not explained by a further control for health status (body water weight, smoking, exercise, cardiorespiratory disease, and affective state). While the findings suggest that alcohol consumption is associated with slower memory decline, the negative association between alcohol and psychomotor function in women is a potential cause for concern. NIAAA Glossary Terms:   middle-aged adult, alcoholic beverage, AOD consumption, cognitive ability, memory, attention, cohort study, longitudinal study, protective factor, gender differences, human study

Annika Jakobsson, Gunnel Hensing, and Fredrik Spak.  Developing a willingness to change: Treatment-seeking processes for people with alcohol problems.  Alcohol & Alcoholism 40(2):118-123, March/April 2005.

Summary: Treatment-seeking processes, particularly promoting and hindering factors, were studied in men and women with alcohol problems. Open interviews were held with 12 individuals (5 women, 7 men) within a month of their first voluntary treatment for alcohol problems. The interview protocols were analyzed consecutively in accordance with grounded theory methodology. The basic psychosocial process that led to treatment-seeking was found to be developing willingness to change. Sub-processes that supported willingness to change were actuating inner forces, dealing with conflicting feelings and thoughts, and hoping to turn the situation around. These processes were continuously assisted by demanding and caring support from partners, friends, or professionals. In conclusion, the processes that preceded treatment-seeking were highly complex, and both internal and external factors promoted and hindered treatment entry. The most striking hindering factors were the social significance of alcohol and grief related to thoughts of abstaining. Such feelings need to be considered when motivating people to seek treatment for alcohol problems. NIAAA Glossary Terms:  problematic AOD use, AOD dependence, AOD abstinence, social benefit of AOD, alcoholic beverage, help-seeking behavior, treatment readiness, treatment factors, social support,  patient psychological history, interview, self report, readiness to change, motivation, human study

Matthias J. Müller, Armin Scheurich, Hermann Wetzel, Armin Szegedi, and Martin Hautzinger.  Sequentially adjusted randomization to force balance in controlled trials with unknown prevalence of covariates: Application to alcoholism research.  Alcohol & Alcoholism 40(2):124-131, March/April 2005.

Summary: Adequate interpretation of treatment outcome studies with small to medium sample sizes (N < 200) requires balancing groups with regard to important factors that sometimes have low prevalence. This study tested a simple procedure for randomizing patients to different treatments in clinical alcoholism research, taking into account relevant background variables. An easily applicable modification of Efron's biased coin method for the randomization of treatments within strata of unknown but low prevalence was compared with the original approach and alternative methods by computer simulation (10,000 runs). The authors provide an application example for a clinical trial in alcoholism research. The sequentially adjusted randomization procedure yielded results similar to Efron's approach without the need to monitor the assignment history throughout the trial. The new method was slightly superior to Efron's approach in randomizing subjects in strata with n ≤ 20, whereas strata with n > 20 favored randomization with Efron's approach. Taking into account all results from simulation, the new approach reached a proportion of acceptable balanced randomization greater than 95% in all stratum sizes. The new method provides three major advantages in clinical trials: (1) it can be easily implemented in any trial without technical equipment; (2) it works with high accuracy in trials with a priori unknown but low numbers of subjects (4 ≤ n ≤ 20) in prognostic relevant strata; and (3) a deterministic assignment tendency is completely avoided, as a random process takes place throughout the assignment procedure. NIAAA Glossary Terms:  randomized controlled trial, clinical trial, treatment research, AOD dependence, reliability (research methods), research and evaluation method, computer technology, intermethod comparison, validation study

Norman Giesbrecht, Anca Ialomiteanu, and Lise Anglin.  Drinking patterns and perspectives on alcohol policy: Results from two Ontario surveys.  Alcohol & Alcoholism 40(2):132-139, March/April 2005.

Summary: Studies often have not examined whether attitudes on alcohol policies vary according to a respondent's drinking pattern. This study examined the association between six drinking variables in survey respondents and their views on six alcohol policy topics. Data were available from two telephone interview surveys in Ontario in 2000 (n = 1,294) and 2002 (n = 1,206) of representative samples of adults, aged 18 and older, selected by random digit dialing. The six drinking variables were drinking status, drinking frequency, usual number of drinks, typical weekly volume, frequency of 5 or more drinks per occasion, and Alcohol Use Disorders Identification Test (AUDIT) scores. The six alcohol policy items examined were alcohol taxes, warning labels, density of retail alcohol outlets, privatization of government liquor stores, alcohol advertising, and consultation with health experts on alcohol policy decisions. Logistic regression analyses included five demographic variables: gender, age, marital status, education, and income. There was strong support among males for increased access to alcohol and fewer controls over alcohol policies. This relationship, although not as strong, also emerged for frequent consumers, high volume drinkers, and those with a higher AUDIT score. The authors concluded that government policies that tend to make alcohol more available cater, whether intentionally or not, to young, heavy-drinking males who possibly experience problems related to their drinking behavior. NIAAA Glossary Terms:  public policy on AOD, AOD use pattern, AOD consumption, AOD intake per occasion, AOD use frequency, heavy AOD use, binge AOD use,  alcohol use test, location and density of AOD outlets, AOD availability, alcoholic beverage sales outlet, sales and excise tax, warning label, AOD product advertising, health care worker, supply reduction policy, survey, interview, random sample, regression analysis, attitude toward AOD, gender differences, age differences, educational level achieved, income, Canada, human study

Diva Eensoo, Marika Paaver, Maarike Harro, and Jaanus Harro.  Predicting drunk driving: Contribution of alcohol use and related problems, traffic behaviour, personality and platelet monoamine oxidase (MAO) activity.  Alcohol & Alcoholism 40(2):140-146, March/April 2005.

Summary: This study evaluated the predictive value for drunk driving of socioeconomic data, alcohol consumption measures, smoking, platelet monoamine oxidase (MAO) activity, traffic behavior habits, and impulsivity measures. Data were collected from male drunk driving offenders (n = 203) and control subjects (n = 211) using self-report questionnaires, and blood samples were obtained from the two groups.  A combination of variables was identified that predicted correctly about 80% of the subjects in the drunk driving and control groups. Among the health-behavior measures, significant independent discriminators in the final model were alcohol-related problems, frequency of using alcohol, the amount of alcohol consumed, and smoking. Predictive traffic behavior measures were seat belt use and paying for parking. Among the impulsivity measures, dysfunctional impulsivity was the best predictor. Platelet MAO activity and age also had an independent predictive value. The results support the view that drunk driving arises from a combination of various behavioral, biological, and personality-related risk factors. NIAAA Glossary Terms:  drinking and driving, AOD intoxication, DWI arrest, predictive factor, risk factors, socioeconomic factors, AOD consumption, AOD use pattern, monoamine oxidase, driver performance, impulsive behavior, controlled study, questionnaire, self report, blood proteins, platelets, health related behavior, AODR markers, AODR biological markers, AOD use frequency, AOD intake per occasion, AOD consumption, smoking, discriminant analysis, seat belt, age differences, human study

Olivier Ameisen.  Complete and prolonged suppression of symptoms and consequences of alcohol-dependence using high-dose baclofen: A self-case report of a physician  (Case study).  Alcohol & Alcoholism 40(2):147-150, March/April 2005.

Summary: Using himself as a subject, the author, a physician with alcohol dependence and comorbid anxiety, tested whether the dose-dependent motivation-suppressing effect of baclofen in animals could be transposed to humans and suppress alcohol craving and sustain abstinence. Noting that neurologists safely prescribe up to 300 mg/day of oral baclofen to control spasticity (10 times the dosage currently used for alcohol dependence), the author self-prescribed high-dose baclofen, starting at 30 mg/day, with 20-mg increments every third day and an (optional) additional 20–40 mg/day for cravings, and found that his cravings became easier to combat. After reaching the craving-suppression dose of 270 mg/day (3.6 mg/kg) after 5 weeks, he became free of alcohol dependence symptoms and has remained  free of those symptoms effortlessly for the ninth consecutive month. His anxiety is well controlled. Somnolence disappeared with a dosage reduction to 120 mg/day, which he has now used for the eighth consecutive month. The author concludes that high-dose baclofen induced complete and prolonged suppression of symptoms and consequences of his alcohol dependence, and relieved his anxiety. He recommends that this model, integrating cure and well-being, be tested in randomized trials under medical surveillance. It offers a new concept: medication-induced, dose-dependent, complete, and prolonged suppression of substance-dependence symptoms with alleviation of comorbid anxiety. NIAAA Glossary Terms:  baclofen, drug therapy, AOD dependence, ethanol, comorbidity, anxiety, AOD craving, symptom, relapse prevention, case study, self medication, physician, dose-response relationship, human study

Murray Cochrane, Ashley Cochrane, Pramod Jauhar and Elizabeth Ashton.  Acetylcholinesterase inhibitors for the treatment of Wernicke-Korsakoff syndrome–three further cases show response to donepezil (Case study).  Alcohol & Alcoholism 40(2):151-154, March/April 2005.

Summary: The acetylcholinesterase inhibitor donepezil was used to treat three patients with Wernicke-Korsakoff syndrome for periods of 6 to 8 months. Cognitive testing [Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Mini-Mental State Examination (MMSE), Clock drawing test and six-item 2 min recall], and carer questionnaires [Informant Questionnaire (IQ Code) and Neuropsychiatric Inventory (NPI)] were performed at baseline, mid- and endpoint of the treatment period, and post-discontinuation. Partial improvement in cognitive measurements occurred progressively through the treatment period, some of which was sustained after donepezil was discontinued. Carer questionnaires also indicated improvement. Confounding factors require caution when attributing improvements to the medication, but these cases suggest that this option merits further investigation. NIAAA Glossary Terms:  treatment method, cholinesterase, enzyme inhibitors, drug therapy,  Wernicke-Korsakoff psychosis, cognitive ability, psychiatric status rating scales, questionnaire, health care worker, treatment outcome, clinical study, human study

Alcohol and Alcoholism
Volume 40, Number 1, January/February 2005
(Updated December 18, 2004)

Home Page

Giancarlo Colombo.  Preface to the Special Issue Articles on Alcohol and Cannabis.  Alcohol & Alcoholism 40(1):1, January/February 2005.

(No abstract available)

Fernando Rodríguez de Fonseca, Ignacio del Arco, Francisco Javier Bermudez-Silva, Ainhoa Bilbao, Andrea Cippitelli, and Miguel Navarro.  The Endocannabinoid System: Physiology and Pharmacology.  Alcohol & Alcoholism 40(1):2-14, January/February 2005.

Summary: The authors review the physiology and pharmacology of the endogenous cannabinoid system, a ubiquitous lipid signaling system that appeared early in evolution and has important regulatory functions throughout the body in all vertebrates. The main endocannabinoids (endogenous cannabis-like substances) are small molecules derived from arachidonic acid, anandamide (arachidonoylethanolamide), and 2-arachidonoylglycerol. They bind to a family of G-protein-coupled receptors, of which the cannabinoid CB1 receptor is densely distributed in areas of the brain related to motor control, cognition, emotional responses, motivated behavior, and homeostasis. Outside the brain, the endocannabinoid system is one of the crucial modulators of the autonomic nervous system, the immune system, and microcirculation. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and serve as retrograde signaling messengers in GABAergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters including dopamine. Endocannabinoids are transported into cells by a specific uptake system and are degraded by fatty acid amide hydrolase and monoacylglycerol lipase. Recent pharmacological advances have led to the synthesis of cannabinoid receptor agonists and antagonists, anandamide uptake blockers, and potent selective inhibitors of endocannabinoid degradation. These new tools have enabled study of the physiological roles played by the endocannabinoids and have opened up new strategies in the treatment of pain, obesity, neurological diseases including multiple sclerosis, emotional disturbances such as anxiety, and other psychiatric disorders including drug addiction. Recent advances have specifically linked the endogenous cannabinoid system to alcoholism, and cannabinoid receptor antagonism now emerges as a promising therapeutic alternative for alcohol dependence and relapse. NIAAA Glossary Terms:  cannabinoids, neurotransmitters,  neurotransmitter receptors, GABAergic neuron, dopamine, glutamate, hydrolases, lipases, synapse, sense of pain, obesity, anxiety, addiction, AOD dependence, antagonists, AODD relapse, AODU treatment method, autonomic nervous system, cognition, cell signaling, arachidonic acid, G-protein-coupled receptors, motivation, homeostasis, literature review

Balapal S. Basavarajappa and Basalingappa L. Hungund.  Role of the Endocannabinoid System in the Development of Tolerance to Alcohol.  Alcohol & Alcoholism 40(1):15-24, January/February 2005.

Summary: This review evaluates the evidence that the endocannabinoid system is involved in the development of tolerance to alcohol. The identification of a G-protein-coupled receptor, namely the cannabinoid receptor (CB1 receptor), which was activated by Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, led to the discovery of endogenous cannabinoid agonists. Until now, four fatty acid derivatives identified to be arachidonylethanolamide (AEA), 2-arachidonylglycerol (2-AG), 2-arachidonylglycerol ether (noladin ether) and virodhamine have been isolated from both nervous and peripheral tissues. Both AEA and 2-AG have been shown to mimic the pharmacological and behavioral effects of THC. The role of the endocannabinoid system in the development of tolerance to alcohol was not known until recently. Recent studies from the authors' laboratory have implicated for the first time a role for the endocannabinoid system in development of alcohol tolerance. Chronic alcohol treatment has been shown to down-regulate CB1 receptors and its signal transduction. The observed down-regulation of CB1 receptor function results from the persistent stimulation of the receptors by AEA and 2-AG, the synthesis of which has been shown to be increased by chronic alcohol treatment. The enhanced formation of endocannabinoids may subsequently influence the release of neurotransmitters. It was found that DBA/2 mice, known to avoid alcohol intake, have significantly reduced CB1 receptor function in the brain, consistent with other studies in which the CB1 receptor antagonist SR 141716A has been shown to block voluntary alcohol intake in rodents. Similarly, activation of the CB1 receptor system promoted alcohol craving, suggesting a role for the CB1 receptor gene in excessive alcohol drinking and development of alcoholism. Ongoing investigations may lead to improved understanding of the mechanisms underlying the development of alcohol tolerance and to development of therapeutic strategies to treat alcoholism. NIAAA Glossary Terms:  cannabinoids, G-protein-coupled receptors, ethanol, AOD dependence, AOD tolerance, chronic AODE, tetrahydrocannabinol, marijuana in any form, neurotransmitter receptors, psychoactive substances, signal transduction, drug therapy, literature review

Jorge Manzanares, Sergio Ortiz, José M. Oliva, Sandra Pérez-Rial, and Tomás Palomo.  Interactions Between Cannabinoid and Opioid Receptor Systems in the Mediation of Ethanol Effects.  Alcohol & Alcoholism 40(1):25-34, January/February 2005.

Summary: Recent advances in the study of the neurochemical circuits involved in the development and treatment of alcohol dependence have identified peptides and receptors as potential key targets in the treatment of problems related to alcohol consumption. The endogenous opioid system is modified by alcohol intake in areas of the brain related to reward systems, and differential basal levels of opioid gene expression are found in rodents with a high preference for ethanol. This suggests a greater vulnerability to alcohol consumption in relation to differences in genetic background. Further evidence of the involvement of opioid peptides in alcohol dependence is the ability of the opioid antagonist naltrexone to reduce alcohol intake in animal models of dependence and in alcohol-dependent patients. Abundant evidence indicates that the activation of cannabinoid receptors stimulates the release of opioid peptides, therefore the cannabinoid receptor antagonists may presumably alter opioid peptide release, thus facilitating the reduction of ethanol consumption. However, little is known about the effects of ethanol on the endogenous cannabinoid system, the vulnerability of cannabinoid receptors to alcohol intake or their neurochemical implications in reducing consumption of alcohol. This article reviews the role of opioid and cannabinoid receptor systems, their vulnerability to alcohol intake and the development of dependence, and the targeting of these systems in the treatment of alcoholism. NIAAA Glossary Terms:  neurochemistry, neuropeptides, neuropeptide receptors, brain reward pathway, endogenous opioids, gene expression, ethanol, animal selectively bred for AOD preference, naltrexone, antagonists, literature review

Iain S. Mcgregor, Kristy D. B. Dam, Paul E. Mallet, and Jason E. Gallate.  Δ⁹-THC Reinstates Beer- and Sucrose-seeking Behaviour in Abstinent Rats: Comparison with Midazolam, Food Deprivation and Predator Odour.  Alcohol & Alcoholism 40(1):35-45, January/February 2005.

Summary: Recent studies suggest that cannabinoid receptor agonists may promote relapse to drug-seeking behavior after a period of abstinence. In this study, the ability of Δ9-tetrahydrocannabinol (THC) to reinstate previously reinforced responding for alcoholic and non-alcoholic beverages was assessed in rats using a novel lick-based paradigm. Rats were initially given free access to beer (containing 4.5% ethanol v/v), near-beer (a beverage that looks and tastes like beer but contains <0.5% ethanol v/v), or isocaloric sucrose in their home cages for 3 weeks. They were then trained to lick at a tube to self-administer the pre-exposed beverage in operant chambers under a VR10 schedule in 30-minute sessions daily. After about 3 weeks of such access, the rats underwent an extinction procedure, so that licking at the tube produced no reward. Once responding had ceased, the rats were subjected to various reinstatement tests. In Experiment 1, the cannabinoid receptor agonist THC (1 mg/kg) significantly reinstated responding, previously reinforced with beer or near-beer. The effect was unlikely to be caused by increased appetite because 24-hour food deprivation had no such effect. Exposure to cat odor in the test chamber failed to reinstate responding for beer or near-beer and caused a complete inhibition of responding. In Experiment 2, THC (0.3 and 1 but not 3 mg/kg) again reinstated beer-seeking behavior while the 1 mg/kg dose also reinstated responding in sucrose trained animals. Midazolam (0.15 mg/kg but not 0.5 or 1.5 mg/kg) produced a modest reinstatement of beer-seeking but had no effect on sucrose-seeking behavior. The finding that THC can reinstate alcohol-seeking provides the impetus for further research into the involvement of the cannabinoid system in alcohol craving. However, the reinstatement of near-beer and sucrose-seeking behavior caused by THC suggests a relatively non-specific effect. This may perhaps be related to the stressor-like effects of cannabinoids, and their ability to activate key neural circuitry in the amygdala and bed nucleus of the stria terminalis. NIAAA Glossary Terms:  beer, dealcoholized beverage, sucrose, laboratory rat, reinforcement, AOD-seeking behavior, operant conditioning, tetrahydrocannabinol, midazolam, AOD craving, amygdala, brain, animal study

Gian Luigi Gessa, Salvatore Serra, Giovanni Vacca, Mauro A. M. Carai, and Giancarlo Colombo.  Suppressing Effect of the Cannabinoid Cb₁ Receptor Antagonist, Sr147778, on Alcohol Intake and Motivational Properties of Alcohol in Alcohol-preferring Sp Rats.  Alcohol & Alcoholism 40(1):46-53, January/February 2005.

Summary: The effect of the newly synthesized cannabinoid CB1 receptor antagonist SR147778 on alcohol intake and the motivational properties of alcohol was investigated in selectively bred Sardinian alcohol-preferring (sP) rats. In Experiment 1, repeated intraperitoneal (i.p.) administration of SR147778 (0.3–3 mg/kg twice daily) specifically suppressed the acquisition of alcohol drinking behavior in alcohol-naive rats exposed to the two-bottle "alcohol or water" choice regimen for 24 hours/day. In Experiment 2, an acute i.p. administration of SR147778 (2.5–10 mg/kg) specifically reduced alcohol intake in alcohol-experienced rats that were given alcohol and water under the two-bottle choice regimen in daily sessions of 4 hours. In Experiment 3, an acute i.p. administration of SR147778 (0.3–3 mg/kg) suppressed the "alcohol deprivation effect" (the extra-intake of alcohol occurring after a period of alcohol abstinence). In Experiment 4, an acute i.p. administration of SR147778 (0.3–3 mg/kg) specifically suppressed the extinction responding for alcohol, i.e. the maximal number of lever responses reached in the absence of alcohol in rats trained to lever-press for alcohol (measure of the motivational properties of alcohol). In Experiment 5, the combination of 3 mg/kg of SR147778 (i.p.) and 0.5 g/kg of alcohol (i.p.), a dose comparable with those usually consumed by sP rats in each drinking binge, failed to induce any conditioned taste aversion. These results extend to SR147778 the anti-alcohol profile of the prototype cannabinoid CB1 receptor antagonist, rimonabant (SR141716), and strengthen the hypothesis that the cannabinoid CB1 receptor is part of the neural substrate mediating alcohol intake and the motivational properties of alcohol. NIAAA Glossary Terms:  cannabinoids, tetrahydrocannabinol, neurotransmitter receptors, antagonists, ethanol, AOD consumption, AOD intake per occasion, animal selectively bred for AOD preference, laboratory rat, AOD abstinence, motivation, animal model

F. Lallemand and P. De Witte.  Ethanol Induces Higher BEC in Cb₁ Cannabinoid Receptor Knockout Mice While Decreasing Ethanol Preference.  Alcohol & Alcoholism 40(1):54-62, January/February 2005.

Summary: Previous studies using the CB1 cannabinoid receptor antagonist SR 141716 have shown that CB1 cannabinoid receptors are involved in the behavioral effects induced by chronic ethanol administration in Wistar rats. These studies have now been extended to investigate the effect of acute and chronic alcoholization on blood ethanol concentration (BEC) and ethanol preference in CB1 knockout (-/-) mice. BEC was monitored for 8 hours in both  CB1-/- male mice and CB1 male wild-type (+/+) mice, which had received an acute intraperitoneal (i.p.) injection of ethanol in 1, 3, or 5 g/kg doses. Ethanol preference was assayed in both groups of male mice in non-forced ethanol administration and forced chronic pulmonary alcohol administration for 14 and 39 days, respectively. After an acute i.p. ethanol injection of 5 g/kg, CB1-/- mice showed a significantly higher BEC during the ethanol elimination stage than the CB1+/+ mice. However, those in the 1 and 3 g/kg groups showed no significant difference. A 2–3 fold increase in BEC was observed in CB1-/- mice on days 10 and 11 after commencement of forced chronic pulmonary alcoholization in comparison with CB1+/+ mice, although comparable BEC values were assayed in both groups on day 12. In addition, these  mice showed a significantly lower preference for ethanol than CB1+/+ mice. The studies on CB1-/- and CB1+/+ mice clearly confirm the involvement of CB1 receptor on ethanol induced behavioral effects and also reveal that CB1 receptors may be implicated in ethanol absorption/distribution, particularly after administration of high ethanol doses. NIAAA Glossary Terms:  ethanol, AOD consumption, BAC, gene knockout technology, intraperitoneal administration, cannabinoids, neurotransmitter receptors, antagonists, animal study, comparative study, laboratory mice

Travis J. Worst and Kent E. Vrana.  Alcohol and Gene Expression in the Central Nervous System.  Alcohol & Alcoholism 40(1):63-75, January/February 2005.

Summary: This literature review describes recent research focusing on the analysis of gene and protein expression relevant to understanding ethanol consumption, dependence, and effects, in order to identify common themes. A selective literature search was used to collate the relevant data. Over 160 genes have been individually assessed before or after ethanol administration, as well as in genetically selected lines. Techniques for studying gene expression include Northern blots, differential display, real time reverse transcriptase polymerase chain reaction (RT-PCR), and in situ hybridization. More recently, high throughput functional genomic technology, such as DNA microarrays, has been used to examine gene expression. Recent gene expression analyses have dramatically increased the number of candidate genes (nine array papers have highlighted 600 novel gene transcripts that may contribute to alcohol abuse and alcoholism). Although functional genomic experiments (transcriptome analysis) have failed to identify a single alcoholism gene, they have illuminated important pathways and gene products that may contribute to the risk of alcohol abuse and alcoholism. NIAAA Glossary Terms:  gene expression, central nervous system, ethanol, AOD consumption, AOD abuse, AOD dependence, acute AODE, chronic AODE, genetic technology, Northern blotting, reverse transcriptase polymerase chain reaction, gene transcription, genome, DNA, risk factors, literature review

Dai-Jin Kim, Su-Jung Yoon, Bomoon Choi, Tae-Suk Kim, Young Sup Woo, Won Kim, Hugh Myrick, Bradley S. Peterson, Young Bin Choi, Yong-Ku Kim, and Jaeseung Jeong.  Increased Fasting Plasma Ghrelin Levels During Alcohol Abstinence.  Alcohol & Alcoholism 40(1):76-79, January/February 2005.

Summary: The peptide hormone ghrelin antagonizes the action of leptin and is thereby thought to regulate feeding behavior. The actions of ghrelin and leptin appear to be mediated by the neuropeptide Y (NPY) and Agouti-related protein (AGRP) system. Recent studies have suggested that leptin and NPY play significant roles in the pathophysiology of alcoholism. The present study sought to determine whether ghrelin is associated with the state and duration of abstinence in alcoholics. Fasting plasma ghrelin levels were compared between alcoholics (n = 47) during a period of abstinence and control subjects (n = 50). Fasting plasma ghrelin levels were higher in abstinent alcoholics than in controls, there was a positive correlation between ghrelin levels and the duration of abstinence, and daily alcohol intake prior to abstinence was inversely related to ghrelin levels. These findings suggest that ghrelin plays a role in the pathogenesis of alcohol dependence, particularly during the abstinence period, in individuals with chronic alcoholism. NIAAA Glossary Terms:  peptides, hormones, leptin, antagonists, neuropeptide Y, pathogenesis, AOD dependence, AOD abstinence, AOD intake per occasion, controlled study, correlation analysis, human study

K. Junghanns, U. Tietz, L. Dibbelt, M. Kuether, R. Jurth, D. Ehrenthal, S. Blank, and J. Backhaus.  Attenuated Salivary Cortisol Secretion under Cue Exposure Is Associated with Early Relapse.  Alcohol & Alcoholism 40(1):80-85, January/February 2005.

Summary: The aim was to determine if the risk of relapse in alcohol dependence is predicted by the subjective experience of cue exposure (CE) and/or cortisol reactivity to alcohol cues. Salivary cortisol and self-ratings of "tension" and "desire to drink" were measured in detoxified alcohol-dependent inpatients (N = 32) during CE sessions conducted in the first and third week of motivation enhancement therapy. Subjects completed the Toronto Alexithymia Scale (TAS-20) and the Abbreviated Alcohol Expectancy Questionnaire (B-AEQ) towards the end of the inpatient treatment to measure emotional self-awareness and the expected positive effects of alcohol. Six weeks after the end of the inpatient treatment, 15 patients were abstinent. Relapse was verified or was presumed for 17 patients. Those who had relapsed had shown an attenuated response to CE in the third week as an inpatient but did not differ from abstainers in subjective reaction to cues. Subjective ratings of CE were not related to salivary cortisol or relapse but showed several associations with factors one and two of the TAS-20. The expectancy of enhanced social contacts by using alcohol (factor 1 of the B-AEQ) correlated negatively with the decline in salivary cortisol during the CE session in the third week of treatment. Subjective ratings of CE correlated with Alexithymia scores. In conclusion, alcoholics who use alcohol to enhance their social contacts typically lack hypothalamo-hypophyscal-pituitary-adrenocortical (HPA) reactivity in the early period of abstention. They are at an increased risk of early relapse and perhaps use alcohol to increase cortisol secretion again. NIAAA Glossary Terms:  AOD dependence, AOD abstention, cue reactivity, cortisol, saliva analysis, hypothalamic-pituitary-adrenal axis, expectancy, correlation analysis, sociability, social behavior, alexithymia, human study

Jun-Ichi Iga, Takahide Taniguchi, and Tetsuro Ohmori.  Acute Abdominal Distension Secondary to Urinary Retention in a Patient after Alcohol Withdrawal.  Alcohol & Alcoholism 40(1):86-87, January/February 2005.

Summary: The authors report a case of symptomatic abdominal distension due to urinary retention after alcohol withdrawal. The timing of the onset suggests that it was induced by alcohol withdrawal. Several cases of alcohol-induced bladder dysfunction have been reported previously, but the mechanism of its development is varied and unclear. NIAAA Glossary Terms:  case study, bladder function, urinary system disorder, urination, abdomen, AOD withdrawal syndrome, AOD dependence, human study

Sally Casswell.  Alcohol Brands in Young Peoples' Everyday Lives: New Developments in Marketing (Commentary).  Alcohol and Alcoholism 39(6):471-476, November/December 2004.

Summary: The author discusses the response of young people to new developments in alcohol marketing, what this marketing does for the alcohol industry, and the need for new policy responses.  The new developments are likely to be important for young people because of their use of new technology and the role of brands in their lives. NIAAA Glossary Terms: adolescent, young adult, marketing strategy, alcoholic beverage industry, public policy on AOD, targeted advertising, commentary

Jim Slattery.  Pragmatic Trials and the ARES Study (Commentary).  Alcohol and Alcoholism 39(6):477, November/December 2004.

(No abstract available)

A. M. Brind, A. Hurlstone, D. Edrisinghe, I. Gilmore, N. Fisher, M. Pirmohamed, and A. A. Fryer. The Role of Polymorphisms of Glutathione S-transferases Gstm1, M3, P1, T1 and A1 in Susceptibility to Alcoholic Liver Disease.  Alcohol and Alcoholism 39(6):478-483, November/December 2004.

Summary: It has been proposed that oxidative stress is an important factor in the pathogenesis of alcohol-related liver damage. Because there is evidence for genetic susceptibility to alcohol-related liver disease, the authors of this study compared the frequency of polymorphisms of glutathione S-transferases (GSTs), a group of enzymes that protect against oxidant stress. GSTM1, GSTM3, GSTP1, GSTT1, and GSTA1 were analyzed by polymerase chain reaction (PCR) on leucocyte DNA in patients with alcohol-related chronic liver disease, heavy drinkers, and normal controls. Genotype frequences of GSTM1, GSTM3, or GSTP1 did not differ significantly among patients, drinking, and non-drinking controls from the three centers partcipating in the study. There was a significant increase in the GSTT1 null alcoholic liver disease (ALD) patients in Liverpool (UK) compared with corresponding non-drinking controls (26.3 and 14.6% respectively; p = 0.044, odds ratio (OR) = 2.1; 95% confidence interval [CI], 1.1–4.7), but this was not observed in the Birmingham and North Staffordshire cohorts. For GSTA1, the –69 CC genotype was associated with increased risk of ALD in the Liverpool group, but with a reduced risk in the North Staffordshire group. This case-control study was unable to demonstrate a reproducible significant association of GST polymorphisms with susceptibility to ALD, but further study of GSTA1 and GSTT1 may be warranted. NIAAA Glossary Terms:  alcoholic liver disorder, heavy AOD use, AOD nonuse, chronic AODE, genetic theory of AODU, genetic polymorphism, gene frequency, genotype, genetic correlation analysis, polymerase chain reaction, DNA, leukocytes, transferases, glutathione, isoenzymes, risk analysis, case-control study, human study

Pascal Perney, Pierre Portalès, Jacques Clot, François Blanc, and Pierre Corbeau.  Diminished CD4+ T Cell Surface CCR5 Expression in Alcoholic Patients.  Alcohol and Alcoholism 39(6):484-485, November/December 2004.

Summary: The C-C chemokine receptors, particularly the CCR5, appeared to play an important role in T cell-mediated inflammatory reactions. This study was assessed the impact of chronic alcohol consumption on CCR5 expression in vivo. Alcoholic men (n = 14) hospitalized for detoxification were compared with age-matched controls (n = 49). The CD4+ T cell surface CCR5 densities were drastically lower in alcoholics, averaging 5,319 molecules/cell (95% confidence interval [CI], 4477–6162], compared to the controls, 10,944 molecules/cell (95% CI, 9,929-11,959; p < 10-4). It was concluded that chronic alcohol consumption is associated with significantly decreased CCR5 expression, which could favor Th1/Th2 imbalance. NIAAA Glossary Terms:  cytokines, chronic AODE, AOD dependence, receptors, T lymphocyte, in vivo study, case-control study, detoxification, hospital, human study

Frédéric Lallemand, Philippe Soubrié, and Philippe De Witte.  Effects of CB1 Cannabinoid Receptor Blockade on Ethanol Preference after Chronic Alcohol Administration Combined with Repeated Re-exposures and Withdrawals.  Alcohol and Alcoholism 39(6):486-492, November/December 2004.

Summary: SR141716A is a cannabinoid CB1 brain receptor antagonist that differentially affects the ethanol preference of chronically alcoholized rats when administered during cycles of ethanol exposure and withdrawal. This study investigated ethanol preference in chronically alcoholized rats that underwent regular withdrawal periods during which SR141716A was administered. SR141716A at two different doses was administered intraperitoneally to Wistar rats at the end of a 4-week period of chronic alcoholization, as they began a 10-day cycle of alcohol withdrawal. The withdrawal period was followed by another 10-day period of chronic ethanol exposure. A second set of experiments included an additional cycle of ethanol withdrawal and re-exposure. Preference for ethanol versus water started at the end of the first or second chronic ethanol re-exposure for a period of at least 30 days. In rats pretreated with the higher dose of SR141716A (10 mg/kg/day), ethanol preference during free choice was significantly increased after two ethanol re-exposures. In contrast, pretreatment with the lower SR141716A dose (3 mg/kg/day) induced no significant change in ethanol intake during the free choice followed by either one or two ethanol re-exposures. Thus SR141716A at a 10 mg/kg/day dose significantly increased ethanol preference which was dependent on both the number of ethanol withdrawals and chronic ethanol re-exposures, while 3 mg/kg/day had no significant effect on ethanol preference. NIAAA Glossary Terms:  cannabinoids, antagonists, receptors, brain, ethanol, AOD preference, chronic AODE, AOD withdrawal syndrome, AOD intake per occasion, animal study, laboratory rat

Stefan Bleich, Kristina Bayerlein, Udo Reulbach, Thomas Hillemacher, Dominikus Bönsch, Birgit Mugele, Johannes Kornhuber, and Wolfgang Sperling.  Homocysteine Levels in Patients Classified According to Lesch's Typology.  Alcohol and Alcoholism 39(6):493-498, November/December 2004.

Summary: Because it has been suggested that elevated total plasma homocysteine levels might preduct alcohol withdrawal seizures, total plasma homocysteine levels were investigated in actively drinking alcoholic patients who were classified according to Lesch's typology. Total plasma homocysteine levels were determined in 144 non-abstinent chronic alcoholics (115 men, 29 women; aged 22-67 years). The patients were classified according to Lesch's typology (LT) and were divided into two groups: LT 1 (n = 27) and LT 2 to 4 (n = 117). Patients with or without a history of alcohol withdrawal seizures were differentiated within these groups. All patients with a history of alcohol withdrawal seizures had significantly elevated plasma homocysteine concentrations at admission compared with those without seizures (Mann-Whitney U, p < 0.001). Furthermore, patients classified as LT 1 who suffered from an alcohol withdrawal seizure (n = 12) had significantly higher plasma homocysteine levels (Z = –2.31, p = 0.02) compared to the corresponding types 2 to 4 (n = 24). A logistic regression analysis revealed that withdrawal seizures were best predicted by a high homocysteine level at admission; this was even more pronounced in LT 1 (Wald's chi-squared  = 10.7; odds ratio [OR] = 1.24; 95% confidence interval [CI], 1.03-1.51; p < 0.001) when compared with LT 2 to 4 (chi-squared = 10.6; OR = 1.06; 95%CI, 1.03-1.14; p = 0.004). The authors believe this is the first study to evaluate homocysteine levels in patients who were classified according to Lesch's typology. They conclude that homocysteine levels on admission may be a useful screening method to identify actively drinking patients at risk of alcohol withdrawal seizures, especially in Lesch type 1 alcoholics. NIAAA Glossary Terms:  [homocysteine], [Lesch's typology], AOD dependence, AOD withdrawal syndrome, AODR seizure, predictive factor, risk factors, alcohol use disorder classification, plasma, regression analysis, statistical estimation, medical screening and diagnostic method, clinical study, human study

Bykov, M. Palmén, L. Piirainen, and K. O. Lindros.  Oral Chronic Ethanol Administration to Rodents by Agar Gel Diet.  Alcohol and Alcoholism 39(6):499-502, November/December 2004.

Summary: This article describes a new method for chronic ethanol administration to rodents as an alternative to current procedures, which are labor intensive and require specially designed equipment. A commercial liquid diet preparation was made into a gel by addition of 0.5% agar. The gel, containing 5.3% ethanol, was offered in Falcon tubes equipped with a feeding opening. Ingestion of the gel by C57/Bl mice resulted in high blood ethanol levels (average 43 mM), and marked liver steatosis and significantly increased serum alanine aminotransferase levels developed after 6 weeks. Administration of ethanol in a nutritionally adequate gel provides a simple method for studies on chronic ethanol effects in rodents. NIAAA Glossary Terms:  ethanol, AOD consumption, chronic AODE, diet, nutritional value or requirement, alcoholic liver disorder, fatty liver, alanine aminotransferase, animal study, laboratory mice, laboratory study

Nathaniel C. O. Khaole, Vijay A. Ramchandani, Denis L. Viljoen, and Ting-kai Li.  A Pilot Study of Alcohol Exposure and Pharmacokinetics in Women with or Without Children with Fetal Alcohol Syndrome.  Alcohol and Alcoholism 39(6):503-508, November/December 2004.

Summary: Alcohol exposure and alcohol pharmacokinetics were compared in women (n = 10) who had given birth to children with fetal alcohol syndrome (FAS) and women who had not given birth to FAS children (n = 20). The FAS mothers and the controls were studied to determine how they metabolize alcohol in a single limited-access quasi-experimental session of voluntary alcohol consumption in which they had free choice to consume any amount of their favorite beverage for about 2.5 hours, but their drinking was terminated if their breath alcohol concentration (BrAC) exceeded 150 mg%. BrAC was measured during ethanol consumption and for several hours afterward, for estimation of alcohol exposure and pharmacokinetics. FAS mothers consumed significantly more alcohol and achieved significantly higher peak BrAC levels than controls. The rate of decline of alcohol from the circulation varied twofold across subjects but did not differ significantly between the two groups. This study found no difference in alcohol pharmacokinetics in free-choice drinking by non-pregnant women who either have given or have never given birth to FAS children. However, mothers of FAS children tended to consume more alcohol per session. The authors recommend further studies in larger samples to confirm these findings and to examine drinking patterns and other factors that may increase the risk of FAS in children of women who drink alcohol during pregnancy. NIAAA Glossary Terms:  fetal alcohol syndrome, mother, alcoholic beverage, AOD consumption, AOD intake per occasion, ethanol metabolism, pharmacokinetics, breath alcohol analysis, controlled study, human study

Adele Mckinney and Kieran Coyle.  Next Day Effects of a Normal Night's Drinking on Memory and Psychomotor Performance.  Alcohol and Alcoholism 39(6):509-513, November/December 2004.

Summary: The effects of a "normal" evening of alcohol drinking on cognitive performance was investigated in social drinkers (N = 48; 33 women, 15 men; 18-43 years of age). Participants were required to consume their usual quantity of any type of alcoholic beverage in their chosen company (hangover situation), but the timing of drinking was restricted to the period between 22:00 and 02:00 hours on the night before testing. Testing included memory and psychomotor performance tests. Testing was also performed after an evening of abstinence (no-hangover situation), following a counterbalanced design using repeated measures, with time of testing (09:00, 11:00, and 13:00 hours) and order of testing (hangover/no hangover; no hangover/hangover) as "between-participant" factors in the analysis. Test sessions were conducted a week apart. The morning after alcohol (mean consumption: 14.7 units for men; 10.4 units for women), free recall was impaired at 09:00 hours and delayed recognition and psychomotor performance were impaired throughout the morning, despite blood alcohol levels of zero or very nearly zero. It was concluded that memory and psychomotor performance are impaired on the morning after heavy social drinking. NIAAA Glossary Terms:  cognitive and memory disorder, psychomotor impairment, social AOD use, alcoholic beverage, hangover (any AOD substance), AOD abstinence, BAC, gender differences, human study

Claudia I. Rupp, W. Wolfgang Fleischhacker, Armand Hausmann, Dolores Mair, Hartmann Hinterhuber, and Martin Kurz.  Olfactory Functioning in Patients with Alcohol Dependence: Impairments in Odor Judgements.  Alcohol and Alcoholism 39(6):514-519, November/December 2004.

Summary: Olfactory judgements were assessed in nonamnesic and nondemented patients with alcohol dependence. Alcohol-dependent patients (n = 30) and healthy control subjects (n = 30), well matched for gender, age and smoking status, and screened for olfactory sensitivity, were asked to rate intensity, familiarity, edibility and pleasantness of 16 odors using visual rating scales. Compared with controls, alcohol-dependent patients showed lower scores in odor familiarity and impaired edibility judgments. These impairments were bilateral; independent of age, gender, general mental abilities, and length of abstinence; and not attributable to smoking or impaired olfactory sensitivity. No differences were evident between groups in odor intensity and pleasantness judgments. The results extend prior findings of alcohol-related olfactory deficits, indicating impairments in olfactory processes of odor familiarity and edibility in alcohol-dependent patients. Although the basis of these deficits is still unknown, the finding of a distinct pattern of olfactory function, with spacing of perception of pleasantness and familiarity, suggests that there is no generalized olfactory impairment but that neural olfactory networks may be affected differently. NIAAA Glossary Terms:  smell, olfactory perception, olfactory system disorder, AOD dependence, controlled study, human study

Paul Kiritzé-Topor, Dominique Huas, Claude Rosenzweig, Sylvie Comte, François Paille, and Philippe Lehert.  A Pragmatic Trial of Acamprosate in the Treatment of Alcohol Dependence in Primary Care.  Alcohol and Alcoholism 39(6):520-527, November/December 2004.

Summary: The effectiveness of pharmacotherapy with acamprosate (calcium acetylhomotaurinate) was assessed in alcohol-dependent patients treated in a naturalistic primary care setting in France. The ARES (Acamprosate et Répercussions Économiques et Sociales; Acamprosate and Economic and Social Repercussions) study was performed by 149 general practitioners treating patients fulfilling standard diagnostic criteria (DSM-IV) for alcohol dependence. Exclusion criteria included contraindications to acamprosate, co-medication with naltrexone, and multiple substance abuse. Eligible patients were randomized either to standard care alone or standard care with acamprosate, using an open-label design and followed up quarterly for a period of 1 year. The primary outcome variable was the change from baseline on the Alcohol-Related Problems Questionnaire (ARPQ). Secondary efficacy variables were abstinence, Clinical Global Impression, quality of life measured with the SF-36, and incidence of adverse events. A total of 422 patients were included, 348 (82%) of whom completed the protocol as planned. At the end of the study, patients in the acamprosate group had significantly better outcomes in terms of total ARPQ score, change from baseline (-2.61 vs -3.44), and number of subjects with no alcohol-related problem. On average, patients treated with acamprosate had one less alcohol-related problem than the controls. The number needed to treat in order to save one additional patient from alcohol-related problems compared to standard care was 7.14. Statistically significant differences in favor of the acamprosate group were observed for all secondary efficacy outcome measures including quality of life. NIAAA Glossary Terms:  AOD dependence, AOD abstinence, drug therapy, calcium acetylhomotaurinate, primary care, general practitioner, randomized controlled trial, follow-up study, treatment follow-up, treatment outcome, AODR disorder, diagnostic criteria, quality of life, adverse drug effect, clinical study, human study

Alan De Sousa and Avinash De Sousa.  A One-year Pragmatic Trial of Naltrexone vs Disulfiram in the Treatment of Alcohol Dependence.  Alcohol and Alcoholism 39(6):528-531, November/December 2004.

Summary: The efficacy of naltrexone and disulfiram in preventing an alcoholic relapse in routine clinical practice were compared. Alcohol-dependent men (N = 100) were randomly allocated to a year of treatment with either naltrexone or disulfiram. Patients, their accompanying family member, and the treating psychiatrist were aware of the nature of treatment given. Alcohol consumption, craving, and adverse events were recorded by the treating psychiatrist weekly for the first three months, then every two weeks for the rest of the year. Serum gamma-glutamyl transferase (GGT) was measured at the start and the end of the study. At the end of the year, 97 patients were still in contact. Relapse, the consumption of >5 drinks (40 g of ethanol) in a 24-hour period, occurred at a mean of 119 days with disulfiram and at 63 days with naltrexone (p = 0.020). Mean serum GGT, which had not differed between the two groups initially, was 117 U/l with naltrexone and 85 U/l with disulfiram (p = 0.038) at the end of the study. Abstinence throughout the study was maintained by 86 percent of the patients with disulfiram compared to 44% with naltrexone (p = 0.0009), but patients allocated to naltrexone had significantly less craving. It was concluded that disulfiram is superior to naltrexone in preventing a relapse among alcohol-dependent men with family support. The authors recommend comparison between these treatments in other settings and in different types of alcoholics. NIAAA Glossary Terms:  AOD dependence, AOD craving, AOD abstinence, AODD relapse, relapse prevention, alcohol relapse prevention agents, disulfiram, naltrexone, drug therapy, gamma glutamyl transferase, family support, clinical trial, comparative study, human study

Mauri Aalto and Kaija Seppä.  Usefulness, Length and Content of Alcohol-related Discussions in Primary Health Care: The Exit Poll Survey.  Alcohol and Alcoholism 39(6):532-535, November/December 2004.

Summary: Patients' opinions of the usefulness of alcohol-related discussions with general practitioners (GPs), the time used for the discussion, and the discussion's main content were evaluated based on an exit poll survey of 2,000 consecutive patients immediately after GP consultations. The response rate was 60.2% (N = 1,203). Of the patients 11.6% (n = 139) reported that they were asked or advised about alcohol during the consultation. The time used for discussion about alcohol for most patients was less than 4 minutes, longer for heavy drinkers than for non-heavy drinkers. The main topics of the discussion dealt with quantities consumed and harm caused by alcohol. The majority of the patients (81%) reported that discussions concerning alcohol were useful; heavy drinkers and non-heavy drinkers did not differ in this assessment. In summary, discussions about alcohol in primary health care were rare and short, but patients' opinions about their usefulness were mainly positive. NIAAA Glossary Terms:  general practitioner, primary health care, alcoholic beverage, AOD use pattern, brief intervention, survey, harm reduction, human study

T. Alwyn, B. John, R. J. Hodgson, and C. J. Phillips.  The Addition of a Psychological Intervention to a Home Detoxification Programme.  Alcohol and Alcoholism 39(6):536-541, November/December 2004.

Summary: The aim was to determine whether a relatively brief psychological intervention adds to the effectiveness of home detoxification. Participants (N = 91) were randomly assigned to either the psychological intervention or treatment as usual. Community psychiatric nurses were trained to administer the brief psychological intervention involving motivational interviewing, coping skills training, and social support. A manual was developed in order to standardize the training and implementation. At the 3-month and 12-month follow-ups, the psychological intervention resulted in significant positive changes in alcohol consumption, abstinent days, social satisfaction, self-esteem, and alcohol-related problems. A cost analysis revealed that the cost of the psychological intervention was one-ninth that of inpatient treatment. It was concluded that adding a psychological intervention to a home detoxification program was successful and cost-effective. NIAAA Glossary Terms:  AOD dependence, AOD consumption, AOD abstinence, AOD effects and AODR problems, home health care, detoxification, psychological counseling, coping skills, social support, nurse, follow-up study, patient satisfaction, self-esteem, cost-effectiveness of AOD health services, evaluation study, human study

Falk Kiefer and Klaus Wiedemann.  Combined Therapy: What Does Acamprosate and Naltrexone Combination Tell Us?  Alcohol and Alcoholism 39(6):542-547, November/December 2004.

Summary: Both acamprosate (calcium acetylhomotaurinate) and naltrexone have been shown to be efficacious for relapse prevention in the treatment of alcoholism, but there is limited evidence as to whether combined treatment with these drugs is efficacious and safe. The authors of this article reviewed the three pre-clinical and four clinical studies that have been published to date on either the combined tolerability or efficacy of these agents. The available data show no occurrence of severe adverse events during combined treatment. The most significant side-effects reported are diarrhea and nausea. Pre-clinical studies of the efficacy of combined treatment are not yet conclusive, but clinical data show the superiority of combined treatment compared with both placebo and acamprosate monotherapy. The synergistic effect of combined treatment remained after 12 weeks of drug-free follow-up. The combination of acamprosate with naltrexone in a clinical sample seems to be efficacious and safe. Numerous alcohol dependent patients could benefit from the combination, particularly those who respond insufficiently on monotherapeutic treatment with either acamprosate or naltrexone. NIAAA Glossary Terms:  drug therapy, relapse prevention, AOD dependence, AODD relapse, naltrexone, calcium acetylhomotaurinate, combination drug therapy, beneficial vs adverse drug effect, synergistic drug interaction, literature review, animal study, human study, clinical trial

Odd Nilssen.  Long-term Effect of Brief Intervention in At-risk Alcohol Drinkers: A 9-year Follow-up Study.  Alcohol and Alcoholism 39(6):548-551, November/December 2004.

Summary: The long-term effect of brief intervention with people who consume alcohol at levels considered risky were assessed in a 9-year follow-up study. The participants were 338 men and women attending a general population screening study in 1986 who were identified as at-risk drinkers. They were randomly assigned to one of three groups, two of which received slightly different brief interventions and the third group serving as controls. After 1 year alcohol intake was 50% lower in the intervention groups and 20% higher in the control group. The controls were then advised to reduce their drinking. This article reports outcomes in 247 subjects (73.1%) from the 1986 study who were re-assessed 9 years after these interventions. Serum gamma-glutamyl transferase (GGT) was examined and compared with values in 1986. A "pseudo-control" group was established to compare "treated" and "untreated" subjects. After 9 years, the mean GGT levels in the original study groups were significantly reduced. The reductions achieved in the three original groups did not significantly differ from each other, but they were significantly greater than in the "pseudo-control" group. Brief intervention therefore appears to have a longlasting impact. At 9 years follow-up, the at-risk drinkers displayed GGT values close to that of the background population. NIAAA Glossary Terms:  follow-up study, AOD user, problematic AOD use, amount of AOD use, high-risk group, brief intervention, gamma glutamyl transferase, controlled study, comparative study, evaluation, health risk assessment , human study

Cheryl J. Cherpitel, Yu Ye, and Jason Bond.  Alcohol and Injury: Multi-level Analysis from the Emergency Room Collaborative Alcohol Analysis Project (ERCAAP).  Alcohol and Alcoholism 39(6):552-558, November/December 2004.

Summary: The relationship between individual-level characteristics and site-level contextual variables on the association of acute alcohol use and injury was analyzed. Blood alcohol concentrations (BAC) and survey data were collected at the time of emergency department (ED) visits, between 1985 and 2003 on probability samples of injured and non-injured patients (n = 18,438) from 31 EDs in seven countries (Argentina, Canada, Italy, Mexico, Poland, Spain, USA). Data analysis with hierarchical linear modeling with control for gender and age revealed that  BAC and self-reported alcohol consumption were predictive of an injury (compared to a non-injury), with odds ratios of 1.51 and 1.58 respectively. The likelihood of injury given a positive BAC and self-report was less for heavier drinkers (those reporting five or more drinks on an occasion) than for lighter drinkers, and was greater in societies with greater detrimental drinking patterns than those with lower detrimental patterns. The results suggest a moderate but robust association of a positive BAC and self-report with admission to the ED for an injury, which is modified by the patient's usual heavier drinking and by societal drinking patterns. NIAAA Glossary Terms:  emergency care, injury, AOD consumption, heavy AOD use, light AOD use pattern, BAC, self-report, predictive factor, risk factors, risk analysis, relative risk, statistical modeling, international differences, cultural patterns of drinking, human study

---

D. Colin Drummond.  An alcohol strategy for England: The good, the bad and the ugly.  Alcohol & Alcoholism 39(5):377-379, 2004.

(No abstract available.)

Salim Mottagui-Tabar, Shane McCarthy, Jana Reinemund, Björn Andersson, Claes Wahlestedt, and Markus Heilig.  Analysis of 5-hydroxytryptamine 2C receptor gene promoter variants as alcohol-dependence risk factors.  Alcohol & Alcoholism 39(5):380-385, September/October 2004.

Summary: The objective was to determine whether polymorphic variants of the 5-hydroxytryptamine 2C (HTR2C) receptor gene promoter are associated with alcohol dependence. Allele frequencies of five HTR2C promoter polymorphisms were compared in a Nordic population of alcohol dependent individuals (males: n = 309; females: n = 127) and ethnically matched controls (males: n = 83; females: n = 190) in whom any diagnosis of substance disorder was excluded. Alcohol dependent subjects were subtyped into Type I (late onset) and Type II (early onset) alcoholics. None of the individual polymorphisms were significantly associated with alcohol dependence. A common promoter haplotype (GAGG) exhibited different distribution frequencies between males and females (Type I), but this association became non-significant when Bonferroni's multiple-testing correction was applied. Although no association was found between alcohol dependence and five common promoter polymorphisms, and the constituted haplotypes, the analysis tends to indicate gender and sub-type differences. The authors suggest a follow-up study using larger samples to improve the power to detect the genetic influences of HTR2C in alcohol dependence. NIAAA Glossary Terms:  genetic polymorphism, risk factors, AOD dependence, receptors, allele, gene frequency, Scandinavia, early AODU onset, late AODU onset, Cloninger's typology, haplotype, gender differences, genetic correlation analysis, human study

Johannes Frank, Karin Witte, Wieland Schrödl, and Christine Schütt.  Chronic alcoholism causes deleterious conditioning of innate immunity.  Alcohol & Alcoholism 39(5):386-392, September/October 2004.

Summary: The immune consequences of chronic alcoholism were examined in relation to the known association between alcoholism and greater incidence and severity of infections. In 36 alcoholics without liver disease the following measures of immune competence were measured at the commencement of withdrawal from alcohol: the immunophenotypes of cells, acute phase proteins, the endotoxin-neutralizing capacity (ENC) of the serum, titers of anti-lipopolysaccharide (LPS) antibodies, and ex vivo cytokine inducibility in T cells and monocytes. The cytokines examined were tumor necrosis factor-alpha (TNF-α), interleukin (IL)1β, IL1RA, IL4, IL6, IL8, IL10, and IL12. The results were compared to those from healthy volunteers. Measures were repeated after 8-13 days of abstinence. LPS-binding protein (LBP) and soluble CD14 (sCD14) were significantly increased in patients' sera at the outset of withdrawal, whereas reduced titers of anti-LPS immunoglobulin G (p = 0.012) and a reduced ENC (p = 0.001) were measured. Only ENC rapidly returned to normal values after withdrawal therapy. Cytokine induction with phorbol ester showed no significant alterations in patients' T cells. Patients' monocytes, however, responded to LPS stimulation with significantly enhanced production of IL1β, but significantly reduced production of TNF-α and IL12. While IL1 and TNF-α responses normalized after withdrawal, impaired IL12 response persisted throughout the observation period of 2 weeks. It was concluded that alcoholism causes a prolonged LPS-mediated hypoinflammatory conditioning of the innate (but not the adaptive) immune system that is not reversed immediately after withdrawal and predisposes to infections and sepsis by blunting initial response to pathogens. NIAAA Glossary Terms:  AOD dependence, AOD abstinence, immune system, immune response, infection, alcoholic liver disorder, antibodies, tumor necrosis factor-alpha, T lymphocyte,  interleukin, lipopolysaccharide, pathogenesis, human study

María Dolores Mayas, María Jesús Ramírez-Expósito, María Jesús García, Pilar Carrera, and José Manuel Martínez-Martos.  Ethanol modulates neuropeptide-degrading aminopeptidases at synapse level in calcium-dependent conditions.  Alcohol & Alcoholism 39(5):393-405, September/October 2004.

Summary: The effects of ethanol on alanyl-, arginyl-, cystyl-, leucyl- and tyrosyl-aminopeptidase activities were studied under basal and K+-stimulated conditions at the synapse level, using mouse frontal cortex synaptosomes and their incubation supernatant in a Ca2+-containing or Ca2+-free medium . Under basal conditions, synaptosome aminopeptidase activities showed an inhibitory or biphasic response depending on the concentration of ethanol and the aminopeptidase assayed. Supernatant activities showed a more complex response. Under K+-stimulated conditions, ethanol inhibited all synaptosome aminopeptidases assayed in presence of Ca2+. However, different responses were obtained in the absence of Ca2+ depending on the concentration of ethanol used. In the supernatant, the highest concentration of ethanol inhibited the K+-stimulated increase on aminopeptidase activities, although the lowest concentration enhanced the release in presence of Ca2+. In absence of Ca2+, ethanol blocked the K+-stimulated decrease or increased the activity depending on the concentration of ethanol. The changes on aminopeptidase activities induced by ethanol may reflect the functional status of their corresponding endogenous substrates. Ethanol may influence opioid peptides, oxytocin, vasopressin, and the brain renin-angiotensin system through their degrading enzymes. NIAAA Glossary Terms:  ethanol, synaptosome, peptides, enzymes, amino acids, alanine, arginine, cystine, leucine, tyrosine, potassium, calcium, opioids, oxytocin, vasopressin, renin, angiotensin, enzymes, animal study, laboratory mice

Hiroshi Kinoshita, Michael S. Harbuz, Minori Nishiguchi, Harumi Ouchi, Takako Minami, Takao Utsumi, Hiroyuki Motomura, and Shigeru Hishida.  High alcohol preferring (HAP) and low alcohol preferring (LAP) rats show altered proopiomelanocortin (POMC) messenger RNA expression in the arcuate nucleus.  Alcohol & Alcoholism 39(5):406-409, September/October 2004.

Summary: Proopiomelanocortin (POMC) and neuropeptide Y gene expression in the arcuate nucleus of the hypothalamus were compared in high alcohol preference (HAP) rats and low alcohol preference (LAP) rats under basal conditions using in situ hybridization histochemistry. Expression of POMC mRNA was was significantly higher in HAP rats than in LAP rats, but the two rat lines did not differ in neuropeptide Y mRNA expression. The results suggest that an endogenous opioid system may contribute to alcohol preference in these rat lines.

Justin Grobe, Neil Rowland, and Michael Katovich.  Role of angiotensin II and the subfornical organ in the pharmacological actions of ethanol.  Alcohol & Alcoholism 39(5): 410-417, September/October 2004.

Summary: This study investigated whether angiotensin II mediates the hypothermic effects of ethanol and whether the effects of angiotensin are mediated centrally. It was also hypothesized that the subfornical organ (SFO) is a site responsible for the alterations in body temperature and aerial righting reflex mediated by ethanol and for the modulation of ethanol consumption in rats. Experiments were conducted to evaluate the role of both peripheral and central administration of losartan, a selective angiotensin type 1 receptor antagonist, on ethanol-induced hypothermia. Subsequent studies were undertaken in SFO-lesioned rats to evaluate the effects of SFO-lesion on alcohol intake, the thermal response to alcohol and angiotensin, and the aerial righting reflex. Selective antagonism of the angiotensin II type 1 receptor, administered either peripherally or centrally, attenuated not only the fall in colonic temperature but also attenuated the transient rise in tail skin temperature that was associated with ethanol administration. The thermal responses to both angiotensin and ethanol were similarly attenuated in SFO-lesioned rats. Likewise the aerial righting reflex, which has previously been shown to be impaired by losartan treatment, was also significantly attenuated in SFO-lesioned animals. Alcohol intake, as determined by a 48-hour, two-bottle preference test also revealed that SFO-lesioned animals consumed significantly less alcohol (ethanolic beer) than did controls. It was concluded that ethanol-induced temperature responses are mediated by the renin-angiotensin system and that this interaction is mediated centrally. The results also demonstrate that the SFO is a site that mediates several neurobiological effects of ethanol, possibly via the renin-angiotensin system.

Ken D. Sumida, Tauseef Qureshi, Michael J. Catanzaro, Steven M. Arimoto, and Janeen M. Hill.  Chronic alcohol consumption yields sex differences in whole-body glucose production in rats.  Alcohol & Alcoholism 39(5):418-426, September/October 2004.

Summary: The effects of chronic alcohol consumption (8 weeks) on glucose kinetics, in the absence and presence of an acute ethanol dose (4 g/kg), were examined in fasted (48 hours) male and female Wistar rats. Primed continuous infusions of tritium- and carbon 14-labeled glucose were used to assess rates of glucose appearance (Ra), glucose disappearance (R d), and apparent glucose carbon recycling. After injecting the male and female controls with water (4 g/kg), there were no significant alterations in glucose kinetics. Compared to controls, chronic alcohol-fed female animals (injected with water) demonstratedsignificantly lower glucose Ra, blood glucose concentration, and apparent glucose carbon recycling for most of the experimental period. In separate groups injected with ethanol, the glucose Ra fell by 31% for male rats fed the control diet (MC), 43% for male rats fed the ethanol diet (ME), 29% for female rats fed the control diet (FC), and 42% for female rats fed the ethanol diet (FE). Compared to controls (MC and FC), the blood glucose concentration was significantly lower before and after the ethanol injection for FE. In addition, FE animals had significantly lower rates of glucose Ra and glucose carbon recycling compared to controls before and after the ethanol injection. ME animals demonstrated similar declines in glucose Ra (compared to FE), but only after the ethanol injection. Conversely, ME were able to match the decrease in glucose Ra with comparable declines in glucose Rd resulting in blood glucose concentrations that did not differ from controls. Thus chronic alcohol consumption results in sex differences in whole-body glucose production and glucose regulation.

A. Vakili, K. Tayebi, M. R. Jafari, M. R. Zarrindast, and B. Djahanguiri.  Effect of ethanol on morphine state-dependent learning in the mouse: involvement of gabaergic, opioidergic and cholinergic systems.  Alcohol & Alcoholism 39(5):427-432, September/October 2004.

Summary: This study examined the effect in mice of acute administration of ethanol when it replaced morphine in a step-down passive avoidance task on the test day and the effects of antagonists of GABAergic,opioidergic, and cholinergic systems on ethanol's actions. Morphine (5 mg/kg, s.c.) was administered as pre-training and 24 hours later as pre-test drug, and the latencies were measured. Ethanol (0.125, 0.25, 1, and 2 g/kg, i.p.) was administered instead of pre-test morphine. Antagonists of GABAergic (bicuculline 0.5, 1, and 2 mg/kg, i.p.), opioidergic (naloxone 0.06, 0.25, and 1 mg/kg, i.p.), and cholinergic (atropine 0.625 and 1.25 mg/kg, i.p. and mecamylamine 0.5, 1, and 2 mg/kg, i.p.) systems were co-administered with ethanol (0.25 g/kg, i.p.) on the test day. Locomotor activity was measured as well. Pre-training morphine impaired memory on the test day; memory was restored when the same dose of morphine was used as pre-test drug. All four doses of ethanol replaced pre-test morphine and enhanced memory. This effect was prevented by all of the antagonists studied. No significant changes were seen in the locomotor activity of the animals treated with ethanol or antagonists compared to the proper controls. It was concluded that GABAergic, endogenous opioidergic, and cholinergic systems are involved in the memory recall improvement by ethanol when it replaced morphine on the test day.

Marc A. Schuckit and Tom L. Smith.  Changes over time in the self-reported level of response to alcohol.  Alcohol & Alcoholism 39(5):433-438, September/October 2004.

Summary: This study investigated whether the number of alcohol drinks needed for an effect decreases between the teens and age 40. Data were available from the 20-year follow-up of 202 men who had originally been chosen at age 20 as nonalcoholic subjects from families at high and low risk for alcoholism. The number of drinks required for effects was determined through the Self-Report of the Effects of Alcohol questionnaire (SRE) and included subjects' recollection of their intensity of reaction early in their drinking careers as well as recent response to alcohol at the 15- and 20-year follow-ups. Overall, there was a slight decrease in the drinks required for effects across the three time points which became significant when recent drinking and depressant medication use were evaluated as covariates. When nonalcoholic or light-drinking subjects were evaluated separately, the decrease in the number of drinks needed for effects was more prominent. Among heavier drinkers, there was an increase in the number of drinks required for effects over time. The findings were generally similar for men with and without alcoholic relatives. The results suggest that development of a more intense reaction to alcohol, or fewer drinks needed for an effect, with increasing age may only be relevant to lighter drinkers. Among heavier drinkers, the finding that more drinks are required for effects may be relatively stable over time.

A. Van Den Bruel, B. Aertgeerts, K. Hoppenbrouwers, M. Roelants, and F. Buntinx.  CUGE: A screening instrument for alcohol abuse and dependence in students.  Alcohol & Alcoholism 39(5):439-444, September/October 2004.

Summary: The CUGE questionnaire consists of four questions: Have you ever felt you ought to Cut down on drinking?; “Have you often driven Under the influence?; Have you ever felt bad or Guilty about your drinking?; “Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (Eye opener)? The CUGE has been described as a promising screening device for problem drinking in students. This cross-sectional study assessed the diagnostic value of this new questionnaire in a new and independent population of freshmen. The study participants were freshmen of the Catholic University of Leuven (Belgium). All students received a questionnaire containing the CUGE and the Composite International Diagnostic Interview Instrument (CIDI) as a reference test. The CUGE was found to have very high sensitivity (91%) and a reasonable specificity (76.3%) in this validation group. It was concluded that the CUGE is an excellent screening instrument in this student population. In addition, the CUGE is a short questionnaire requiring only yes or no answers, which makes it easy to apply as a part of broad routine questionnaires.

Gregory E. Skipper, Wolfgang Weinmann, Annette Thierauf, Patrick Schaefer, Gerhard Wiesbeck, John P Allen, Michael Miller, and Friedrich Martin Wurst.  Ethyl glucuronide: A biomarker to identify alcohol use by health professionals recovering from substance use disorders.  Alcohol & Alcoholism 39(5):445-449, September/October 2004.

Summary: Ethyl glucuronide (EtG), a direct metabolite of alcohol, offers an extended window for assessing drinking status (up to 5 days) in abstinence-based monitoring programs. Urine samples were obtained from 100 participants in a physician monitoring program and additional samples were subsequently obtained "for cause," "to verify positive urine alcohol, when drinking was denied," and "in high-risk individuals." All participants had signed contracts agreeing to remain abstinent from mood-altering drugs, including alcohol, and had agreed to random urine testing. EtG was determined using LC/MS-MS. The main outcome measure was urine specimens positive for EtG versus specimens positive based on standard testing for alcohol and other drugs. None of the initial 100 random urine samples was positive for alcohol using standard testing, but 7 were positive for EtG (0.5-196 mg/l), suggesting recent alcohol use. Subsequent EtG testing was performed clinically during the course of monitoring. Of the 18 tests performed to date, 8 of 8 performed "for cause" were positive for EtG but negative for all other drugs including urine alcohol; all were confirmed positive by self-reported drinking by the patient when confronted with the positive test result. Of 6 tests performed to "confirm a positive urine alcohol," 2 were positive for EtG and confirmed positive by self-reported drinking. For the other 4 samples, especially 2 from a diabetic, possible in vitro fermentation is discussed. The results suggest that the rate of unrecognized alcohol use among physicians in monitoring programs is higher than previously reported. These programs can be strengthened by Incorporating EtG testing into alcohol abstinence monitoring.

Nicholas S. Aberle, II, Larry Burd, Bonnie H. Zhao, and Jun Ren.  Acetaldehyde-induced cardiac contractile dysfunction may be alleviated by vitamin B1 but not by vitamins B6 or B12.  Alcohol & Alcoholism 39(5):450-454, September/October 2004.

Summary: Chronic alcohol exposure leads to a deficiency of group B vitamins and increased risk of alcoholic cardiomyopathy. This study examined the effect of group B vitamin supplementation on cardiac contractile dysfunction induced in rat ventricular myocytes by the alcohol metabolite acetaldehyde. Mechanical contractile properties were evaluated by an IonOptix SoftEdge® system. Protein damage and apoptosis were determined by protein carbonyl and caspase-3 assays respectively. Short-term (4-6 hours) culture of myocytes with acetaldehyde (10 µM) depressed peak shortening amplitude, maximal velocity of shortening/relengthening, and shortened duration of shortening but not duration of relengthening. Acetaldehyde exposure also enhanced protein carbonyl formation and apoptosis in ventricular myocytes. The acetaldehyde-induced mechanical defects, protein damage, and apoptosis were prevented by vitamin B1 (10 µM), an essential vitamin required for DNA synthesis and repair. Vitamin B6 (10 µM) attenuated acetaldehyde-induced impairment of shortening duration. Vitamin B12 (1 mM) attenuated acetaldehyde-induced reduction in maximal velocity of shortening/relengthening. Unlike vitamin B1, none of the other acetaldehyde-elicited alterations in myocyte mechanical function were affected by vitamin B6 or vitamin B12. Vitamin B6 and vitamin B12 partially, but significantly, attenuated the acetaldehyde-induced carbonyl formation without affecting acetaldehyde-induced apoptosis. The findings provide evidence that vitamin B1 supplementation may protect against acetaldehyde-induced cytotoxicity by preventing protein damage and apoptotic cell death in ventricular myocytes.

Kathryn Graham, Andrée Demers, Jürgen Rehm, and Gerhard Gmel.  Problems with the graduated frequency approach to measuring alcohol consumption: Results from a pilot study in Toronto, Canada.  Alcohol & Alcoholism 39(5):455-462, September/October 2004.

Summary: A telephone survey was used to evaluate advantages and disadvantages of the graduated frequency approach to assessing alcohol consumption. The approach asks about the frequency of alcohol consumption at mutually exclusive quantity levels (i.e. 12 or more drinks, at least 8 drinks but less than 12, etc.). The subjects were 464 adults aged 18 and older in Toronto, Canada, who were contacted by random digit dialing and given computer-assisted interviews. Respondents reported higher frequency and volume of drinking on the graduated frequency measure compared to overall and beverage-specific quantity-frequency type measures. However, at least 16% of graduated frequency responses included double-counting on frequency estimates. When these cases were excluded or corrected, differences between the graduated frequency and quantity-frequency measures mostly disappeared. Graduated frequency was superior to quantity-frequency measures for identifying heavy episodic drinkers, but had little advantage over the weekly recall method except for identifying very infrequent (i.e., less often than twice a month) heavy drinkers. Because the graduated frequency has a high rate of response errors in terms of measuring frequency of alcohol consumption, it was concluded that other combinations of measures, including alternate measures of heavy episodic drinking, should be considered.

Rosa Alati, Stuart Kinner, Jake M. Najman, Greg Fowler, Kerrianne Watt, and David Green.  Gender differences in the relationships between alcohol, tobacco and mental health in patients attending an emergency department.  Alcohol & Alcoholism 39(5):463-469, September/October 2004.

Summary: The nature of the association between usual alcohol consumption, tobacco use, and symptoms of anxiety and depression were examined in a cross-sectional survey of 812 patients aged 16-84 presenting for treatment over a 14-day period to an emergency department in Queensland, Australia. Measures included sociodemographic data; the Alcohol Use Disorders Identification Test (AUDIT) to measure moderate, hazardous, and harmful alcohol consumption; and the Hospital Anxiety and Depression Scale (HADS) to measure state anxiety and depression. Gender differences were evident. For men, there was a U-shaped relationship between alcohol consumption and anxiety/depression, and a linear association between smoking and anxiety. For women, alcohol consumption and anxiety/depression showed a more linear relationship, but there was no significant relationship between tobacco use and anxiety/depression. Thus there may be important gender differences in the relationships between alcohol consumption, tobacco use, and mental health status. This study supports previous evidence that the mental health status of non-drinkers is worse than that of moderate drinkers, but only among males.

---