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CORK Bibliography: Alcohol. Chronic Effects

79 citations. July 2007 to present

Prepared: June 2008

Akine Y; Kato M; Muramatsu T; Umeda S; Mimura M; Asai Y et al. Altered brain activation by a false recognition task in young abstinent patients with alcohol dependence. Alcoholism: Clinical and Experimental Research 31(9): 1589-1597, 2007. (62 refs.)

Background: Heavy alcohol intake induces both structural and functional changes in the central nervous system. Recent research developments converged on the idea that even in patients with alcohol dependence without apparent structural brain changes, some cognitive impairment exists, and associated functional change could be visualized by neuroimaging techniques. However, these data were from old (more than 50 years) patients using working memory and response inhibition tasks. Whether young abstinent patients show aberrant signs of brain activation is a matter of interest, specifically by the long-term memory retrieval task. Methods: Subjects were 9 young patients with alcohol dependence with long-term abstinent (8 males and 1 female) and age- and education-matched 9 healthy controls (7 males and 2 females). We used a modified false recognition task in a functional MRI study. Results: The young patients with alcohol dependence showed reduced activation in the right dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), left pulvinar in the thalamus, and in the right ventral striatum, although behavioral performances and regional patterns of brain activation were similar between patients and controls. Conclusions: Long-term memory retrieval induced altered activations in prefrontal lobes, ACC, thalamus, and ventral striatum in young patients with alcohol dependence. These findings were correspondent to deficits of goal directed behavior, monitoring the erroneous responses, memory function, and drug-seeking behavior. Furthermore, these reduced activations can be considered as latent "lesions," suggesting subclinical pathology in alcoholic brains.

Alexander-Kaufman K; Harper C; Wilce P; Matsumoto I. Cerebellar vermis proteome of chronic alcoholic individuals. Alcoholism: Clinical and Experimental Research 31(8): 1286-1296, 2007. (54 refs.)

Background: Cerebellar changes are commonly associated with alcoholism and chronic alcohol consumption can produce profound impairments in motor functioning and various aspects of cognition. Although the mechanisms underlying alcohol-induced changes in the cerebellar vermis are poorly understood, observations in the alcoholic vermis are thought to be consequential to common alcohol-related factors, particularly thiamine deficiency. Methods: In the present study, we used a proteomics-based approach to compare protein expression profiles of the cerebellar vermis from human alcoholic individuals (both neurologically uncomplicated and alcoholic individuals complicated with liver cirrhosis) and healthy control brains. This article complements our recent studies performed on alcoholic prefrontal gray and white matter and splenium of the corpus callosum (CC). Results: Like the CC study, several liver cirrhosis-specific proteins were identified in the vermis, perhaps indicating the effects of liver dysfunction in this brain region. Among other protein expression changes observed are disturbances in the levels of thiamine-dependent enzymes. A derangement in energy metabolism perhaps related to thiamine deficiency seems to be important in both alcoholic groups, even where there are no clinical or pathological findings of Wernicke-Korsakoff syndrome. Conclusions: These results suggest that clinically and pathologically uncomplicated alcoholic cases may not in fact be "uncomplicated," as at the proteome level we seem to be isolating the confounding effects of nutritional deficiencies and liver dysfunction and perhaps their role in alcohol-related vermis damage. Together, these results indicate that the alcohol-related pathology of the vermis is more multifactorial than other brain regions examined previously (prefrontal region and CC splenium).

Auguet T; Vidal F; Lopez-Dupla M; Broch M; Gutierrez C; Olona M et al. A study on the TNF-alpha system in Caucasian Spanish patients with alcoholic liver disease. Drug and Alcohol Dependence 92(1/3): 91-99, 2008. (56 refs.)

Background: Tumor necrosis factor-alpha (TNF-alpha) is thought to be a critical driving force of inflammatory damage in alcoholic liver disease (ALD). We aimed to establish whether there is a correlation between plasma levels of the soluble TNF-alpha receptors 1 and 2 (sTNFR1 and sTNFR2) and the severity of liver damage in patients with ALD. We also aimed to elucidate whether functionally active polymorphisms in the promoter region of the TNF-alpha gene modulate the development of ALD. Design: We studied 614 Spaniards. Of these, 278 were alcoholics (103 without liver histologic abnormalities, 89 with non-cirrhotic liver disease and 86 with cirrhosis) and 336 were non-alcoholics (115 healthy controls, 114 with non-alcoholic non-cirrhotic liver disease and 107 with cirrhosis unrelated to alcohol). Plasma levels of sTNFR1 and sTNFR2 were determined by ELISA and results were expressed in ng/mL and subsequently converted in log(10). TNF-alpha gene promoter region polymorphisms at the positions -238, -308 and -863 were assessed by restriction fragment length polymorphisms (RFLPs) on white cell DNA. Differences in plasma sTNFR1 and sTNFR2 levels between groups were compared with the one-way and two-factor analysis of variance test, and Student's t-test. Genotype distribution and allele frequencies in the different groups were compared using the chi(2) test or Fisher's exact test. Results: sTNFR1 and sTNFR2 plasma levels were significantly higher in patients with cirrhosis than in those with non-cirrhotic liver disease (p < 0.001) and individuals without liver disease (p < 0.001), both in the alcoholic and the non-alcoholic group. Among cirrhotics, sTNFR1 and sTNFR2 levels had a significant positive correlation with the severity of the liver disease, graded with the Child-Pugh's score (P = 0.003 and p < 0.001, respectively). TNF-alpha genotype distribution and allele frequencies of the three loci assessed were similar in the groups studied, hence no particular genotype or haplotype could be linked to ALD. Conclusions: The TNF-alpha system is activated in patients with cirrhosis of the liver irrespective of aetiology. TNF-alpha polymorphisms at positions -238, -308 and -863 are not linked to ALD.

Brand M. Cognitive profile of patients with alcoholic Korsakoff's syndrome. International Journal on Disability and Human Development 6(2): 161-170, 2007. (72 refs.)

Long lasting or excessive alcohol consumption can result in alcoholic Korsakoffs syndrome, characterized by severe anterograde and also retrograde memory deficits, as well as impairments in temporal orientation. In addition, further neuropsychological reductions can accompany the syndrome. Executive dysfunctions and emotional abnormalities are commonly reported in patients with Korsakoff's pathology but also seen in non-amnesic subjects with alcohol dependency. In patients with Korsakoff's syndrome, the additional deficits mentioned are most commonly less severely pronounced than are amnesic symptoms. For the cognitive decline in patients suffering from this disease, damage to diencephalic and prefrontal brain regions are the most prominent neural correlates. Most likely, lesions within the mammillary bodies and parts of the thalamus are responsible for memory deterioration, whereas prefrontal damage primarily contributes to executive dysfunctions. Still a topic of debate is whether the direct alcoholic neurotoxic effects causes the brain changes in patients with Korsakoff's pathology or whether malnutrition and thiamine deficiency, potentially influenced by a genetic predisposition, are more strongly related to the diencephalic lesions that might be specific for Korsakoff's syndrome. In the course of the disease, evidence suggests that cognitive impairments remain more or less stable over time. Therefore, the syndrome can be viewed as a single entity and it does not necessarily result in alcohol-related dementia.

Brust JCM. A 74-year-old man with memory loss and neuropathy who enjoys alcoholic beverages. Journal of the American Medical Association 299(9): 1046-1054, 2008. (103 refs.)

Adverse effects of alcohol on the peripheral and central nervous system can be direct ( ie, neurotoxicity) or indirect (eg, nutritional deficiency). Using the case of Mr E, an older, moderate to heavy drinker experiencing memory difficulty, the diagnostic considerations, which include mild cognitive impairment, early Alzheimer dementia, Wernicke-Korsakoff syndrome, and "alcoholic dementia," are discussed. These disorders are not mutually exclusive, and in a patient with either mild cognitive impairment or dementia, the contributory role of alcohol can be difficult to determine. In fact, epidemiological studies suggest that mild to moderate intake of alcohol actually reduces the risk of developing mild cognitive impairment or dementia, including Alzheimer dementia. Appropriate management includes measures to reduce alcohol dependence (eg, behavioral or pharmacological therapy) and to delay progression of the cognitive impairment (eg, engaging in healthy behaviors such as cognitive leisure activities).

Cairney S; Clough A; Jaragba M; Maruff P. Cognitive impairment in Aboriginal people with heavy episodic patterns of alcohol use. Addiction 102(6): 909-915, 2007. (45 refs.)

Background With chronic alcohol abuse, cognitive studies suggest that progressive cognitive decline may precede more serious and irreversible neurological syndromes. The early detection of cognitive impairment may therefore aid in the prevention of permanent brain damage. Despite the devastating consequences of alcohol abuse among Aboriginal Australians, the effects on brain function have never been studied in this population and a lack of appropriate assessment tools has prevented the development of such research. Aims To determine the impact of long-term and heavy episodic alcohol use on cognitive function in Aboriginal people. Design Cross-sectional comparing heavy episodic alcohol users with non-alcohol users. Setting Two remote Aboriginal communities in north-east Arnhem Land, northern Australia. Subjects The control group consisted of 24 non-drinkers (15 males, nine female) and the heavy episodic group consisted of 20 people (19 males, one female) who had been drinking alcohol in a heavy episodic style (median 14 drinks per occasion) for a mean of 8.9 years (SD = 5.0). Measurements Interview to obtain demographic information, substance abuse history and symptoms of mental health and wellbeing, together with a computerized cognitive assessment battery (CogState Ltd). Findings Compared with non-drinkers, heavy episodic drinkers showed reduced psychomotor speed (P = 0.04) and reduced accuracy when performing tasks of attention (P = 0.045), working memory (P = 0.04), implicit memory (P = 0.03) and associate learning and memory (P = 0.001). Conclusions Specific cognitive abnormalities that suggest frontostriatal abnormalities and have been observed in association with chronic alcoholism in other populations were observed among Aboriginal Australians who were heavy episodic alcoholic users.

Chick J; Kemppainen E. Estimating alcohol consumption. (review). Pancreatology 7(2/3): 157-161, 2007. (29 refs.)

Alcohol use is one of the two main aetiologies of acute pancreatitis. Detection of excessive alcohol consumption is problematic, illustrated by the fact that self-reports of alcohol consumption account for only approximately 50% of the reported sales of alcohol. To improve the reliability, structured questionnaires and various biochemical markers have been developed to estimate alcohol consumption objectively. Further, the pattern of drinking and level of consumption within the past 2 weeks may alter the clinical picture of the acute pancreatitis. The aim of this paper is to remind the clinician of the importance of accurate and complete history, the need to document the actual alcohol consumption, pattern of drinking, clinical signs of alcoholism and to use biochemical tests and sometimes questionnaires.

Choo EK; McElroy S. Spontaneous bowel evisceration in a patient with alcoholic cirrhosis and an umbilical hernia. Journal of Emergency Medicine 34(1): 41-43, 2008. (15 refs.)

We present a case of spontaneous intestinal evisceration through an umbilical hernia in a patient with alcoholic cirrhosis and long-standing ascites. Hernia rupture is an unusual and potentially life-threatening event in patients with tense ascites. Patients should be managed on an individual basis, balancing aggressive medical stabilization with the need for prompt surgical repair.

Christoffersen S. Death from seizures induced by chronic alcohol abuse - Does it exist? (review). Seizure 16(5): 379-383, 2007. (53 refs.)

In a forensic setting, deaths due to seizures, either epileptic or other, present a well-known problem. Cause of death is rarely established on the basis of physical evidence, but on circumstantial evidence such as tongue biting or discharge of urine or faeces. Seizures have several different aetiotogies, but in police reports a person known to have seizures is most likely to be reported as suffering from epilepsy. It is a well-known fact that alcoholics have seizures either due to "alcohol-induced epilepsy" or due to withdrawal from drinking. It also seems to be generally accepted that alcoholics may die from these seizures. A literature study was performed of deaths due to alcohol-induced seizures, either during withdrawal or as late-onset seizures where the aetiology was established as long time alcohol abuse and a necropsy had shown no other possible cause of death than a seizure. Results: It was not possible to find any well-documented cases. It is, however, difficult to compare cases in the literature, as there is no generally accepted classification or nomenclature of seizures related to alcohol abuse.

Chrostek L; Cylwik B; Krawiec A; Korcz W; Szmitkowski M. Relationship between serum sialic acid and sialylated glycoproteins in alcoholics. Alcohol and Alcoholism 42(6): 588-592, 2007. (27 refs.)

Aims: Total sialic acid (TSA) has been suggested as a marker for chronic alcohol abuse. It seems that the elevation of TSA during excessive alcohol consumption reflects the changes in sialylated glycoproteins in the sera. On the other hand, chronic ethanol consumption increases the desialylation rate of many serum glycoproteins. The aim of this study was to evaluate the relationship between the total and free form of sialic acid levels (FSA), and the concentration of sialylated glycoproteins in alcoholics. Methods: We determined the serum concentration of many glycoproteins (1-antitrypsin, 1-acid glycoprotein, haptoglobin, ceruloplasmin, transferrin, complement C3 protein, fibrinogen and immunoglobulin G) in a sample of 100 alcoholics and 30 healthy controls. Total sialic acid was determined by the enzymatic method and its free form by using a modification of the thiobarbituric acid method. Results: Among alcoholics, we found increased concentrations of 1-antitrypsin and 1-acid glycoprotein but decreased levels of transferrin. The concentrations of TSA and FSA were significantly higher in alcoholics than in healthy controls. The tested glycoproteins, except for transferrin and immunoglobulin G, positively correlated with TSA and FSA. The correlations with TSA were higher than that with FSA. Conclusions: Chronic alcohol abuse alters the concentrations of some sialylated glycoproteins in the sera. The 1-antitrypsin, 1-acid glycoprotein, and transferrin are the only affected glycoproteins. The serum level of total and free form of sialic acid in the sera of alcoholics depends on the concentration of the most sialylated glycoproteins.

Clark CP; Brown GG; Eyler LT; Drummond SPA; Braun DR; Tapert SF. Decreased perfusion in young alcohol-dependent women as compared with age-matched controls. American Journal of Drug and Alcohol Abuse 33(1): 13-19, 2007. (15 refs.)

Aim: To use the superior spatial resolution of magnetic resonance imaging (MRI) to examine differences in cerebral perfusion between young alcohol dependent and normal women. Methods: Eight alcohol dependent women and 8 controls (all ages 18-25) received single-slice resting perfusion-weighted MRI (directly proportional to brain blood flow), with slices located above the corpus callosum. Results: Alcohol-dependent women had decreased perfusion in prefrontal and left parietal regions. Conclusions: Reduced perfusion has not previously been reported in young, physically healthy alcohol dependent females, yet is consistent with previously reported decreased cerebral activity in alcohol dependence.

Clark US; Oscar-Berman M; Shagrin B; Pencina M. Alcoholism and judgments of affective stimuli. (review). Neuropsychology 21(3): 346-362, 2007. (101 refs.)

This study sought to differentiate alcoholism-related changes in judgments of emotional stimuli from those of other populations in which such changes have been documented. Two sets of visual stimuli, one containing words and the other containing drawings of faces (representing a range of emotional content), were presented to abstinent alcoholic adults with and without Korsakoff's syndrome, as well as to a healthy control group and four groups of patients with other neurobehavioral disorders: Parkinson's disease, schizophrenia, depression, and posttraumatic stress disorder. Participants rated the stimuli according to emotional valence and intensity of emotion. Results implicated bi-hemispheric frontal and subcortical involvement in the abnormalities of emotion identification associated with alcoholism, and they also support the notion of age-related vulnerabilities in conjunction with alcoholism.

Demirhan O; Tastemir D. Cytogenetic effects of ethanol on chronic alcohol users. Alcohol and Alcoholism 43(2): 127-136, 2008. (52 refs.)

Aim: Alcoholism is a significant public health problem that is also associated with a complex genetic trait. Fragile sites (FS) are potentially informative endpoints for the study of clinical disorders. We aimed to find chromosomal damages in chronic alcohol users for the purpose of finding the correlation between alcohol and chromosomal anomalies. Methods: The potential roles/effects of ethanol on chromosome(s) were assessed in this study by investigating its cytotoxic effects in lymphocyte cultures from chronic alcoholics and controls. Results: Alcoholics revealed a significantly higher frequency of FS and chromosomal aberrations (CA), and the FS clusters in specific chromosomal regions: 1q12, 1q21, 1q32, 2p13, 2q21, 2q31, 3p14, 3p25, 3q21, 4q21, 4q31, 5q31, 6p21, 7q22, 7q32, 9q13, 9q22, 10q22, 11q23, and 12q13. We also observed a significantly greater number of numerical and structural CA in alcoholics. The most frequent exchange types were deletions and polymorphic variations. CA could be due to the cumulative effect of both alcohol and smoking. The loci 1q12, 3p25, 4q31, 6p21, and 12q13 were not reported previously in alcoholics and may be hot spots for alcoholism. The overall FS frequencies were not statistically different between smoker and non-smoker controls, but smoking significantly increased the expression of 1p36, 3q21, and 5p15 sites. These sites have important clinical significance. Conclusions: Chronic alcohol abuse and the smoking habit can lead to chromosome damages that are especially influential on oncogenic regions, which may persist for a long time, and constitute a relevant factor of risk for the development of neoplasias.

Durazzo TC; Cardenas VA; Studholme C; Weiner MW; Meyerhoff DJ. Non-treatment-seeking heavy drinkers: Effects of chronic cigarette smoking on brain structure. Drug and Alcohol Dependence 87(1): 76-82, 2007. (61 refs.)

We previously reported [Cardenas, V.A., Studholme, C., Meyerhoff, D.J., Song, E., Weiner, M.W., 2005. Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes. Psychiatry Research. 138, 115-130] that non-treatment-seeking, active heavy drinkers (HD) demonstrated smaller regional neocortical gray matter volumes compared to light drinking controls; however, the potential effects of chronic cigarette smoking on regional brain volumes were not addressed. The goal of this retrospective analysis was to determine if chronic smoking affected brain structure in the non-treatment-seeking heavy drinking sample from our earlier report (i.e., Cardenas et al., 2005). Regional volumetric comparisons were made among age-matched smoking HD (n = 17), non-smoking HD (n = 16), and non-smoking light drinkers (nsLD; n = 20) from our original sample. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance imaging. Smoking HD demonstrated smaller volumes than nsLD in the frontal, parietal, temporal GM, and for total neocortical GM. Smoking HD also demonstrated smaller temporal and total GM volumes than non-smoking HD. Non-smoking HD and nsLD did not differ significantly on GM volumes. Further, the three groups did not differ on lobar WM, subcortical structures or regional CSF volumes. These retrospective analyses indicate neocortical GM volume reductions in non-treatment-seeking smoking HD, but not in non-smoking HID, which are consistent with our studies in recently detoxified treatment-seeking alcohol-dependent samples.

Durazzo TC; Gazdzinski S; Meyerhoff DJ. The neurobiological and neurocognitive consequences of chronic cigarette smoking in alcohol use disorders. (review). Alcohol and Alcoholism 42(3): 174-185, 2007. (108 refs.)

A vast body of research attests to the adverse effects of chronic smoking on cardiac, pulmonary, and vascular function as well as the increased risk for various forms of cancer. However, comparatively little is known about the effects of chronic smoking on human brain function. Although smoking rates have decreased in the developed world, they remain high in individuals with alcohol use disorders. Despite the high prevalence of comorbid chronic smoking in alcohol use disorders, very few studies have addressed the potential neurobiological or neurocognitive effects of chronic smoking in alcohol use disorders. Here, we briefly review the existing literature on the neurobiological and neurocognitive consequences of chronic cigarette smoking and summarize our neuroimaging and neurocognitive studies on the effects of comorbid chronic excessive alcohol consumption and cigarette smoking in treatment-seeking and treatment-naive populations. Our research suggests comorbid chronic cigarette smoking modulates magnetic resonance-detectable brain injury and neurocognition in alcohol use disorders and that neurobiological recovery in our abstinent alcoholics is adversely affected by chronic smoking. Consideration of the potential separate effects and interactions of chronic smoking and alcohol consumption may foster a better understanding of specific mechanisms and neurocognitive consequences of brain injury in alcoholism and of brain recovery during sustained abstinence from alcohol. The material presented also contributes to ongoing discussions about treatment strategies for comorbid alcoholism and cigarette smoking and will hopefully stimulate further research into the neurobiological and neurocognitive consequences of chronic smoking in alcoholism and other substance use disorders.

Durazzo TC; Meyerhoff DJ. Neurobiological and neurocognitive effects of chronic cigarette smoking and alcoholism. (review). Frontiers in Bioscience 12: 4079-4100, 2007. (296 refs.)

Chronic cigarette smoking is associated with adverse effects on cardiac, pulmonary, and vascular function as well as the increased risk for various forms of cancer. However, little is known about the effects of chronic smoking on human brain function. Although smoking rates have decreased in the developed world, they remain high in individuals with alcohol use disorders ( AUD) and other neuropsychiatric conditions. Despite the high prevalence of chronic smoking in AUD, few studies have addressed the potential neurobiological or neurocognitive consequences of chronic smoking in alcohol use disorders. Here, we review the the neurobiological and neurocognitive findings in both AUD and chronic cigarette smoking, followed by a review of the effects of comorbid cigarette smoking on neurobiology and neurocognition in AUD. Recent research suggests that comorbid chronic cigarette smoking modulates magnetic resonance-detectable brain injury and neurocognition in alcohol use disorders and adversely affects neurobiological and neurocognitive recovery in abstinent alcoholics. Consideration of the potential separate and interactive effects of chronic smoking and alcohol use disorders may have significant implications for pharmacological and behavioral treatment interventions.

Durazzo TC; Rothlind JC; Cardenas VA; Studholme C; Weiner MW; Meyerhoff DJ. Chronic cigarette smoking and heavy drinking in human immunodeficiency virus: Consequences for neurocognition and brain morphology. (review). Alcohol 41(7): 489-501, 2007. (115 refs.)

Alcohol use disorders (AUD) and chronic cigarette smoking are common among individuals with human immunodeficiency virus infection (HIV). Concurrent AUD in HIV is related to greater abnormalities in brain morphology and neurocognition than either condition alone. However, the potential influence of chronic smoking on brain morphology and neurocognition in those concurrently afflicted with AUD and HIV has not been examined. The goal of this retrospective analysis was to determine if chronic smoking affected neurocognition and brain morphology in a subsample of HIV-positive non-treatment-seeking heavy drinking participants (HD+) from our earlier work. Regional volumetric and neurocognitive comparisons were made among age-equivalent smoking HD+(n = 17), nonsmoking HD+ (n = 27), and nonsmoking HIV-negative light drinking controls (n = 27) obtained from our original larger sample. Comprehensive neuropsychological assessment evaluated multiple neurocognitive domains of functioning and for potential psychiatric comorbidities. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and sulcal and ventricular cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance images. The main findings were (1) smoking HD+ performed significantly worse than nonsmoking HD+ on measures of auditory-verbal (AV) learning, AV memory, and cognitive efficiency; (2) relative to controls, smoking HD+ demonstrated significantly lower neocortical GM volumes in all lobes except the occipital lobe, while nonsmoking HD+ showed only lower frontal GM volume compared with controls; (3) in the HD+ group, regional brain volumes and neurocognition were not influenced by viremia, highly active antiretroviral treatment, or Center for Disease Control symptom status, and no interactions were apparent with these variables or smoking status. Overall, the findings suggested that the direct and/or indirect effects of chronic cigarette smoking created an additional burden on the integrity of brain neurobiology and neurocognition in this cohort of HIV-positive heavy drinkers.

Durvasula RS. Alcohol use and neuropsychological performance in persons with HIV/AIDS. (review). International Journal on Disability and Human Development 6(4): 417-429, 2007. (56 refs.)

Both human immunodeficiency virus (HIV) and alcohol use contribute to neuropsychological (NP) impairment, and a relatively large proportion of HIV seropositive individuals have histories of heavy alcohol use. Evidence from neuropathological, and both structural and functional neuroimaging studies have supported the direct central nervous system effects of both HIV and alcohol. HIV preferentially affects frontal regions of the brain as well as subcortical structures including the basal ganglia, while alcohol has been shown to result in cortical atrophy and cerebellar and frontal damage. These central nervous system changes are clinically manifested through psychomotor slowing, memory impairments, slowed reaction time, and executive dysfunction in persons with HIV. Alcohol use and abuse are associated with similar deficits as well as dysfunction in domains including visuoperception. While some studies have observed a synergistic effect between alcohol and HIV on NP performance, particularly reaction time, this has not been consistent. Whether HIV and alcohol exert purely independent, additive or interactive NP effects remains unresolved, and this may in part be due to methodological issues inherent in the measurement of alcohol use, comorbidities such as substance use, and other co-factors, such as socioeconomic status and neurologic history. The picture of NP decline due to HIV continues to evolve in the era of highly active antiretroviral therapy (HAART), and it is still unclear whether such changes will mitigate the impact of alcohol on NP functioning in persons with HIV.

Fabricius K; Pakkenberg H; Pakkenberg B. No changes in neocortical cell volumes or glial cell numbers in chronic alcoholic subjects compared to control subjects. Alcohol and Alcoholism 42(5): 400-406, 2007. (40 refs.)

Aims: To study if the total glial cell population in the neocortex is intact in subjects with a history of severe alcohol abuse compared to control subjects. Further, to investigate whether the cortical nerve cell nuclei and nerve cell perikarya volumes are the same in chronic alcoholic subjects as in the control subjects. Methods: Using the stereological method, the optical rotator in a vertical design, the perikaryon cell volume and nuclei cell volume in the neocortex and its four subdivisions were studied in 11 alcoholics and 10 control subjects. Using the Cavalieri estimator of volumes and the optical disector for cell counting, we estimated the total number of glial cells in the neocortex and compared previous stereological results for chronic alcoholic subjects. Results: We found the mean neuronal cell volumes to be unaffected by severe alcohol abuse (p=0.84) and a normal total number of glial cells (p=0.39) in chronic alcoholic subjects compared to control subjects. Conclusion: Only glial cells and dendritic/synaptic changes have so far been reported in stereological studies of the brains of alcoholic subjects. We thus have increasing evidence that it may be possible for some individuals to return to their previous cognitive abilities after cessation of alcohol which may give hope and encouragement for chronic alcoholic subjects to stop the abuse.

Fan AZ; Russell M; Stranges S; Dorn J; Trevisan M. Association of lifetime alcohol drinking trajectories with cardiometabolic risk. Journal of Clinical Endocrinology and Metabolism 93(1): 154-161, 2008. (31 refs.)

Context and Objective: Alcohol intakes may vary considerably over a drinker's lifetime. This study was designed to examine whether lifetime drinking trajectories are associated with cardiovascular risk factors that are used to define the metabolic syndrome (MetS). Design, Setting, Participants, and Outcomes: This is a population-based cross-sectional study. Participants were ever-regular drinkers (n = 2818) selected from healthy controls for the Western New York Health Study (1996-2001) in which lifetime lifestyle was ascertained retrospectively. Prevalence of the MetS and its individual components, including obesity, high triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure, and high fasting glucose, were the main outcomes. Results: Trajectory analyses were based on estimates of total kilograms of ethanol for each age decade between 10 and 59 yr. Two groups of drinkers with distinct lifetime drinking trajectories were obtained, an early peak and a stable trajectory group. Compared with stable trajectory drinkers, early-peak drinkers were 10 yr younger on average, had earlier onset of regular drinking, drank heavily in late adolescence and early adulthood tapering off in middle age, averaged more drinks per drinking day in lifetime, and were more likely to abstain when interviewed. After controlling for age, sex, and other potential confounders, early-peak trajectories were modestly associated with high odds of the MetS [1.31; 95% confidence interval (CI) 1.00, 1.71] overall, low high-density lipoprotein cholesterol (1.62; 95% CI 1.27, 2.08), abdominal obesity(1.48; 95% CI 1.23, 1.78), and overweight (1.32; 95% CI 1.10, 1.60). Conclusion: Early initiation of alcohol drinking and heavy drinking in adolescence and early adulthood may be associated with an adverse cardiometabolic profile.

Fein G; McGillivray S. Cognitive performance in long-term abstinent elderly alcoholics. Alcoholism: Clinical and Experimental Research 31(11): 1788-1799, 2007. (84 refs.)

Background: To date, there is a wealth of literature describing the deleterious effects of active alcoholism on cognitive function. There is also a growing body of literature on the extent of cognitive recovery that can occur with abstinence. However, there is still a dearth of published findings on cognitive functioning in very long-term abstinence alcoholics, especially in the elderly population. Methods: The current study examines 91 elderly abstinent alcoholics (EAA) (49 men and 42 women) with an average age of 67.3 years, abstinent for an average of 14.8 years (range 0.5 to 45 years), and age and gender comparable light/nondrinking controls. The EAA group was divided into 3 subgroups: individuals that attained abstinence before age 50 years, between the ages 50 and 60 years, and after age 60 years. Attention, verbal fluency, abstraction/cognitive flexibility, psychomotor, immediate memory, delayed memory, reaction time, spatial processing, and auditory working memory were assessed. The AMNART and cranium size were used as estimates of brain reserve capacity, and the association of all variables with alcohol use measures was examined. Results: Overall, the EAA groups performed comparably to controls on the assessments of cognitive function. Only the abstinent in group before 50 years of age performed worse than controls, and this was only in the domain of auditory working memory. EAAs had larger craniums than their controls. This effect was strongest for those who drank the longest and had the shortest abstinence. Such individuals also performed better cognitively. Conclusions: Our data showed that elderly alcoholics that drank late into life, but with at least 6 months abstinence can exhibit normal cognitive functioning. Selective survivorship and selection bias probably play a part in these findings. Cognitively healthier alcoholics, with more brain reserve capacity, may be more likely to live into their 60s, 70s, or 80s of age with relatively intact cognition, and to volunteer for studies such as this. Our results do not imply that all elderly alcoholics with long-term abstinence will attain normal cognition.

Ferdinandis TGHC; De Silva HJ. Illicit alcohol consumption and neuropathy: A preliminary study in Sri Lanka. Alcohol and Alcoholism 43(2): 171-173, 2008. (15 refs.)

Aims: To compare the effects on peripheral and autonomic nerve functions of Sri Lankan illicitly distilled alcohol consumption versus legal spirit consumption. Methods: Peripheral nerve conduction and autonomic nerve functions were assessed in 40 healthy control subjects and two groups of chronic heavy drinkers: 41 illicit spirit drinkers and 17 legal spirit drinkers. Results: Lower-limb motor and sensory nerve conduction parameters were affected in both groups of alcoholics. When compared with controls, in illicit spirit drinkers the mean heart rate indexes of all parasympathetic tests were lower while in legal spirit drinkers the heart rate response to standing was affected. There were no differences in the results of the above tests when the two groups of heavy drinkers were compared. Conclusions: Though chronic alcoholism results in peripheral and autonomic nerve damage, the damage caused by consumption of illicitly distilled spirit is not worse than the damage caused by consumption of legal spirits.

Fernandez-Torre JL; Martinez-Martinez M. Non-convulsive status epilepticus as an unrecognized cause of acute confusion in alcoholics. (letter). European Journal of Neurology 14(8): E14-E15, 2007. (5 refs.)

Fitzpatrick LE; Jackson M; Crowe SF. The relationship between alcoholic cerebellar degeneration and cognitive and emotional functioning. Neuroscience and Biobehavioral Reviews 32(3): 466-485, 2008. (274 refs.)

Although it is now widely acknowledged that the cerebellum contributes to the modulation of higher-order cognitive and emotional functions, this relationship has not been extensively explored in perhaps the largest group of individuals with cerebellar damage, chronic alcoholics. Localised damage to the cerebellum has been associated with a specific constellation of deficits and has been termed the cerebellar cognitive affective syndrome' (CCAS) [Schmahmann, J.D., Sherman, J.C., 1998. The cerebellar cognitive affective syndrome. Brain 121, 561-579]. The CCAS describes a profile of impairments, including deficits in executive functioning and visuospatial skills, language disruption and altered personality and affective behaviour. It is conceivable that the CCAS may also develop in a subgroup of alcoholics with alcoholic cerebellar degeneration and may in part account for a proportion of the cognitive and affective deficits commonly observed with the condition. While evidence has emerged supporting such a relationship, methodological limitations and the lack of theoretically driven investigation of the contribution of cerebellar dysfunction to cognitive and emotional functioning in chronic alcoholics, preclude definitive conclusions being drawn.

Foisy ML; Kornreich C; Fobe A; D'Hondt L; Pelc I; Hanak C et al. Impaired emotional facial expression recognition in alcohol dependence: Do these deficits persist with midterm abstinence? Alcoholism: Clinical and Experimental Research 31(3): 404-410, 2007. (41 refs.)

Background: Emotional facial expression (EFE) decoding has been repetitively shown to be impaired in alcoholic inpatients. The present study aimed to replicate and extend previous findings on EFE recognition deficits in alcoholism. Methods: Alcoholic and control participants' performances were compared on an EFE decoding task with a transversal and a longitudinal design. More specifically, 49 alcoholic individuals were recruited at a long-stay postdetoxification treatment center at the third or fourth week of their detoxification process. Twenty-two of them [abstinent alcoholic participants (AA)] were met at the end of their hospitalization process, 2 months later. The 27 remaining patients [dropping alcoholic participants(AD)] dropped out from treatment before the second meeting. A control group (C) of 22 participants was constituted, and assessed twice with the same average time as AA between the 2 assessments. The 3 groups were similar regarding age, sex, and education level. Participants were presented at both times with an EFE decoding test consisting of 16 photographs depicting EFE of happiness, anger, disgust, and sadness. Results: The results corroborated previous findings highlighting more EFE decoding deficits in alcoholic participants compared with control participants, with no improvement after 3 months of abstinence. Transversal analyses further evidenced more EFE decoding difficulties in AD than in AA compared with controls. Conclusions: EFE decoding deficits in alcoholism persist with midterm abstinence. Alcoholic patients who dropped from treatment had the worst EFE decoding performance at baseline. Emotional facial expression decoding deficit could have a prognostic value in alcohol dependence.

Foisy ML; Kornreich C; Petiau C; Parez A; Hanak C; Verbanck P et al. Impaired emotional facial expression recognition in alcoholics: Are these deficits specific to emotional cues? Psychiatry Research 150(1): 33-41, 2007. (26 refs.)

Previous studies have repeatedly linked alcoholism is to impairment in emotional facial expression decoding. The present study aimed at extending previous findings while controlling for exposure times of stimuli. Further, a control task was added on the decoding of non-emotional facial features. Twenty-five alcoholic participants were compared to 26 control participants matched for age, sex and educational level. Participants performed two computer tasks consisting of presentation of photographs of faces for either 250 or 1000 iris. The first task required "yes" or "no" responses as rapidly as possible to questions regarding non-emotional features of the face (gender, age range and cultural identity). The second task involved a different set of photographs implicating emotional facial expression decoding, with the same exposure times. Again, rapid "yes" or "no" responses to trials combining 32 emotional facial expressions by eight emotional labels (happiness, sadness, fear, anger, disgust, surprise, shame, and contempt) were required from participants. Reaction times were recorded for both tasks. Alcoholic and control participants showed similar results in both tasks in terms of response accuracy. Yet, in the emotional facial expression task, alcoholic participants' responses matched more negative emotional labels, especially sadness. Further, alcoholics were slower than control participants specifically to answer emotional questions on emotional facial expression. No differences appeared on reaction times in the control task. Contrary to expectations, no interaction of stimulus time exposure and group was observed. Overall, these findings replicate and extend previous results on emotional facial expression decoding ability: Alcoholics are specifically impaired on emotional nonverbal behavior information processing: They are slower to correctly identify an emotion.

Franken IHA; Nijs IMT; Muris P; Van Strien JW. Alcohol selectively reduces brain activity during the affective processing of negative information. Alcoholism: Clinical and Experimental Research 31(6): 919-927, 2007. (46 refs.)

Background: Although it has frequently been suggested that alcohol influences emotions such as anxiety and fear through the modulation of affective information processing, few studies addressed this topic using objective measures. Objectives: The acute effects of alcohol on affective processing of pictorial stimuli were investigated using electrophysiological measures. Methods: Event-related brain potentials (ERP) resulting from watching pleasant, unpleasant, and neutral pictures were investigated in a group of participants receiving a beverage containing a moderate dose of alcohol (n=26) and a group of participants receiving a nonalcoholic placebo beverage (n=24). Both early [early posterior negativity (EPN)] and late [late positive potential (LPP)] ERP components were employed as index of emotional processing. Results: The results show that alcohol reduced brain activity during watching unpleasant information in a late stage (700-1000 ms). This suggests that alcohol selectively influences the processing of unpleasant information. Conclusions: The findings are in concordance with theories linking alcohol administration to decreased processing of affective information. The results are discussed in the context of the role of the effect of alcohol on affective information processing, and its relevance to alcoholism.

Garci-Valdecasas-Campelo E; Gonzalz-Reimers E; Santolaria-Fernandez F; de le Vega-Prieto MJ; Milena-Abril A; Sanchez-Perez MJ et al. Brain atrophy in alcoholics: Relationship with alcohol intake, liver disease, nutritional status, and inflammation. Alcohol and Alcoholism 42(6): 533-538, 2007. (37 refs.)

Objectives: Brain atrophy is a common finding in alcoholics. Several mechanisms may be involved, including ethanol itself, malnutrition, liver failure, and, possibly, ethanol-induced hormone and cytokine changes. The aim of this study was to analyse the relation of brain atrophyassessed by computerized tomography (CT) scanand the aforementioned alterations. Methods: Serum insulin-like growth factor 1 (IGF-1), interleukin (IL)-6, IL-8, IL-10, TNF alpha, PTH, estradiol, free testosterone, and corticosterone were measured in 36 alcoholics, ten of them cirrhotics, who also underwent brain CT, which recorded the presence of cortical atrophy or cerebellar atrophy, Evans, Huckmanns, cella media, bicaudate, cortical atrophy, bifrontal, and ventricular indices, and diameter of the third ventricle; subjective nutritional assessment, midarm anthropometry, and evaluation of liver function. Results: Patients showed marked alterations of all the CT indices compared with 12 controls, but poor relations between these indices and the other parameters analysed (IGF-1, handgrip strength and years of addiction with bifrontal index (P0.025 in all cases); PTH and Evans index (r=0.36, P=0.032); mean corpuscular volume with cella index and cortical atrophy (P0.05). Cerebellar atrophy was associated with a greater daily ethanol consumption (t=2.19, P=0.034). Conclusion: Brain atrophy is frequently observed in alcoholics, but relationships with liver function, cytokines, nutritional status, and hormone levels are poor.

Gazdzinski S; Durazzo TC; Weiner MW; Meyerhoff DJ. Are treated alcoholics representative of the entire population with alcohol use disorders? A magnetic resonance study of brain injury. Alcohol 42(2): 67-76, 2008. (67 refs.)

Almost all we know about neurobiological brain injury in alcohol use disorders has been derived from convenience samples of treated alcoholics. Recent research has demonstrated more comorbid conditions, poorer psychosocial functioning, and higher dependence levels in treated alcoholics than in their treatment-naive counterparts. Thus, it is not clear whether neuroimaging results from convenience samples of treated alcoholics can be generalized to the entire population with alcohol use disorders. We compared 35 treated alcoholics at I week of abstinence (ALC) and 32 treatment-naive heavy drinkers (HD) on regional brain volumes and metabolite concentrations obtained by in vivo magnetic resonance at 1.5 Tesla to evaluate for potential group differences. Then, we evaluated whether comorbid cigarette smoking and common demographic and clinical variables mediated any existing neurobiological group differences. ALC demonstrated smaller lobar gray matter volumes and thalami than HD, exacerbated by chronic smoking. Furthermore, concentrations of N-acetyl-aspartate (an accepted marker of neuronal viability), choline-containing metabolites (involved in membrane turnover), and myo-inositol (a putative marker of glial cells and osmolyte) were lower in multiple brain regions of ALC compared to HD. The lower N-acetyl-aspartate concentrations in white matter of ALC versus HD were explained by average number of drinks per month over the year preceding study. However, the other group differences were not explained by common drinking, demographic, and clinical variables (used as covariates at the same time) or by excluding participants with comorbid mood disorders. Taken together, this suggests that the degree of brain atrophy, as well as neuronal and membrane injury in clinical samples of alcoholics cannot be generalized to the much larger population with alcohol use disorders that does not seek treatment.

Graham AW; Schultz TK; Mayo-Smith MF; Ries RK; Wilford BB, eds. Principles of Addiction Medicine. Chevy Chase MD: American Society of Addiction Medicine, 2003. (Chapter refs.)

This volume is a comprehensive text on addictions. It is organized into 14 major sections, each of which has multiple chapters. There are over 200 contributors. The sections deal with the following themes: basic science and core concepts; pharmcology; diagnosis, assessment and early intervention; overview of addiction treatment; management of intoxication and withdrawal; pharmacologic interventions; behavioral interventions; 12-step programs and other recovery-oriented interventions; alcohol and drug problems in the workplace; medical disorders and complications of addiction; co-occurring addictive and psychiatric disorders; pain and addiction; and children and adolescents. There are also six appendices.

Holder HD. Liver cirrhosis in eastern Europe. (editorial). Addiction 102(8): 1178-1178, 2007. (6 refs.)

Horiguchi N; Ishac EJN; Gao B. Liver regeneration is suppressed in alcoholic cirrhosis: Correlation with decreased STAT3 activation. Alcohol 41(4): 271-280, 2007. (43 refs.)

Liver regeneration is suppressed in alcoholic patients; however, the underlying mechanisms are not fully understood. We examined liver regeneration and signal transducer and activator of transcription 3 (STAT3) activation (an important signal for liver regeneration) in cirrhotic livers from alcoholics, hepatitis C virus (HCV) infection, and alcoholic plus HCV infection. Liver regeneration and STAT3 activation were determined by immunohistochemistry analysis of Ki67 and STAT3 phosphorylation, respectively, in 20 alcoholic cirrhosis, 13 HCV ciffhosis, 13 alcoholic + HCV cirrhosis. Alcoholic or alcoholic plus HCV cirrhotic livers had significantly lower Ki67(+) and phospho-STAT3(+) (pSTAT3(+)) hepatocytes and bile duct cells than HCV cirrhotic livers. The pSTAT3 positive staining did not correlate with liver injury (elevation of serum levels of aspartate transaminase [AST] and alkaline phosphatase [ALP]) but correlated positively with cell proliferation (Ki67 positive staining). In conclusion: liver regeneration is suppressed in alcoholic cirrhotic livers, which may be partly due to decreased STAT3 activation

Jang DP; Namkoong K; Kim JJ; Park S; Kim IY; Kim SI et al. The relationship between brain morphometry and neuropsychological performance in alcohol dependence. Neuroscience Letters 428(1): 21-26, 2007. (41 refs.)

The aim of this study was to explore local brain atrophy of patients with alcohol dependence using a voxel-based analysis of magnetic resonance images and to investigate the relationship of those atrophic regions with drinking history and neuropsychological performances. Statistical parametric mapping was applied for the global and regional comparison of segmented gray matter and white matter images from 20 patients with alcohol dependence and with those from 20 controls. The Rey auditory-verbal learning test, Rey-Osterrieth complex figure test, Stroop test, trail-making test, and Wisconsin card sorting test were conducted as neuropsychological evaluations. There was a significant decrease in both gray matter and white matter globally in alcohol dependence. Bilateral parahippocampal white matter areas were reduced in particular. Perseverative responses and perseverative errors in the Wisconsin card sorting test had significant correlation with the decrease of gray matter decrease including the left superior temporal gyri and right postcentral region. The psychological performance measures correlated with gray matter rather than white matter, whereas right temporal white matter correlated with drinking amount for last 4 weeks. This may imply that alcohol consumption in heavy amounts damages both gray matter and white matter, and gray matter atrophy mainly leads to cognitive impairment, whereas white matter is related to drinking history.

Joshi PC; Guidot DM. The alcoholic lung: Epidemiology, pathophysiology, and potential therapies. American Journal of Physiology. Lung Cellular and Molecular Physiology 292(4): L813-L823, 2007. (84 refs.)

Epidemiological evidence gathered only in the past decade reveals that alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome by as much as three- to fourfold. Experimental models and clinical studies are beginning to elucidate the mechanisms underlying this previously unrecognized association and are revealing for the first time that chronic alcohol abuse causes discrete changes, particularly within the alveolar epithelium, that render the lung susceptible to acute edematous injury in response to sepsis, trauma, and other inflammatory insults. Recent studies in relevant animal models as well as in human subjects are identifying common mechanisms by which alcohol abuse targets both the alveolar epithelium and the alveolar macrophage, such that the risks for acute lung injury and pulmonary infections are inextricably linked. Specifically, chronic alcohol ingestion decreases the levels of the antioxidant glutathione within the alveolar space by as much as 80-90%, and, as a consequence, impairs alveolar epithelial surfactant production and barrier integrity, decreases alveolar macrophage function, and renders the lung susceptible to oxidant-mediated injury. These changes are often subclinical and may not manifest as detectable lung impairment until challenged by an acute insult such as sepsis or trauma. However, even otherwise healthy alcoholics have evidence of severe oxidant stress in the alveolar space that correlates with alveolar epithelial and macrophage dysfunction. This review focuses on the epidemiology and the pathophysiology of alcohol-induced lung dysfunction and discusses potential new treatments suggested by recent experimental findings.

Kaerlev L; Dahl S; Nielsen PS; Olsen J; Hannerz H; Jensen A et al. Hospital contacts for chronic diseases among Danish seafarers and fishermen: A population-based cohort study. Scandinavian Journal of Public Health 35(5): 481-489, 2007. (31 refs.)

Objectives: Seafarers' and fishermen's working conditions may impact on their lifestyle and health. Standardized hospital contact ratios (SHCRs) were compared in two time periods and the relative risks of hospital contact as a function of employment time were estimated. Methods: Cohorts of all Danish seafarers (officers and non-officers) registered by the Danish Maritime Authority (DMA) 1989-98 and fishermen retrieved from a pension registry 1989-98 were linked to the nationwide Occupational Hospitalization Registry (OHR) and followed up for incident diseases in two five-year time periods, from 1 January 1994 and 1 January 1999, respectively, using rates specific for age and calendar time for the entire Danish workforce as a reference. Results: The SHCRs for lung and cardiovascular diseases were high for non-officers. Among male officers, the SHCR for diabetes was high in the 1999 cohort and the SHCR for chronic heart diseases was statistically significantly higher in the 1999 than in the 1994 cohort. For both time periods high SHCR values were found for bronchitis, emphysema, cancer of the lung, alcohol-related liver diseases, and diabetes among male non-officers, and lung cancer among male officers. Among female non-officers, a high SHCR for skin melanomas was seen. Among fishermen high SHCRs for bronchitis, emphysema, lung cancer, and Raynaud's syndrome were found in both cohorts. No duration response pattern was observed in any of the analyses, which may reflect health-and lifestyle-related selection into the trades or a healthy worker effect. Conclusions: Danish seafarers, especially short-term employees, had an elevated risk of hospitalization for lifestyle-related diseases.

Kapaki E; Paraskevas GP; Theotoka I; Liappas I. Neurochemical profile of elderly alcoholic patients with cognitive decline compared with patients with other dementias. International Journal on Disability and Human Development 6(2): 215-223, 2007. (58 refs.)

Alcoholism may result in impaired cognition and dementia. The increased risk of dementia in older individuals interferes with the differential diagnosis, especially when an elderly patient with a long history of alcohol abuse is the case. The aim of the present study was to evaluate the diagnostic value of the putative cerebrospinal fluid (CSF) biomarkers tau, beta-amyloid 1-42 (A beta 42) and their ratio in differentiating alcohol related dementia (ARD) from others of vascular or degenerative aetiology. Double-sandwich ELISAs (Innotest htau antigen and beta-Amyloid (142), Innogenetics) were used to quantify the above markers in a total of 151 patients and 82 controls. Patient groups comprised: 24 ARD, 17 vascular dementia, I I dementia with Lewy bodies, 23 frontotemporal dementia and 76 Alzheimer's disease (AD) patients. Tau protein succeessfully differentiated ARD from AD with 88% specificity and 86% sensitivity. A beta 42 alone had a specificity of 86% and a sensitivity of 70%, while tau/A beta 42 ratio was better than tau alone with corresponding values 100% and 91% respectively. For the discrimination of ARD from other dementias the diagnostic value of the above markers is substantially lower. In conclusion, the combined use of CSF tau and A beta 42 seems to be a useful tool in the differential diagnosis of ARD from AD, while in other primary dementias only a positive result may be useful.

Kapasova Z; Szumlinski KK. Strain differences in alcohol-induced neurochemical plasticity: A role for accumbens glutamate in alcohol intake. Alcoholism: Clinical and Experimental Research 32(4): 617-631, 2008. (90 refs.)

Background: Repeated alcohol administration alters nucleus accumbens (NAC) basal glutamate content and sensitizes the capacity of alcohol to increase NAC extracellular glutamate levels. However, the relevance of alcohol-induced changes in NAC glutamate for alcohol drinking behavior is under-investigated. Methods: To examine the relationship between genetic variance in alcohol consumption and alcohol-induced neuroadaptations within the NAC, in vivo microdialysis was conducted in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA2/J (D2) mouse strains on injections 1 and 8 of repeated alcohol treatment (8 x 2 g/kg, IP). To confirm an active role for NAC glutamate in regulating alcohol drinking behavior, the glutamate reuptake inhibitor DL-threo-beta-benzyloxyaspartic acid (TBOA) (300 mu M) and the Group 2 metabotropic glutamate autoreceptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) (50 mu M) were infused into the NAC of B6 and D2 mice prior to alcohol consumption in a 4 bottle-choice test. Results: While strain differences were not apparent for NAC basal levels of dopamine, serotonin or gamma-amino butyric acid (GABA), repeated alcohol treatment elevated NAC basal glutamate content only in B6 mice. Strain differences in both the acute and the sensitized neurochemical responses to 2 g/kg alcohol were observed for all neurotransmitters examined. While the alcohol-induced rise in NAC dopamine and glutamate levels sensitized in B6 mice, a sensitization was not observed in D2 animals. Moreover, B6 mice exhibited a sensitized serotonin and GABA response to alcohol followed repeated treatment, whereas neither tolerance nor sensitization was observed in D2 animals. An intra-NAC APDC infusion reduced alcohol intake in both B6 and D2 mice by approximately 50%. In contrast, TBOA infusion elevated alcohol intake selectively in B6 mice. Conclusions: These data indicate an active role for NAC glutamate in regulating alcohol consumption in mice and support the hypothesis that predisposition to high alcohol intake involves genetic factors that facilitate alcohol-induced adaptations in glutamate release within the NAC.

Kapur BM; Vandenbroucke AC; Adamchik Y; Lehotay DC; Carlen PL. Formic acid, a novel metabolite of chronic ethanol abuse, causes neurotoxicity, which is prevented by folic acid. Alcoholism: Clinical and Experimental Research 31(12): 2114-2120, 2007. (73 refs.)

Background: Methanol is endogenously formed in the brain and is present as a congener in most alcoholic beverages. Because ethanol is preferentially metabolized over methanol (MeOH) by alcohol dehydrogenase, it is not surprising that MeOH accumulates in the alcohol-abusing population. This suggests that the alcohol-drinking population will have higher levels of MeOH's neurotoxic metabolite, formic acid (FA). FA elimination is mediated by folic acid. Neurotoxicity is a common result of chronic alcoholism. This study shows for the first time that FA, found in chronic alcoholics, is neurotoxic and this toxicity can be mitigated by folic acid administration. Objective: To determine if FA levels are higher in the alcohol-drinking population and to assess its neurotoxicity in organotypic hippocampal rat brain slice cultures. Methods: Serum and CSF FA was measured in samples from both ethanol abusing and control patients, who presented to a hospital emergency department. FA's neurotoxicity and its reversibility by folic acid were assessed using organotypic rat brain hippocampal slice cultures using clinically relevant concentrations. Results: Serum FA levels in the alcoholics (mean +/- SE: 0.416 +/- 0.093 mmol/l, n = 23) were significantly higher than in controls (mean +/- SE: 0.154 +/- 0.009 mmol/l, n = 82) (p < 0.0002). FA was not detected in the controls' CSF (n = 20), whereas it was > 0.15 mmol/l in CSF of 3 of the 4 alcoholic cases. Low doses of FA from 1 to 5 mmol/l added for 24, 48 or 72 hours to the rat brain slice cultures caused neuronal death as measured by propidium iodide staining. When folic acid (1 mu mol/l) was added with the FA, neuronal death was prevented. Conclusions: Formic acid may be a significant factor in the neurotoxicity of ethanol abuse. This neurotoxicity can be mitigated by folic acid administration at a clinically relevant dose.

Kim SY; Breslow RA; Ahn J; Salem N. Alcohol consumption and fatty acid intakes in the 2001-2002. National Health and Nutrition Examination Survey. Alcoholism: Clinical and Experimental Research 31(8): 1407-1414, 2007. (43 refs.)

Background: Alcohol consumption has the potential to affect dietary intakes of nutrients; however, little is known about fatty acid intakes among alcohol consumers in the U.S. population. Method: We examined the relation between self-reported alcohol consumption and dietary fatty acid intake in 4,168 adults in the cross-sectional National Health and Nutrition Examination Survey 2001-2002. Fatty acid intake was determined from a single, interviewer-administered 24-hour recall. The adjusted, weighted mean level of dietary fatty acid intakes, as characterized by nutrient density, was calculated as grams of fatty acid per 1,000 kcal of energy consumed according to average daily alcohol consumption and binge-drinking episodes. Results: Energy intake showed a significant increasing trend across alcohol consumption categories in both genders and binge-drinking categories in men. Women binge drinkers also showed a higher energy intake compared with nonbinge drinkers. Among men, decreased nutrient densities of saturated, monounsaturated, polyunsaturated, linoleic, and alpha-linolenic acids were associated with increasing alcohol consumption. Binge-drinking men but not women had significantly decreased intakes of total saturates, monounsaturates, polyunsaturates and linoleic, alpha-linolenic, eicosapentaenoic, and docosahexaenoic acid. When alcohol energy was excluded from calculation of nutrient densities, the results were similar to those with alcohol energy included, except that total saturated and monounsaturated fatty acid differences were no longer significant. In addition, there was an inverse relationship among men between binge-drinking frequency and total polyunsaturates, linoleic, alpha-linolenic, and eicosapentaenoic acids. Conclusions: Our cross-sectional results suggest that alcohol consumption may impact the dietary intake of essential fatty acids (EFAs). Given the public health importance of both alcohol consumption and intakes of EFAs, prospective studies of the relation should be considered.

Knudtson MD; Klein R; Klein BEK. Alcohol consumption and the 15-year cumulative incidence of age-related macular degeneration. American Journal of Ophthalmology 143(6): 1026-1029, 2007. (14 refs.)

Purpose: To investigate alcohol consumption as a risk factor for the 15-year cumulative incidence and progression of age-related macular degeneration (AMD). Design: Prospective population,based study in Beaver Dam, WI with four examinations at five year intervals initiated in 1988 (n = 3,509 contributed data for this analysis). Methods: History of alcohol consumption was obtained via questionnaire. Cumulative incidence of early AMD, exudative AMD, pure geographic atrophy, and progression of AMD were assessed from fundus photographs taken at each examination. Results: Heavy drinking (four or more drinks daily) at baseline was related to the 15-year cumulative incidence of pure geographic atrophy in men (odds ratio, 9.2; 95% confidence interval, 1.7 to 51.2). There were no consistent associations with the amount of beer, wine, or liquor consumption and the incidence or progression of AMD. Conclusions: Alcohol consumption is unlikely to strongly increase (or decrease) the risk of AMD.

Lange RT; Iverson GL; Franzen MD. Short-term neuropsychological outcome following uncomplicated mild TBI: Effects of day-of-injury intoxication and pre-injury alcohol abuse. Neuropsychology 21(5): 590-598, 2007. (67 refs.)

Research suggests that individuals who are intoxicated at the time of traumatic brain injury (TBI) have worse cognitive outcome compared with those who are sober. Worse outcome in patients with day-of-injury intoxication might (a) be related to the increased magnitude of brain injury resulting from a variety of negative responses not present following TBI in nonintoxicated individuals, or (b) reflect the effect of pre-injury alcohol abuse that is prevalent in individuals intoxicated at the time of injury. Most studies in this area have focused on patients with moderate to severe TBIs, and on medium- to long-term neuropsychological outcome. The purpose of this study was to examine the relative contributions of day-of-injury intoxication versus pre-injury alcohol abuse on short-term cognitive recovery following mild TBI. Participants were 169 patients with uncomplicated mild TBIs who were assessed on 13 cognitive measures within 7 days postinjury. The prevalence of intoxication at the time of injury was 54.4%. The prevalence of possible pre-injury alcohol abuse was 46.2%. Overall, the results suggest that pre-injury alcohol abuse, compared with day-of-injury alcohol intoxication, had the most influence on short-term neuropsychological outcome from uncomplicated mild TBI. However, the influence of pre-injury alcohol abuse was considered small at best.

Liappas I; Theotoka I; Kapaki E; Ilias I; Paraskevas GP; Soldatos CR. Neuropsychological assessment of cognitive function in chronic alcohol-dependent patients and patients with Alzheimer's disease. In Vivo 21(6): 1115-1118, 2007. (18 refs.)

Background: Heavy and chronic alcohol dependence and Alzheimer's disease may share some neuropsychological characteristics. Patients and Methods: The pattern of neuropsychological characteristics of 33 alcohol-dependent patients who reported memory disturbances were evaluated and compared to the neuropsychological performance of 38 patients with mild-stage Alzheimer's disease and 73 healthy subjects, serving as controls. Alcohol-dependent patients were examined with tools concerning the pattern Of alcohol abuse and problems related to alcohol consumption. All groups completed a full battery of neuropsychological tests for the assessment of cognitive functions, such as different kinds of memory, attention, executive function etc. Results: Alcohol-dependent patients fared worse compared to the control subjects in every test used. The comparison of alcohol-dependent patients versus patients with Alzheimer's disease showed that the latter are much more burdened, as far as cognition is concerned, in all aspects of memory. Conclusion: Alcohol-dependent patients, even if they are not demented, have mild cognitive impairment in all domains of cognition (memory and frontal functions) in comparison with controls which performed within the norms. Verbal fluency, working memory and frontal functions were impaired at the same degree in alcohol-dependent patients and in patients with Alzheimer's disease. Memory problems were more pronounced in Alzheimer's disease patients.

Liu JW; Lewohl JM; Harris RA; Dodd PR; Mayfield RD. Altered gene expression profiles in the frontal cortex of cirrhotic alcoholics. Alcoholism: Clinical and Experimental Research 31(9): 1460-1466, 2007. (47 refs.)

Background: Cirrhosis is the result of chronic liver disease that causes scarring and dysfunction of the liver. The disease is a common concomitant condition resulting from sustained exposure to alcohol. Heavy alcohol use results in brain damage that is generally more severe in cirrhotic compared with noncirrhotic alcoholics. We examined, at the cellular level, gene expression in the frontal cortex of cirrhotic alcoholics. Methods: Gene expression profiles were compared between cirrhotic and noncirrhotic alcoholics using similar to 47,000 element cDNA microarrays. Results: Widespread differences in transcriptome patterns were observed in cirrhotic compared with noncirrhotic alcoholics and these differences in gene expression accurately distinguished cirrhotic from noncirrhotic alcoholics. Functionally related groups of genes were identified that are involved in cell adhesion, mitochondrial function, synaptic transmission, apoptosis, and cell proliferation. Both astrocytes and neuronal cells were affected at the transcriptional level. The regulated genes are involved in neurite growth, neuronal cell adhesion, synaptic vesicle release, and postsynaptic neurotransmission. Conclusions: These changes in the transcriptome likely contribute to the more severe brain dysfunction in cirrhotic alcoholics.

Maruyama K; Otsuki M. Incidence of alcoholic pancreatitis in Japanese alcoholics: Survey of male sobriety association members in Japan. Pancreas 34(1): 63-65, 2007. (14 refs.)

Objective: To estimate the incidence of alcoholic pancreatitis, a dependence questionnaire survey was administered to male members of the sobriety association in Japan. Methods: Questionnaires asking about age, age at start of alcohol drinking, amount of alcohol consumption, duration of drinking, the initiated age of abstinence, medical history of pancreatitis, the age at diagnosis of pancreatitis, and the etiology of pancreatitis were sent to 7876 male members of a sobriety association in Japan. Results: Of 4120 members who replied to the questionnaire, 857 (20.8%) had a medical history of pancreatitis. Of these 857 members, 418 (10.1%) had been diagnosed with alcoholic pancreatitis, 32 (0.8%) as gallstone pancreatitis, and 407 (9.9%) with unknown etiology or etiology forgotten. A clear history of pancreatitis and information on habitual heavy drinking and the consumed amount of alcohol could be obtained from 373 of the 418 members diagnosed with alcoholic pancreatitis and from 345 of the 407 members with pancreatitis of unknown etiology. These 718 respondents were considered to be true alcoholic pancreatitis cases, with an extrapolated incidence of 9.1% (718/7876) to 17.4% (718/4120) cases of alcoholic pancreatitis in alcoholics in Japan. Alcoholics with a history of pancreatitis began drinking at relatively younger age and consumed a significantly greater amount of alcohol per day compared with 3113 alcoholics without a medical history of pancreatitis. Conclusion: This survey suggests that the incidence of alcoholic pancreatitis in alcoholics is much higher than previously reported.

Maurage P; Campanella S; Philippot P; Martin S; de Timary P. Face processing in chronic alcoholism: A specific deficit for emotional features. Alcoholism: Clinical and Experimental Research 32(4): 600-606, 2008. (39 refs.)

Background: It is well established that chronic alcoholism is associated with a deficit in the decoding of emotional facial expression (EFE). Nevertheless, it is still unclear whether this deficit is specifically for emotions or due to a more general impairment in visual or facial processing. This study was designed to clarify this issue using multiple control tasks and the subtraction method. Methods: Eighteen patients suffering from chronic alcoholism and 18 matched healthy control subjects were asked to perform several tasks evaluating (1) Basic visuo-spatial and facial identity processing; (2) Simple reaction times; (3) Complex facial features identification (namely age, emotion, gender, and race). Accuracy and reaction times were recorded. Results: Alcoholic patients had a preserved performance for visuo-spatial and facial identity processing, but their performance was impaired for visuo-motor abilities and for the detection of complex facial aspects. More importantly, the subtraction method showed that alcoholism is associated with a specific EFE decoding deficit, still present when visuo-motor slowing down is controlled for. Conclusion: These results offer a post hoc confirmation of earlier data showing an EFE decoding deficit in alcoholism by strongly suggesting a specificity of this deficit for emotions. This may have implications for clinical situations, where emotional impairments are frequently observed among alcoholic subjects.

Maurage P; Campanella S; Philippot P; Pham TH; Joassin F. The crossmodal facilitation effect is disrupted in alcoholism: A study with emotional stimuli. Alcohol and Alcoholism 42(6): 552-559, 2007. (57 refs.)

Aims: Chronic alcoholism is classically associated with major deficits in the visual and auditory processing of emotions. However, the crossmodal (auditory-visual) processing of emotional stimuli, which occurs most frequently in everyday life, has not yet been explored. The aim of this study was to explore crossmodal processing in alcoholism, and specifically the auditory-visual facilitation effect. Methods: Twenty patients suffering from alcoholism, and 20 matched healthy controls had to detect the emotion (anger or happiness) displayed by auditory, visual or auditory-visual stimuli. The stimuli were designed to elicit a facilitation effect (namely, faster reaction times (RTs) for crossmodal condition than for unimodal ones). RTs and performance were recorded. Results: While the control subjects elicited a significant facilitation effect, alcoholic individuals did not present this effect, as no significant differences between RTs according to the modality were shown. This lack of facilitation effect is the marker of an impaired auditory-visual processing. Conclusions: Crossmodal processing of complex social stimuli (such as faces and voices) is crucial for interpersonal relations. This first evidence for a crossmodal deficit in alcoholism contribute in explaining the contrast observed between experimental results describing, up to now, mild impairments in emotional facial expression (EFE) recognition in alcoholic subjects (e.g. Oscar-Berman et al.,1990), and the many clinical observations suggesting massive problems.

Mechtcheriakov S; Brenneis C; Egger K; Koppelstaetter F; Schocke M; Marksteiner J. A widespread distinct pattern of cerebral atrophy in patients with alcohol addiction revealed by voxel-based morphometry. Journal of Neurology, Neurosurgery and Psychiatry 78(6): 610-614, 2007. (34 refs.)

Background: Patients with alcohol addiction show a number of transient or persistent neurological and psychiatric deficits. The complexity of these brain alterations suggests that several brain areas are involved, although the definition of the brain alteration patterns is not yet accomplished. Aim: To determine brain atrophy patterns in patients with alcohol dependence. Methods: Voxel-based morphometry (VBM) of grey matter (GM) and white matter (WM) was performed in 22 patients with alcohol dependence and in 22 healthy controls matched for age and sex. Results: In patients with alcohol dependence, VBM of GM revealed a significant decrease in density (p < 0.001) in the precentral gyrus, middle frontal gyrus, insular cortex, dorsal hippocampus, anterior thalamus and cerebellum compared with controls. Reduced density of WM was found in the periventricular area, pons and cerebellar pedunculi in patients with alcohol addiction. Conclusions: Our findings provide evidence that alcohol addiction is associated with altered density of GM and WM of specific brain regions. This supports the assumption that alcohol dependence is associated with both local GM dysfunction and altered brain connectivity. Also, VBM is an effective tool for in vivo investigation of cerebral atrophy in patients with alcohol addiction.

Mehlig K; Skoog I; Guo X; Schutze M; Gustafson D; Waern M et al. Alcoholic beverages and incidence of dementia: 34-year follow-up of the prospective population study of women in Goteborg. American Journal of Epidemiology 167(6): 684-691, 2008. (35 refs.)

The objective of this study was to assess the association between different types of alcoholic beverages and 34-year incidence of dementia. Among a random sample of 1,462 women aged 38-60 years and living in Goteborg, Sweden, in 1968-1969, 164 cases of dementia were diagnosed by 2002. At baseline as well as in 1974-1975, 1980-1981, and 1992-1993, the frequency of alcohol intake, as well as other lifestyle and health factors, was recorded and related to dementia with Cox proportional hazard regression, by use of both baseline and updated covariates. Wine was protective for dementia (hazard ratio (HR) = 0.6, 95% confidence interval (CI): 0.4, 0.8) in the updated model, and the association was strongest among women who consumed wine only (HR = 0.3, 95% CI: 0.1, 0.8). After stratification by smoking, the protective association of wine was stronger among smokers. In contrast, consumption of spirits at baseline was associated with slightly increased risk of dementia (HR = 1.5, 95% CI: 1.0, 2.2). Results show that wine and spirits displayed opposing associations with dementia. Because a protective effect was not seen for the other beverages, at least part of the association for wine may be explained by components other than ethanol.

Mendez-Sanchez N; Villa AR; Zamora-Valdes D; Morales-Espinosa D; Uribe M. Worldwide mortality from cirrhosis. Annals of Hepatology 6(3): 194-195, 2007. (5 refs.)

Background/Aims: Cirrhosis mortality has registered large changes over the last few decades. Aim: To report worldwide mortality due to cirrhosis over the period 1980-2002. Methods: Age-standardized (world standard) cirrhosis mortality rates per 100,000 were computed for 41 countries worldwide over the period 1980-2002 using data from WHO mortality database. Results: In the early 1980s, the highest rates were in Mexico, Chile (around 55/100,000 men and 14/100,000 women), France, Italy, Portugal, Austria, Hungary and Romania (around 30-35/100,000 men and 10-15/100,000 women). Mortality from cirrhosis has been steadily declining in most countries worldwide since the mid or late 1970s (annual percent change, APC, between -5 % and -1.5 % in the last decade only for both sexes). In southern Europe, rates in the early 2000s were less than halved compared to earlier decades. In contrast, rates have been rising in Eastern European countries to reach extremely high values in the mid 1990s, and declined only thereafter. In the UK rates were still steadily rising (APC around +7% in men and +3% in women from England and Wales, and +9% in men and +7% in women from Scotland). Conclusions: Mortality from cirrhosis shows favourable trends in most countries of the world, following the reduction in alcohol consumption and hepatitis B and C virus infection. The steady upward trends observed over more recent calendar periods in the UK and central and eastern European countries are attributed to the persistent increase in the prevalence of alcohol consumption.

Molina PE; Lang CH; McNurlan M; Bagby GJ; Nelson S. Chronic alcohol accentuates simian acquired immunodeficiency syndrome-associated wasting. Alcoholism: Clinical and Experimental Research 32(1): 138-147, 2008. (57 refs.)

Background: Survival following human immunodeficiency virus (HIV) infection has improved significantly following the advent of highly active antiretroviral therapy. A large percentage of HIV-infected patients consume and abuse alcohol. Erosion of lean body mass is an important contributing factor to patient morbidity and mortality, and is a common feature of both chronic alcohol (ALC) consumption and acquired immunodeficiency syndrome (AIDS). We hypothesized that alcohol-induced loss in lean body mass is likely to exacerbate the AIDS wasting syndrome, particularly at the terminal stage of AIDS (SAIDS). Methods: This study examined the impact of chronic, intra-gastric ALC (5 h/d x 4 d/wk; blood alcohol levels = 55 mM to 60 mM) administration on body composition and muscle mass in simian immunodeficiency virus (SIV)-infected male Rhesus macaques in contrast to SIV-infected isocaloric (22 kcal/kg/d) sucrose (SUC)-infused control animals at the terminal stage of SIV infection. Results: At terminal stage, ALC/SIV+ animals had significantly lower body weight, body mass index, and limb muscle area than SUC/SIV+ animals. Both ALC/SIV+ and SUC/SIV+ animals had suppressed expression of insulin-like growth factor-I and increased expression of the ubiquitin ligase muscle-specific RING finger-1 mRNA. ALC increased mRNA expression of atrogin-1 (pre-SIV and at SAIDS) and tumor necrosis factor (TNF)-alpha (SAIDS). These changes were not associated with significant differences in fractional rates of muscle protein synthesis or in overall survival rate. These data show that chronic ALC exacerbated the loss of muscle mass at terminal SAIDS. Conclusion: Our findings suggest the involvement of TNF-alpha and increased muscle proteolysis via atrogin-1 for the greater erosion of lean body mass at terminal SAIDS in ALC-treated Rhesus macaques.

Nazhel B; Arikan Z; Irkec C; Karakilic H. SSR abnormalities in chronic alcoholics. Addictive Behaviors 32(6): 1290-1294, 2007. (12 refs.)

We performed sympathetic skin response (SSR) studies on 29 male patients diagnosed as chronic alcoholics according to DSM-IV criteria. The average age was 43 years and the mean duration of alcohol abuse was 21 years, with all patients having a history of alcohol abuse for a minimum of 4 years. None of the patients had any symptoms and/nor signs related to autonomic nervous system dysfunction and all demonstrated normal nerve conduction velocities. Hand and foot latencies in alcoholics were prolonged relative to controls and the difference was statistically significant: reflected by p values of 0.02 and 0.004, respectively. Forty-four percent of patients demonstrated abnormal results. The unilateral prolongation of the lower extremity latency was the most commonly found abnormality (24%). Finding abnormal SSR in this patient population has made us aware that SSR has the potential to detect subclinical autonomic nervous system dysfunction even in patients who do not have autonomic complaints or neuropathy and to provide information about a part of the peripheral nervous system small unmyelinated C fibers that can not be assessed by currently performed techniques used in clinical EMG laboratories or by physical examination.

Nazliel B; Arikan Z; Irkec C. Visual evoked potentials in chronic alcoholism. Addictive Behaviors 32(7): 1470-1473, 2007. (11 refs.)

In order to evaluate the effect of alcohol consumption and the effect of abstinence on central nervous system generated parameters, we performed pattern visual evoked potential (PVEP) recordings on chronic alcoholics. The study was conducted on forty patients diagnosed as chronic alcoholics according to DSM IV criteria. They were aged mean: 42, and had histories of alcohol abuse for at least six years (mean: 21). 15% of the patients demonstrated abnormal VEP results at least in one tested eye. In order to test the effect of abstinence period on P100 latency values, alcoholics were divided in to two subgroups. Group I (Gr I) consisted twenty-four alcoholics who had been abstinent for less than thirty days (mean: 14), and Group II (Gr II) consisted sixteen alcoholics who had been abstinent for more than thirty and less than seventy-six days (mean: 38) The mean P100 latency of Gr I and Gr II was 101 and 102 milliseconds (ms) respectively; and when compared to normal controls the difference was statistically significant (p: 0.016, p: 0.009). Abnormal VEP in asymptomatic chronic alcoholics suggests that they may be useful in the detection of early changes and in following the progress of patients with the disorder.

Ness KJ; Fan J; Wilke WW; Coleman RA; Cook RT; Schlueter AJ. Chronic ethanol consumption decreases murine langerhans cell numbers and delays migration of langerhans cells as well as dermal dendritic cells. Alcoholism: Clinical and Experimental Research 32(4): 657-668, 2008. (42 refs.)

Background: Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration. Methods: Mice received 20% EtOH in the drinking water for up to 35 weeks. Baseline Langerhans cell (LC) and dermal DC (dDC) numbers were enumerated by immunofluorescence (IF). LC repopulation after inflammation was determined following congenic bone marrow (BM) transplant and ultraviolet (UV) irradiation. Net LC loss from epidermis was determined by IF following TNF-alpha or CpG stimulation. LC and dDC migration into LN was assessed by flow cytometry following epicutaneous FITC administration. Results: Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non-EtOH-exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH-fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application. Conclusions: Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect. These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration.

Noel X; Bechara A; Dan B; Hanak C; Verbanck P. Response inhibition deficit is involved in poor decision making under risk in nonamnesic individuals with alcoholism. Neuropsychology 21(6): 778-786, 2007. (52 refs.)

Individuals with alcoholism exhibit poor decision making as reflected by their continued alcohol use despite encountering problems and by low performance in laboratory tasks of decision making. Here, the authors investigated the relative contribution of several distinct processes of executive functions in performance on the Iowa Gambling Task (IGT; A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson. 1994) in recently detoxified individuals with alcoholism. Compared to matched healthy participants. individuals with alcoholism showed below-normal scores in the last 20 trials of the IGT as well as on other tasks of executive functions, specifically those assessing the capacity to manipulate information stored in working memory, detect abstract rules, or inhibit prepotent responses. Prepotent response inhibition best predicted performance in the late trials of the IGT, that is, when participants have likely acquired knowledge about the reward/punishment contingencies of the task. These results underline the important role that response inhibition plays in decision making, especially in risky situations, when knowledge of the probability of a given outcome becomes available (i.e. decisions under risk).

Noel X; Van der Linden M; d'Acremont M; Bechara A; Dan B; Hanak C et al. Alcohol cues increase cognitive impulsivity in individuals with alcoholism. Psychopharmacology 192(2): 291-298, 2007. (40 refs.)

Individuals with alcoholism are characterized by both attentional bias for alcohol cues and prepotent response inhibition deficit. We tested the hypothesis that alcoholics exhibit greater cognitive disinhibition when the response to be suppressed is associated with alcohol-related information. Forty recently detoxified individuals with alcoholism were compared with 40 healthy non-substance abusers on the "Alcohol-Shifting Task", a variant of the go/no-go paradigm requiring a motor response to targets and no response to distracters. The aim was to test the ability of alcoholics to discriminate between alcohol-related and neutral words. Sometimes, the alcohol-related words were the targets for the "go" response, with neutral words as distracters, sometimes the reverse. Several shifts in target type occurred during the task. Alcoholics made significantly more commission errors (i.e., press a key when a distracter displayed) and more omission errors (i.e., not press a key when a target displayed) than controls. Moreover, the number of commission errors was greater in alcoholics when alcohol-related stimuli had to be detected. These results demonstrate that alcoholics exhibit a basic prepotent response inhibition deficit, which is enhanced when the response to be suppressed is related to alcohol. We discuss clinical and theoretical implications of these findings.

O'Farrell A; Allwright S; Toomey D; Bedford D; Conlon K. Hospital admission for acute pancreatitis in the Irish population, 1997-2004: Could the increase be due to an increase in alcohol-related pancreatitis? Journal of Public Health 29(4): 398-404, 2007. (21 refs.)

To investigate trends in the incidence of acute pancreatitis by examining emergency admissions to acute public hospitals over an 8-year period; to compare trends for alcohol-related pancreatitis admissions with biliary tract-related admissions and to profile the patients admitted with an acute pancreatitis diagnosis. All in-patient emergency admissions for which an acute pancreatitis diagnosis (ICD-9-CM Code 577.0) was recorded as principal diagnosis were identified for years 1997-2004 inclusive. Alcohol-related acute pancreatitis admissions (i.e. had alcohol misuse recorded as co-morbidity) were identified using ICD-9-CM-codes 303 and 305. Biliary tract disease-related admissions (i.e. had biliary tract disease recorded as co-morbidity) were identified using ICD-9-CM codes 574.0-576.0 inclusive. Pearson's chi(2)-test was used to compare proportions in groups of categorical data and chi(2)-tests for trend were used to identify linear trends. There were 6291 emergency admissions with a principal diagnosis of acute pancreatitis during the 8 year study period, with 622 admissions in 1997 compared to 959 admissions in 2004, an increase of 54.1%. Age standardized rates rose significantly from 17.5 per 100 000 population in 1997 to 23.6 per 100 000 in 2004, (P < 0.01 for linear trend). There were 1205 admissions with alcohol misuse recorded as a co-morbidity increasing from 13.9% (87/622) of acute pancreatitis admissions in 1997 to 23.2% (223/959) in 2004. This increase was significantly greater than the increase observed for biliary tract disease-related admissions, 19.6% (122/622) in 1997 to 23.5% (225/959) in 2004. Rates for total acute pancreatitis admissions were highest in those aged 70 years and over; the majority (3563, 56.6%) of the admissions were male with a mean age of 51.1 years (SD 19.9); the mean age for male admissions was significantly younger than for female admissions (49.1 versus 53.6 years, P < 0.001). However, for alcohol-related admissions, rates were highest in those aged 30-49 years and patients admitted with alcohol misuse recorded were significantly younger than those who did not have alcohol misuse recorded (42.0 versus 53.2 years, P < 0.001). Median length of stay was 7 days. Hospital admissions for acute pancreatitis rose from 17.5 per 100 000 population in 1997 to 23.6 per 100 000 in 2004. The proportion of admissions that had alcohol misuse recorded as a co-morbidity rose more markedly than those with biliary tract disease and the rise was more pronounced in younger age groups. The increasing trend in alcohol-related acute pancreatitis parallels the rise in per capita alcohol consumption. Given the continuing rise in binge drinking, particularly among young people, this is a cause for concern.

Oscar-Berman M; Marinkovic K. Alcohol: Effects on neurobehavioral functions and the brain. (review). Neuropsychology Review 17(3): 239-257, 2007. (244 refs.)

Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction.

Otis JS; Mitchell PO; Kershaw CD; Joshi PC; Guidot DM. Na,K-ATPase expression is increased in the lungs of alcohol-fed rats. Alcoholism: Clinical and Experimental Research 32(4): 699-705, 2008. (42 refs.)

Background: Alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome (ARDS), a disease characterized by diffuse alveolar epithelial damage, lung edema, and consequent severe hypoxemia. Chronic alcohol abuse increases alveolar epithelial permeability both in vitro and in vivo, in part due to altered tight junction formation. However, both alcohol-fed animals and otherwise healthy alcoholic humans do not have pulmonary edema at baseline, even though their lungs are highly susceptible to acute edematous injury in response to inflammatory stresses. This suggests that active fluid transport by the alveolar epithelium is preserved or even augmented in the alcoholic lung. Chronic alcohol ingestion increases expression of apical sodium channels in the alveolar epithelium; however, its effects on the Na,K-ATPase complex that drives sodium and fluid transport out of the alveolar space have not been examined. Methods: Age- and gender-matched Sprague-Dawley rats were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 6 weeks. Gene and protein expression of lung Na,K-ATPase alpha 1, alpha 2, and beta 1 subunits were quantified via real-time PCR and immunobiological analyses, respectively. Alcohol-induced, Na,K-ATPase-dependent epithelial barrier dysfunction was determined by calculating lung tissue wet:dry ratios following an ex vivo buffer-perfused challenge for 2 hours in the presence of ouabain (10(-4) M), a Na,K-ATPase inhibitor. Results: Chronic alcohol ingestion significantly increased gene and protein expression of each Na,K-ATPase subunit in rat lungs. Immunohistochemical analyses of the alcoholic lung also revealed that protein expression of the Na,K-ATPase alpha 1 subunit was increased throughout the alveolar epithelium. Additionally, lungs isolated from alcohol-fed rats developed more edema than comparably treated lungs from control-fed rats, as reflected by increased lung tissue wet:dry ratios. Conclusions: These findings indicate that chronic alcohol ingestion, which is known to increase alveolar epithelial paracellular permeability, actually increases the expression of Na,K-ATPase in the lung as a compensatory mechanism. This provides a potential explanation as to why the otherwise healthy alcoholic does not have evidence of pulmonary edema at baseline.

Pitel AL; Beaunieux H; Witkowski T; Vabret F; Guillery-Girard B; Quinette P et al. Genuine episodic memory deficits and executive dysfunctions in alcoholic subjects early in abstinence. Alcoholism: Clinical and Experimental Research 31(7): 1169-1178, 2007. (78 refs.)

Background: Chronic alcoholism is known to impair episodic memory function, but the specific nature of this impairment is still unclear. Moreover, it has never been established whether episodic memory deficit in alcoholism is an intrinsic memory deficit or whether it has an executive origin. Thus, the objectives are to specify which episodic memory processes are impaired early in abstinence from alcohol and to determine whether they should be regarded as genuine memory deficits or rather as the indirect consequences of executive impairments. Methods: Forty recently detoxified alcoholic inpatients at alcohol entry treatment and 55 group-matched controls underwent a neuropsychological assessment of episodic memory and executive functions. The episodic memory evaluation consisted of 3 tasks complementing each other designed to measure the different episodic memory components (learning, storage, encoding and retrieval, contextual memory, and autonoetic consciousness) and 5 executive tasks testing capacities of organization, inhibition, flexibility, updating, and integration. Results: Compared with control subjects, alcoholic patients presented impaired learning abilities, encoding processes, retrieval processes, contextual memory and autonoetic consciousness. However, there was no difference between the 2 groups regarding the storage capacities assessed by the rate of forgetting. Concerning executive functions, alcoholic subjects displayed deficits in each executive task used. Nevertheless, stepwise regression analyses showed that only performances on fluency tasks were significantly predictive of some of the episodic memory disorders (learning abilities for 40%, encoding processes for 20%, temporal memory for 21%, and state of consciousness associated with memories for 26%) in the alcoholic group. Discussion: At alcohol treatment entry, alcoholic patients present genuine episodic memory deficits that cannot be regarded solely as the consequences of executive dysfunctions. These results are in accordance with neuroimaging findings showing hippocampal atrophy. Moreover, given the involvement of episodic memory and executive functions in alcohol treatment, these data could have clinical implications.

Poikolainen K; Alho H. Magnesium treatment in alcoholics: A randomized clinical trial. Substance Abuse Treatment, Prevention, and Policy 3(e-article 2), 2008. (17 refs.)

Background: Magnesium (Mg) deficiency is common among alcoholics. Earlier research suggests that Mg treatment may help to normalize elevated enzyme activities and some other clinically relevant parameters among alcoholics but the evidence is weak. Methods: The effect of Mg was studied in a randomized, parallel group, double blind trial. The patients were first treated for alcohol withdrawal symptoms and then received for 8 weeks either 500 mg of Mg divided into two tablets or matching placebo. Measurements were made at the beginning and in the end of the Mg treatment period. The primary outcome was serum gamma-glutamyltransferase (S-GGT) activity; secondary outcomes included aspartate-aminotransferase (S-AST) and alanine-aminotransferase (S-ALT) activity. Results:The number of randomized patients (completers) was 64 (27) in the treatment and 54 (31) in the control group. In intention-to-treat-analyses and in most analyses of study completers, there were no significant differences between the Mg-treated and placebo groups in the outcome variables. When baseline serum Mg level, coffee intake, and the number of unused Mg tablets were controlled for in a multivariate regression model, after-treatment serum Mg levels were found to be higher among the Mg-treated group than in the placebo group (t-test 3.334, df=53, p=0.002). After controlling for age, body weight, baseline alcohol intake, subsequent change in alcohol intake and baseline S-AST, the after-treatment S-AST levels were found to be lower among the Mg-treated group than in the placebo group (t-test 2.061, df=49, p=0.045). Conclusions: Mg treatment may speed up the S-AST decrease in compliant patients. This might decrease the risk of death from alcoholic liver disease. Correction. After publication of our work (Poikolainen et al; Substance Abuse Treatment, Prevention, and Policy 2008, 3:1), we noticed that the magnesium (Mg) content of the trial tablets was inadvertently given as 250 mg. The correct content was 200 mg. Thus the first sentence under the subtitle "Intervention" should read: The patients received orally for 8 weeks either a daily dose of 400 mg of Mg tablets divided in two tablets (200 mg each) or matching placebo tablets.

Polikandriotis JA; Rupnow HL; Brown LA; Hart CM. Chronic ethanol ingestion increases nitric oxide production in the lung. Alcohol 41(5): 309-316, 2007. (25 refs.)

Chronic ethanol (EtOH) ingestion increases the incidence of acute respiratory distress syndrome. The mechanisms underlying EtOH-induced susceptibility to lung injury continue to be defined. This study examines the hypothesis that EtOH increases endothelial nitric oxide synthase (eNOS) expression and activity in the lungs of a rat model of chronic EtOH ingestion. Male Sprague-Dawley rats were fed liquid diets containing EtOH (36% of calories) or maltose-dextrin as an isocaloric substitution for EtOH (control) for 6 weeks. Selected animals were also treated with the angiotensin-converting enzyme (ACE) inhibitor lisinopril (3 mg/l in diet) for 6 weeks. At study completion, animals were sacrificed, and lung tissue was collected for assays of nitric oxide (NO) metabolism or pulmonary microvascular endothelial cells (MVEC) were isolated for analysis of NO release. Compared to the control diet, chronic EtOH ingestion increased lung H2O2 production, eNOS expression and activity, lung cyclic guanosine monophosphate (cGMP) content, and levels of protein nitration and oxidation. MVEC from animals with chronic EtOH ingestion released greater amounts of NO. EtOH-induced increases in lung H2O2 production, eNOS expression and activity, cGMP content, protein nitration and oxidation, and MVEC NO production were all attenuated by treatment with lisinopril. Chronic EtOH ingestion stimulates ACE-dependent increases in NO production in the lung. These novel findings indicate that chronic EtOH ingestion increases reactive species production in the lung parenchyma and provide new insights into mechanisms by which EtOH causes phenotypic alterations in the lung and alters the lung's response to inflammatory stimuli.

Rehm J; Taylor B; Roerecke M; Patra J. Alcohol consumption and alcohol-attributable burden of disease in Switzerland, 2002. International Journal of Public Health 52(6): 383-392, 2007. (47 refs.)

Objectives: This analysis estimated alcohol-attributable burden of disease for Switzerland. Methods: Exposure distributions were taken from the 2002 Swiss Health Survey and adjusted for per capita consumption. Risk relations were taken from meta-analyses. Mortality and burden of disease data were taken from the World Health Organization. Results: Overall consumption and alcohol-attributable mortality and burden of disease in Switzerland were high compared to European and global averages, especially among women. Overall in Switzerland in 2002, 2016 deaths (5.2% of all deaths in men, 1.4% in women), 28,939 years of life lost (men: 10.5%, women: 4.9%) and 70,256 disability adjusted life years (men: 12.9%, women: 4.2%) were attributable to alcohol. These numbers are net numbers already incorporating the cardio-protective and other beneficial effects of alcohol. Conclusions: Limitations of the approach used are discussed. In addition, questions of causality and confounding are addressed.

Retana-Ugalde R; Altamirano-Lozano M; Mendoza-Nunez VM. Is there a similarity between DNA damage in adults with chronic alcoholism and community-dwelling healthy older adults? Alcohol and Alcoholism 42(2): 64-69, 2007. (48 refs.)

Aims: Daily alcohol consumption and ageing have been linked with DNA damage, leading to the hypothesis that chronic alcoholism causes DNA damage similar to that which occurs with ageing. Likewise, it has been suggested that chronic alcoholism is the cause of accelerated or premature ageing. The objective of this study was to evaluate the frequency and magnitude of DNA damage among adults with chronic alcoholism and healthy older adults residing in Mexico City. Methods: A cross-sectional and comparative study was carried out in a sample of 53 chronic alcoholics of 25-44 years of age (without alcohol ingestion in the past 30 days) without additional diseases, 26 healthy subjects >= 60 years of age, and 25 healthy adults of 25-44 years of age without alcohol addiction, all residents of Mexico City during the past 10 years. DNA damage was evaluated by single-cell gel electrophoresis technique (Comet assay). Results: Our results showed a similar percentage of DNA damage between healthy elderly subjects and chronic alcoholics (62 vs 55%, P > 0.05), although average DNA migration was greater in alcoholics than in the elderly (78.1 33.2 vs 58.6 26.2, P = 0.09). However, the percentage of subjects with more than six damaged cells was higher in the older adults subjects group than in the group chronic alcoholics (19 vs 35%, P = 0.16). Conclusions: Data suggest that DNA damage is not similar in young subjects with chronic alcoholism that which occurs with ageing.

Sechi G; Serra A. Wernicke's encephalopathy: New clinical settings and recent advances in diagnosis and management. (review). Lancet Neurology 6(5): 442-455, 2007. (166 refs.)

Wernicke's encephalopathy is an acute neuropsychiatric syndrome resulting from thiamine deficiency, which is associated with significant morbidity and mortality. According to autopsy-based studies, the disorder is still greatly underdiagnosed in both adults and children. In this review, we provide an update on the factors and clinical settings that predispose to Wernicke's encephalopathy, and discuss the most recent insights into epidemiology, pathophysiology, genetics, diagnosis, and treatment. To facilitate the diagnosis, we classify the common and rare symptoms at presentation and the late-stage symptoms. We emphasise the optimum dose of parenteral thiamine required for prophylaxis and treatment of Wernicke's encephalopathy and prevention of Korsakoffs syndrome associated with alcohol misuse. A systematic approach helps to ensure that patients receive a prompt diagnosis and adequate treatment.

Seitz HK; Stickel F. Alcoholic liver disease in the elderly. Clinics in Geriatric Medicine 23(4): 905-+, 2007. (83 refs.)

Although per capita alcohol consumption, and thus the prevalence of alcoholic liver disease, decreases generally with age in Europe and in the United States, recently an increase in alcohol consumption has been reported in individuals over 65 years. Reasons explaining this observation may include an increase in life expectancy or a loss of life partners and, thus, loneliness and depression. Although ethanol metabolism and ethanol distribution change with age, and an elderly person's liver is more susceptible to the toxic effect of ethanol, the spectrum of alcoholic liver diseases and their symptoms and signs is similar to that seen in patients of all ages. However, prognosis of alcoholic liver disease in the elderly is poor. In addition, chronic alcohol consumption may enhance drug associated liver disease and may also act as a cofactor in other liver diseases, such as viral hepatitis and nonalcoholic fatty liver disease.

Sisson JH. Alcohol and airways function in health and disease. (review). Alcohol 41(5): 293-307, 2007. (101 refs.)

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The effect of alcohol on lung airway functions is dependent on the concentration, duration, and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation, and probably attenuates the airway inflammation and injury observed in asthma and chronic obstructive pulmonary disease (COPD). Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management, and likely worsens outcomes including lung function and mortality in COPD patients. Nonalcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase 2. The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation, and the interaction with other airway exposure agents, such as cigarette smoke, represents opportunities for future investigation.

Solfrizzi V; D'Introno A; Colacicco AM; Capurso C; Del Parigi A; Baldassarre G; Italian Longitudinal Study Aging W. Alcohol consumption, mild cognitive impairment, and progression to dementia. Neurology 68(21): 1790-1799, 2007. (44 refs.)

Objective: To estimate the impact of alcohol consumption on the incidence of mild cognitive impairment and its progression to dementia. Methods: We evaluated the incidence of mild cognitive impairment in 1,445 non-cognitively impaired individuals and its progression to dementia in 121 patients with mild cognitive impairment, aged 65 to 84 years, participating in the Italian Longitudinal Study on Aging, with a 3.5-year follow-up. The level of alcohol consumption was ascertained in the year before the survey. Dementia and mild cognitive impairment were classified using current clinical criteria. Results: Patients with mild cognitive impairment who were moderate drinkers, i.e., those who consumed less than 1 drink/day (approximately 15 g of alcohol), had a lower rate of progression to dementia than abstainers (hazard ratio [HR] 0.15; 95% CI 0.03 to 0.78). Furthermore, moderate drinkers with mild cognitive impairment who consumed less than 1 drink/ day of wine showed a significantly lower rate of progression to dementia than abstainers (HR 0.15; 95% CI 0.03 to 0.77). Finally, there was no significant association between higher levels of drinking (>= 1 drink /day) and rate of progression to dementia in patients with mild cognitive impairment vs abstainers. No significant associations were found between any levels of drinking and the incidence of mild cognitive impairment in non-cognitively impaired individuals vs abstainers. Conclusions: In patients with mild cognitive impairment, up to 1 drink/day of alcohol or wine may decrease the rate of progression to dementia.

Stevens A; Peschk I; Schwarz J. Implicit learning, executive function and hedonic activity in chronic polydrug abusers, currently abstinent polydrug abusers and controls. Addiction 102(6): 937-946, 2007. (47 refs.)

Aims: The study seeks to evaluate impairments of implicit learning and executive function in chronic polydrug abusers. It was hypothesized that implicit learning and executive function correlate with anhedonia. Design A cross-sectional group comparison. Settings: Department of Psychiatry, University of Tubingen, Germany. Participants: A total of 25 male polydrug abusers with opiate dependence, n = 26 polydrug abusers abstinent for more than 3 months and n = 26 non-drug-using healthy males. Setting Abstinent polydrug abusers were recruited from a community treatment centre, current polydrug abusers from local drug counselling services and controls through advertisements. Measurements: A psychological battery assessing implicit learning (serial reaction-time task), various executive functions (latent inhibition, delayed matching-to-sample, Trail Making Test, acquisition and modification of conditioned responses, figural reasoning) and verbal logic memory was administered. Hedonic thoughts and activities as well as depressive symptoms were assessed through questionnaires. Findings In chronic polydrug abusers, there were moderate impairments of implicit learning, of acquisition, reversal and extinction of conditioned responses, of latent inhibition as well as anhedonia, while working memory was spared. In the abstinent group, cognitive performance was normal except for latent inhibition and more anhedonia and depression than in controls. Conclusions: The findings suggest that current polydrug abusers suffer from impairment of many cognitive functions and from anhedonia. During abstinence, there is near normal cognitive function but still anhedonia. Anhedonia was correlated with implicit learning but not with executive function.

Szabo G; Mandrekar P; Oak S; Mayerle J. Effect of ethanol on inflammatory responses: Implications for pancreatitis. (review). Pancreatology 7(2/3): 115-123, 2007. (45 refs.)

Background/Aims: Alcohol use alters inflammatory cell responses. While alcohol has direct effects on pancreatic acinar cells, activation of inflammatory cells is a major component of the pathology of alcoholic pancreatitis. Methods: The effects of acute or chronic alcohol exposure were evaluated in human monocytes on the production of TNF alpha or IL10 production, pro-inflammatory gene and nuclear factor-kappa B (NF-kappa B) activation. Results: Moderate, acute alcohol consumption or equivalent doses of alcohol in vitro had anti-inflammatory effects on monocyte activation via inhibition of pro-inflammatory genes and NF-kappa B activation, inhibition of TNF alpha production and augmentation of the anti-inflammatory cytokine, IL-10. In contrast, acute alcohol treatment augmented NF-kappa B activation and TNF alpha production and inhibited IL-10 levels in the presence of complex stimulation with combined TLR2 and TLR4 ligands. Prolonged alcohol exposure also resulted in an increase in NF-kappa B and TNF alpha production in response to TLR4 stimulation with LPS. Conclusion: These results suggest that alcohol can either attenuate or promote inflammatory responses that are critical in pancreatitis. Our results support the hypothesis that both acute alcohol intake in the presence of complex stimuli (such as necrotic cells) and chronic alcohol exposure result in hyper-responsiveness of monocytes to inflammatory signals and may contribute to increased inflammation in pancreatitis.

Thomson AD; Cook CCH; Guerrini I; Sheedy D; Harper C; Marshall EJ. Wernickes encephalopathy: 'Plus ca change, plus c'est la meme chose'. Alcohol and Alcoholism 43(2): 180-186, 2008. (40 refs.)

Aims: To develop clinical guidelines to identify individuals who misuse alcohol and are at risk of developing Wernickes Encephalopathy (WE). Method: Non-systematic literature review of studies which includes a careful clinical record of the development of signs and symptoms of thiamine deficiency and in which the diagnosis of WE has been confirmed at autopsy. Results: The review of the clinical findings in cases of WE, diagnosed at autopsy, shows a consistent pattern of signs and symptoms. The pattern appears to be similar regardless of whether the thiamine deficiency is related to nutritional problems alone or associated with alcohol misuse. Conclusions: The assessment of the degree of thiamine deficiency and the diagnosis of WE remain a clinical evaluation, and guidelines are suggested to help the clinician. Since neurotoxicity due to the metabolism of excessive alcohol in patients with chronic and severe alcohol dependence may be an important factor in determining long-term outcome of treatment, this must form part of the overall evaluation.

Thomson AD; Cook CCH; Guerrini I; Sheedy D; Harper C; Marshall EJ. Wernicke's encephalopathy revisited. (review). Alcohol and Alcoholism 43(2): 174-179, 2008. (16 refs.)

Aims: A translation into English of the case history section of Carl Wernickes original manuscript of 1881, with a discussion on its relevance for clinicians today. Methods: A copy of Carl Wernickes original German text was obtained by one of the authors (CCHC) and translated into English from the old German by a professional translator. Results: The translation was subsequently agreed by native German speaking referees, and minor changes made. Conclusions: The authors studied the translation in detail and concluded that Wernickes description had stood the test of time. The diagnosis of Wernickes Encephalopathy remains a clinical one.

Underwood MD; Mann JJ; Huang YY; Arango V. Family history of alcoholism is associated with lower 5-HT2A receptor binding in the prefrontal cortex. Alcoholism: Clinical and Experimental Research 32(4): 593-599, 2008. (51 refs.)

Background: 5-Hydroxytryptophan (5-HT2A) receptor involvement in alcoholism is suggested by less 5-HT2A binding in alcohol preferring rats, association of a 5-HT2A receptor gene polymorphism with alcohol dependence and reduced alcohol intake with 5-HT2A antagonists. We sought to determine postmortem whether 5-HT2A receptors are altered in the prefrontal cortex (PFC) of alcoholics. Methods: Brain tissue from 25 alcoholics and 19 controls was collected at autopsy. Diagnosis of DSM-IV alcoholism/abuse and other psychiatric disorders and the determination of family history of alcoholism were made by psychological autopsy. Specific binding to 5-HT2A (H-3-ketanserin) receptors in the PFC was measured by quantitative autoradiography. Results: 5-HT2A binding decreased with age [Brodmann areas (BA) 9, 46 gyrus; r = -0.381, -0.334, p < 0.05]. No differences in receptor binding between alcoholics and controls were detected in the gyrus or sulcus of any PFC area examined. Cases (controls or alcoholics) with a family history of alcoholism (n = 23) had less 5-HT2A binding throughout PFC than subjects without (n = 21) a family history of alcoholism (p < 0.05). 5-HT2A receptor binding in alcoholics without a family history of alcoholism (n = 7) did not differ from controls without a family history of alcoholism (n = 14). There was no association between alcoholism or alcohol rating and genotype. There was an association between genotype and the total amount of H-3-ketanserin binding in BA46 with the TT genotype having more binding (TT > TC approximate to CC). Conclusions: Lower 5-HT2A receptor binding in the PFC of cases with a family history of alcoholism suggests a genetic predisposition to alcoholism. Alcohol abuse by itself did not have a significant effect on PFC 5-HT2A binding and as 5-HT2A binding in alcoholics is not different from controls and antagonists may be therapeutic, fewer receptors may result in downstream developmental effects on the brain resulting in a predisposition to alcoholism.

Vargas R; Lang CH. Alcohol accelerates loss of muscle and impairs recovery of muscle mass resulting from disuse atrophy. Alcoholism: Clinical and Experimental Research 32(1): 128-137, 2008. (52 refs.)

Background: Muscle disuse atrophy is observed in patients recovering from trauma and there is an increased risk and severity of injury in patients abusing alcohol (EtOH). However, the interaction of EtOH and disuse on muscle protein balance has not been examined. Therefore, the present study addressed the hypothesis that EtOH accelerates the disuse atrophy and/or impairs the accretion of muscle protein durin