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[Anxiety in alcohol-dependent patients].

Alcoholism and anxiety disorders are concomitant far more frequently than might be expected. The great prevalence of anxiety disorders in alcoholics constitutes an important clinical issue because alcoholic subjects with a coexisting anxiety disorder suffer more frequent and more severe relapses than nonalcoholic control subjects. The former also how greater liability to psychotropic drug abuse and overdose behaviour, and are at greater risk of suicide. The type of relationship between alcohol dependence and anxiety disorders has considerable theoretical meaning. Four possible non-mutually exclusive ways of association are discussed: 1. the ingestion of alcohol may be an attempt at self-medication of anxiety symptoms; 2. anxiety and alcohol abuse may, independent of each other, be based on a third underlying, possibly genetic, factor; 3. anxiety may be a toxic effect of alcohol abuse or of withdrawal; 4. anxiety may result from cognitive processes in connection with alcohol abuse or withdrawal. Clinical guidelines for the pharmacotherapy of anxiety in patients suffering from alcoholism are outlined.

Alcoholism↗

Severity of alcohol dependence in patients with alcoholic liver disease.

To determine the severity of dependence on alcohol in patients with alcoholic liver disease the severity of alcohol dependence questionnaire was administered to 193 patients with various types of alcoholic liver disease established histologically, in whom a detailed history of lifetime alcohol consumption was also obtained. Only 34 patients (18%) were classified as being severely dependent compared with 56% of patients without overt liver disease who were attending a neighbouring alcohol treatment unit. There was a significant correlation between the severity of dependence and mean daily alcohol consumption (r = 0.45 and 0.39 for men and women, respectively) but not duration of drinking. Dependence scores tended to be lower in patients with cirrhosis than in those with precirrhotic liver disease, but this difference reached significance only in women. These findings confirm that patients who develop chronic alcoholic liver disease are usually only mildly dependent on alcohol and support the hypothesis that patients who escape florid symptoms of alcohol dependence are at greater risk of developing liver damage because they are able to sustain a continual consumption of alcohol over many years.

Adult↗

A survey estimate of academic liver transplant teams' selection practices for alcohol-dependent applicants.

Alcoholism itself is not a contraindication to liver transplantation. However, certain individual alcoholic applicants may pose an unacceptably high psychosocial risk of poor outcome. Transplant psychiatrists or psychologists at 14 academic liver transplant centers were asked to estimate their centers' selection practices with regard to specific problems in the more difficult alcohol-dependent applicant and with regard to hypothetical problem cases. There was impressive variability in estimated selection practice between the centers. However, the centers consistently appeared to prefer to require rehabilitation or observation in difficult situations rather than to reject applicants outright. The results provide an initial estimate of current thinking and practice with regard to the more difficult alcoholic applicant and suggest directions for further study.

Adult↗

Concomitant endocrine and immune alterations during alcohol intoxication and acute withdrawal in alcohol-dependent subjects.

Although both alcohol intoxication and withdrawal have been demonstrated to produce significant endocrine alterations, no data exist on the effects of acute withdrawal on immune functions. Therefore, the current study investigated the effect of alcohol intoxication and acute withdrawal on plasma cortisol, prolactin and catecholamines, and blood leukocyte subset distribution in alcohol-dependent subjects. Nine male alcoholics admitted to the university clinic for alcohol dependence and 9 age-matched controls participated in the study. Blood was drawn from the alcohol-dependent subjects at 10:30 a.m. on day 0 (chronic alcohol intoxication), at the same time during acute alcohol withdrawal (day 1) and following the resolution of acute withdrawal (day 7). Blood was drawn from age- and gender-matched healthy control subjects at the corresponding time points. Plasma was then analyzed for hormone concentrations and blood examined for leukocyte subsets by flow cytometry. Alcohol-dependent patients displayed significantly elevated plasma cortisol during intoxication and withdrawal, which decreased to control levels following resolution of acute withdrawal. Small elevations of plasma prolactin and catecholamines were also observed during intoxication. Furthermore, alcohol-dependent subjects showed reduced absolute numbers of CD4(+) and CD8(+) T cells and natural killer cells compared with healthy controls across all time points. In contrast, although monocyte numbers were lower in alcohol-dependent patients during intoxication, acute alcohol withdrawal increased the number of monocytes in patients. Thus, alcohol dependence produces a general suppression of leukocyte subset populations in blood. However, resolution of acute alcohol withdrawal is associated with a return of plasma cortisol to control levels, and a concomitant increase in peripheral blood monocyte numbers.

Alcoholic Intoxication↗

Alcohol dependence and simultaneous cocaine and alcohol use in cocaine-dependent patients.

Alcohol use and associated factors were studied in 124 consecutive cocaine-dependent admissions to an outpatient substance abuse clinic. Two analyses were conducted: First, those who did and did not meet criteria for current alcohol dependence were compared on sociodemographic and drug use characteristics. Second, patients who reported simultaneous cocaine and alcohol use on > 50% vs. < or = 50% of the occasions that they used cocaine were compared using the same dependent measures. Fifty-seven percent of patients met criteria for current alcohol dependence. Those with and without alcohol dependence did not differ on any sociodemographic characteristics, but those with dependence scored higher on the alcohol and family subscales of the Addiction Severity Index, the Michigan Alcoholism Screening Test, and measures of alcohol use, and were more likely to use cocaine and alcohol simultaneously, to use cocaine with friends and in social settings, and were more likely to report financial difficulties and unwanted sexual relations as adverse consequences of their cocaine use. Sixty-four percent of patients reported > 50% simultaneous cocaine and alcohol use. The two groups did not differ on any sociodemographic characteristics, but those reporting greater simultaneous use were more likely to be alcoholic, scored higher on most measures of alcohol use, and were more likely to report using cocaine with friends and in social settings. The only other differences observed between the two groups were fewer reports of seizures or difficulty concentrating in the group reporting greater simultaneous use. The present results confirm prior reports on the widespread prevalence of alcohol dependence among cocaine-dependent patients and extend them by providing new information on the prevalence and other characteristics of simultaneous cocaine and alcohol use.

Adult↗

The impact of a family history of alcoholism on the relationship between age at onset of alcohol use and DSM-IV alcohol dependence: results from the National Longitudinal Alcohol Epidemiologic Survey.

Both the age at onset of alcohol use and a family history of alcoholism can influence a person's risk of becoming alcohol dependent. The relationship between lifetime alcohol dependence, age at first alcohol use, and a family history of alcoholism was investigated using data obtained in the 1992 National Longitudinal Alcohol Epidemiologic Survey. This analysis demonstrated that regardless of the family history of alcoholism, respondents with an earlier age of drinking onset were more likely to become alcohol dependent compared with respondents with a later age of drinking onset. Among all age, race, and gender subgroups studied, however, people with a family history of alcoholism had a higher prevalence of lifetime alcohol dependence than did people without such a history.

Age of Onset↗

Alterations of neocortical neuronal responses to acetylcholine and GABA in rats born to alcohol-dependent mothers.

Alcohol is known to be a CNS teratogenic factor interfering with neuronal and synaptic maturation. The purpose of this microiontophoretic study was to explore GABAergic and cholinergic central mechanisms in adult rats exposed to alcohol in the third phase of prenatal life (ADM), when their mothers were subjected to alcohol physical dependence induction (9.6 g/kg/day). Responses to acetylcholine and GABA were recorded in frontal and somatosensory cortical neurons. Adult rats, whose mothers had been administered placebo with identical procedures, were used as a control (C). Cholinergic responses were significantly decreased and GABAergic responses increased in ADM animals with respect to controls. After a single i.p. alcohol injection (1.6 g/kg) spontaneous firing was depressed in ADM animals to a lesser extent than in C rats. Cholinergic excitations were reduced in C group and potentiated with reversal of atropine antagonism in ADM animals. GABAergic inhibitions were slightly increased and bicuculline antagonism was blocked in C rats, while ADM animals showed decreased responses to GABA. The present results support the hyperactivity of GABAergic system and the hypoactivity of cholinergic system reported in previous studies on prenatally and postnatally alcohol-exposed animals. Microiontophoretic results following ethanol injection led to the hypothesis that a rapid tolerance/dependence may develop in the offspring of alcohol-dependent rats.

Acetylcholine↗

Alcohol dependence is associated with the ZNF699 gene, a human locus related to Drosophila hangover, in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) sample.

Because tolerance is an important aspect of alcohol dependence (AD) in humans, recent evidence showing that the Drosophila gene hang is critically involved in the development of alcohol tolerance in the fly suggests that variation in related human loci might be important in the etiology of alcohol-related disorders. The orthology of hang in mammals is complex, but a number of human gene products (including ZNF699) with similar levels of amino-acid identity (18-26%) and similarity (30-41%), are consistently identified as the best matches with the translated hang sequence. We tested for association between the dichotomous clinical phenotype of alcohol dependence and seven single nucleotide polymorphisms (SNPs) in ZNF699 in our sample of 565 genetically independent cases and 496 siblings diagnosed with AD, and 609 controls. In analyses of genetically independent cases and controls, four of the seven single markers show strong evidence for association with AD (0.00003<Fisher's exact P<0.001), and the most significant single marker, rs7254880, tags an associated haplotype with frequency 0.071 in cases compared to 0.034 in controls (chi2 15.563, P<0.00008, 5000 permutation P<0.001, OR 2.17); inclusion of affected siblings gives similar results. Expression analyses conducted in independent postmortem brain samples show that expression of ZNF699 mRNA is significantly reduced in the dorsolateral prefrontal cortex of individuals carrying this haplotype compared with other observed haplotype combinations.

Alcohol-Related Disorders↗

Old wine, new bottle. The alcohol dependence syndrome.

The alcohol dependence syndrome is at once a fresh approach and a restatement of established clinical lore. It is, perhaps, old wine in a new bottle. Nonetheless, behavioral researchers in this field have needed some clinically sound criteria to differentiate between subjects to account for the variability of behavioral and psychophysiologic responses to alcohol in the laboratory. Cross-cultural researchers, and those interested in the genetics of alcoholism, have needed culture-free criteria for the diagnosis of alcoholism that might help them to separate aspects of the disorder that are genetically determined from those that are influenced by culture, immediate environment, and psychopathology. The beauty of the alcohol-dependence syndrome construct is its apparent specificity and its potential clinical usefulness. The difficulty with the concept is that no questionnaire has proven entirely satisfactory in defining the severity of alcohol dependence nor have biologic variables been identified that can provide valid and reliable indicators of severity. Nonetheless, advances in biomedical research frequently await the development of a nomenclature that will permit replicable scientific investigation. The evolving definition of the alcohol dependence syndrome is consistent with this tradition.

Alcoholism↗

Standard calculation of ethanol elimination rate is not sufficient to provide ethanol substitution therapy in the postoperative course of alcohol-dependent patients.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a severe complication during postoperative treatment of alcohol-dependent patients. Besides the use of clomethiazole, clonidine, and benzodiazepines, there is another possible way to prevent AWS by deliberate administration of ethanol. The appropriate dosage of ethanol has not been known up to now and it could be defined according to the average ethanol elimination rate (EER) which, from forensic analysis, is known to be 15 mg/dl per h in a normal population. However, it is questionable whether these data are suitable for the calculation of the correct dosage in alcohol-dependent patients. DESIGN: Preliminary retrospective descriptive study. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: 11 alcohol-dependent patients (9 males, 2 females, mean age 50.8 years, range 33 to 60 years). INTERVENTIONS: Ethanol substitution (ES) by parenteral application. MEASUREMENTS AND RESULTS: Ethanol kinetics were evaluated by repeated measurement of the blood ethanol concentration (BEC) over a period of at least 6 h parallel to the administration of ethanol. The average EER was found to be 28 mg/dl per h with a standard deviation of 11 mg/ dl per h. The minimum value was 18 mg/dl per h and the maximum 50 mg/dl per h. These EERs were significantly higher than the EERs known from forensic analysis. AWS was prevented in all 11 patients. CONCLUSIONS: Close control of BEC and precise adjustment of ethanol administration are necessary prerequisites for ES. The standard EER is not sufficient to define the appropriate ethanol dosage due to enormous variations in the ethanol metabolism of alcohol-dependent patients.

Adult↗

Interrelationship of smoking and alcohol dependence, use and urges to use.

OBJECTIVE: The relationship between tobacco dependence and alcohol dependence has received little empirical scrutiny. The present study of alcoholics in treatment for alcoholism investigated pretreatment tobacco and alcohol history and dependence, as well as subjective responsivity to alcohol cues. METHOD: Eighty-three male alcoholics underwent a questionnaire assessment of smoking and drinking pretreatment followed by a laboratory assessment of reactivity to alcohol cues. RESULTS: The analyses demonstrate that (1) pretreatment tobacco dependence and pretreatment alcohol dependence are related, (2) alcohol dependence predicts urges to smoke during alcohol treatment, (3) exposure to alcohol cues results in increased urge to smoke, (4) smoking when ill predicts urge to drink during alcohol cue exposure and (5) urge to smoke is positively correlated with urge to drink. CONCLUSIONS: These data, collected in a population of alcoholics not currently receiving smoking interventions, indicate that smoking may be a factor to address during alcohol treatment. The clinical importance of these data is discussed.

Adolescent↗

Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype.

BACKGROUND: Characteristic behaviors of some alcohol-dependent individuals, e.g., binge drinking, comorbid psychopathology, and some types of alcohol-related problems, have been linked to abnormalities in serotonergic neurotransmission. However, studies that have evaluated serotonergic pharmacotherapy for reducing drinking have yielded conflicting results. One explanation for these findings is a general failure to distinguish alcohol subgroups that may be differentiated on the basis of serotonergic abnormalities. However, in 1996, Kranzler and colleagues reported that Type B alcoholics, who are characterized by high levels of premorbid vulnerability, alcohol dependence severity, and comorbid psychopathology, showed less favorable drinking outcomes in response to treatment with fluoxetine, a serotonin reuptake inhibitor, than with placebo. This medication effect was not seen in Type A alcoholics, i.e., those with lower risk/severity of alcoholism and psychopathology. The aim of the present study was to explore the validity of differential responding by alcohol-dependent subtypes using the serotonin reuptake inhibitor, sertraline. METHODS: A k-means clustering procedure was applied to a sample of alcohol-dependent subjects enrolled in a 14-week, placebo-controlled trial of 200 mg/day of sertraline, classifying them into lower-risk/severity (Type A: n = 55) and higher-risk/severity (Type B: n = 45) subgroups. RESULTS: A significant interaction between alcoholic subtype and medication condition was found, confirming the findings of Kranzler and colleagues that alcoholic subtypes responded differentially to serotonergic medication. Somewhat at variance with their results, however, the present study showed that the lower risk/severity (Type A) subjects had more favorable outcomes when treated with sertraline compared to placebo. CONCLUSIONS: Alcoholic subtypes differentially responded to sertraline when used as a treatment to reduce alcohol drinking, with one subtype having more favorable outcomes. Subtyping alcoholics may help to resolve conflicting findings in the literature on serotonergic treatment of alcohol dependence.

Adolescent↗

Use of a single question to screen trauma patients for alcohol dependence.

BACKGROUND: Alcohol-dependent trauma patients are known to be at future risk for both recidivism and mortality. Psychological tools exist to screen for alcohol-dependent disorders, and among patients with alcohol-dependent disorders, a brief intervention has been shown to modify behavior. However, the training involved and time required to administer these tools may decrease their utility. We explored the possibility that yet simpler screening tools could be used. METHODS: A prospective consecutive study was designed whereby all adult patients admitted to the trauma service were asked to participate in the study. If consent was obtained, one trained member of the research team would apply a standard alcohol-misuse screening tool (i.e., the Alcohol Use Disorders Identification Test [AUDIT]). One hundred forty-nine patients met criteria and agreed to participate. Fully completed questionnaires were then subjected to statistical analysis. RESULTS: Among the 149 participating patients, 36% were women and 64% were men, and 146 had blood alcohol levels (BALs) drawn. Those 146 patients form the basis of this report. Fifty-seven of the 146 (39%) patients had positive BALs and, among them, 74% of men and 54% of women recorded screening results consistent with harmful or dependent drinking. Among those with negative blood alcohol levels, 8% of women and 13% of men had scores consistent with harmful or dependent drinking by the AUDIT score. In both groups of patients, a cutoff of three or more drinks per day as a response to question 2 on the AUDIT (i.e., "On a typical day when you are drinking, how many drinks do you have?") correlated strongly with scores on the entire screening tool (AUDIT) in identifying those at risk for alcohol misuse. CONCLUSION: It may be reasonable to substitute a single question for the entire AUDIT screening instrument to screen for those at risk for alcohol misuse. If so, this single question could easily be incorporated into the history taken among patients admitted to a trauma service. Confirmation with a larger study is recommended.

Alcoholic Intoxication↗

Alcohol dependence in adult children of alcoholics: longitudinal evidence of early risk.

This study investigates familial alcoholism effects and the comparative probability of risk for alcohol dependence in adult children of alcoholics (ACAs) with a control group of non-ACAs. A cohort of 12,686 young adults from the National Longitudinal Survey of Youth (NLSY) is examined over a five-year period and conventional and lineal intergenerational models of alcoholism transmission are assessed. The results of multivariate logistic regression analyses indicate that the risk is relatively greater for male ACAs; sons of alcoholics drink significantly more heavily, experience problems earlier, and develop alcohol dependence more extensively than female ACAs or non-ACAs of either gender. The extent of dependence found in subjects with a lineal history of alcoholism on the father's side of the family, as well as heavy drinking, cigarette smoking and drinking onset in adolescence should be considered as critical predisposing factors of high risk for dependence at later ages. These observations corroborate clinical studies and support a growing body of biopsychosocial research literature.

Adult↗

Neopterin levels in alcohol-dependent patients.

Chronic alcohol exposure appears to suppress cell-mediated immunity which may contribute to the high incidence of infections among alcohol-dependent patients. We measured serum neopterin, as a marker of macrophage function and T-lymphocyte activation, in 26 alcohol-dependent patients. The mean serum neopterin in these patients was significantly lower than the mean serum neopterin in matched controls. In those who abstained, the mean serum neopterin at 3 weeks rose and was no longer significantly different from controls. Our findings suggest that alcohol-dependent patients have suppressed macrophage function which may be reversible within 3 weeks of abstention.

Adult↗

[Biochemical markers in relation to the degree of alcohol dependence].

In 93 alcohol dependent patients following laboratory tests were done: gamma-glutamic transpeptidase (GGTP), aspartate aminotransferase (SGOT), mean erythrocyte volume (MCV), triglycerides (TGL), and HDL-cholesterol to whole-cholesterol ratio (HDLC%). The psychometric evaluation was made by MAST questionnaire and by authors clinical scale for the evaluation of alcohol dependence. Lover values of GGTP and SGOT were shown in patients during abstinence than in subjects continuing drinking. Patients more severely dependent showed higher HDLC%. The more frequent abnormalities reflected: GGTP (33.7%), MCV (33.7%), and HDLC (31.4%). The use of these 3 markers allowed to reveal abnormalities in 72.1% of subjects, while the use of all 5 markers - in 81.4%. The identification significance of markers was different in persons with more and less severe alcohol dependence. Three most sensible markers in the group of less dependent subjects were GGTP, MCV, TGL (60% of subjects showed abnormalities regarding these markers). Among more severe dependent subjects HDLC%, GGTP, and MCV were most sensible markers (78.4% of abnormalities). Using all 5 markers the abnormalities in the group of less severe dependent subjects were found in 71.4%, and in the group of more severe dependent patients--in 88.2%.

Adult↗

An item response analysis of the Alcohol Dependence Scale in treatment-seeking alcoholics.

OBJECTIVE: In this study we use methods based on Item Response Theory to examine in depth the psychometric properties of the Alcohol Dependence Scale (ADS). In particular, we examine the ability of each ADS item to discriminate among individuals across the continuum of alcohol dependence severity and also examine the extent to which item-response options provide useful and reliable information about the level of alcohol dependence. METHOD: Participants were 166 alcohol-dependent patients with elevated depressive symptoms. We conducted a maximum likelihood common factors analysis on the ADS, and then used a nonparametric kernel smoothing method to create Item Characteristic Curves (ICC) and Option Characteristic Curves (OCC) for each ADS item. On the basis of these curves, we identified items showing at least fair discrimination and modified the scoring of response options where indicated. We then created an empirically derived ADS score and correlated it with the original ADS and with other measures of alcohol involvement. RESULTS: Replicating previous studies, our results indicated a primarily unidimensional factor structure. A total of 12 of the 25 ADS items showed good discrimination, and examination of the OCC indicated that dichotomous scoring was most appropriate for these items. This 12-item abbreviation of the ADS was highly correlated with the original scale (r = 0.91), and showed similar patterns of correlations with other measures of alcohol involvement. CONCLUSIONS: Results suggest potential gains in measurement efficiency using methods based on Item Response Theory and indicate potential ordering of dependence symptoms based on item severities.

Adolescent↗

Carbohydrate-deficient transferrin and alcohol dependency: variation in response to alcohol intake among different groups of patients.

Carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) were evaluated as markers of alcohol dependency in two different groups of patients. Sensitivity of CDT was nearly 75% for patients hospitalized for detoxification, but lower than 50% for alcohol-dependent patients admitted to acute surgery. CDT correlated with self-reported alcohol consumption in both groups, and sensitivity increased with higher alcohol intake. Sensitivity of CDT for females in both groups was considerably lower than for males, although their alcohol consumption was not significantly different. Serum activity of GT showed almost identical performance as CDT when evaluated by receiver-operating characteristics curve analysis (ROC-analysis), but sensitivity and specificity of the two markers varied differently with both alcohol consumption and age. Among the surgical patients, the highest sensitivity of CDT was found for the middle-aged patients (36 to 50 years), whereas the highest sensitivity of GT was found for the eldest. A tendency for similar age-related differences were also observed among the patients warded for detoxification, but these differences were not statistically significant. A particular difference between the two groups was noted among the youngest patients (21 to 35 years), with a very low sensitivity of CDT (< 20%) for the surgical patients and a high sensitivity (77%) for the detoxification group. This difference was not only caused by differences in the present alcohol consumption, but would also be related to differences in drinking pattern or duration. Two commercial kits analyzing CDT were compared and ROC-analysis indicated identical performance of the two. However, a kit determining CDT as percentage of total transferrin showed a somewhat higher sensitivity among patients with low serum transferrin. We conclude that CDT and GT show variant responses to alcohol consumption in different groups of patients. The level of the two markers are related to sex, age, and alcohol consumption. Furthermore, the performance of both markers depend on the patients' history of alcohol abuse. CDT and GT are statistically independent markers and may therefore supplement each other.

Adult↗