Alcohol-dependent Men Research Articles

Recent developments in the pharmacotherapy of alcohol dependence.

The effectiveness of a treatment for alcohol dependence can be appropriately determined only after controlling for the usual clinical course of alcoholism, subgroups of alcohol-dependent individuals, and placebo effects. The results of appropriate treatment trials must also be interpreted in light of the side effects and costs, and there must be assurances that the overall improvement in functioning observed with the drug is significant enough to outweigh the liabilities. In addition, medications are almost always used in combination with education, counseling, and behavioral therapies, and the impact of these additional treatments must be considered. Viewed from this perspective, 3 medications are quite promising regarding their potential future impact in the alcohol field, including naltrexone, the medication with the most available data in the United States. There are additional data regarding buspirone and acamprosate. Intriguing results have also been generated regarding medications that affect serotonin and dopamine brain activity and with alcohol-sensitizing drugs such as disulfiram. However, none of these medications has been proven to be clinically effective in the routine treatment of the average alcoholic. It is hoped that future research will help identify subgroups of alcohol-dependent men and women who are most likely to respond to specific pharmacological treatments.

Alcohol dependence, family history, and D2 dopamine receptor function as neuroendocrinologically assessed with apomorphine

Fifteen alcohol dependent men with an alcohol dependent first degree relative (i.e. family history positive or FHP), 15 well matched alcohol dependent men without a family history for alcohol dependence (i.e. family history negative or FHN), and 15 healthy controls (CONTR) participated in this study. The three groups were compared according to their postsynaptic D2 dopamine receptor function as assessed by growth hormone release after stimulation with the dopamine receptor agonist apomorphine. Statistical evaluation was done by planned comparisons within a one-way ANOVA. Alcohol dependent subjects significantly differed from CONTRs as long as family history was not taken into account ( t(42) = 2.38; P = 0.022∗). When differentiating according to family history, both FHPs and FHNs maintained a blunted growth hormone response. However, the difference between FHNs and CONTRs, though present, dropped out of statistical significance ( t(42) = 1.65; P = 0.105); at the same time, the difference between FHPs and CONTRs became slightly stronger ( t(42) = 2.47; P = 0.017∗). In conclusion, our data give neuroendocrinological support to the assumption that a reduced D2 dopamine receptor function in alcohol dependent men is not only a state marker of residual heavy drinking but also a genetically determined trait marker.

The prevalence of major anxiety disorders in relatives of alcohol dependent men and women.

The relationship between alcohol dependence and lifelong major anxiety disorders is complex. The literature indicates a close association between anxiety symptoms and drinking behavior. However, it is difficult to determine whether the anxiety conditions are lifelong disorders or if they represent temporary organic conditions related to alcohol intoxication and withdrawal. One approach to understanding more about the relationships between alcohol dependence and major anxiety disorders is to observe the rate of anxiety-related diagnoses in close relatives of alcoholics. This approach evaluates whether alcoholism and major anxiety disorders might share a common genetic basis. The data presented here describe the rates of four major anxiety disorders in 591 interviewed first-degree relatives of alcohol dependent men and women. The data were gathered through face-to-face structured standardized interviews. The analyses reveal that after focusing on DSM-III-R anxiety disorders, controlling for the potential presence of temporary organic conditions in the subject and considering the impact of assortative mating in their parents, the life-time risk for panic disorder in close biological family members of alcoholics is 3.4%; for agoraphobia, 1.4%; for social phobia, 2.3%; and for obsessive-compulsive disease, 1.4%. These data do not indicate an exceptionally high rate of anxiety disorders among close relatives of alcoholics. While other mechanisms might contribute to relationship between alcoholism and major anxiety disorders, the results do not support evidence of a common genotype for the two disorders.

One‐year incidence rate of major depression and other psychiatric disorders in 239 alcoholic men

The rate of depressive symptoms among alcoholics is high, but many of these syndromes appear to be alcohol-induced mood disorders and might not represent major depressive episodes independent of heavy drinking. The present study examines one aspect of the relationship between alcoholism and depression by evaluating the incidence of new episodes of major depressive disorders among alcohol-dependent men during the year following treatment. One year following discharge from an alcohol treatment program, structured face-to-face interviews were carried out with 239 primary alcoholic men, as well as additional informants. Approximately 4% of the men developed depressive episodes while drinking heavily, but only 2.1% demonstrated major depressions independent of heavy alcohol intake. There was no evidence of an increased incidence of any other major psychiatric disorder during the year of follow-up. These results are consistent with prospective studies of children of alcoholics and of longitudinal evaluations of general population samples. They do not indicate that in the present sample most primary alcohol-dependent men have elevated rates for major depressive disorders independent of alcohol-induced mood syndromes. However, it is likely that in the context of heavy drinking severe, although temporary, depressive episodes are likely to be observed.

INFLUENCE OF TEMPERANCE ON SHORT-TERM MORTALITY AMONG ALCOHOL-DEPENDENT MEN IN SRI LANKA

The influence of temperance on short-term mortality was assessed in a group of alcohol-dependent men admitted to a rehabilitation unit in Sri Lanka. Of the 234 men initially admitted to the programme, 188 were followed up for at least 3 years (mean +/- SD 49.5 +/- 12.6 months) or until death. All 188 were totally abstinent from alcohol on leaving the 6 week residential module of the programme. During follow-up, 115 relapsed to continued heavy drinking, whereas 73 remained either totally abstinent or drank infrequently. There were no significant differences in the age, duration of dependence, number of previous interventions, duration of follow-up or smoking habits between the two groups of patients. The overall mortality for the whole sample population was 9.6%. The mortality among those who relapsed to heavy drinking (13.9%) was more than five times that of those who were abstinent or drank infrequently (2.7%) (P < 0.04). Fifteen of the 16 deaths (93.8%) among those who relapsed to heavy drinking were alcohol-related, and included five suicides and accidents whilst under the influence of alcohol. Temperance significantly reduces short-term mortality in alcohol-dependent men when compared to those who relapse to continued heavy drinking. This difference was primarily due to reduction in the risk of alcohol-related deaths.

Personality and Dopaminergic Function: Are there Correlations in Alcoholdependent Men?

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Suicide attempt histories in alcohol-dependent men: differences in psychological profiles.

Fifty-three alcohol-dependent men without additional Axis I disorders were divided into two groups based on past history of suicide attempts (SP = suicide positive, N = 15; SN = suicide negative, N = 38). Post-hoc analysis revealed that the two groups were matched for age, racial makeup, family history of suicide, and total number of years of drinking. A significantly higher percentage of SP group patients had personal and family histories of either illicit drug use, past psychiatric treatment, or both. Psychological profiles demonstrated exaggerated tendencies toward sociopathy, attitudinal deviance, heightened activity, anxiety, depression, hostility, and disordered thinking among the SP patients. These findings highlight the importance of designing individualized relapse prevention programs.

A pilot study of school-age children of men with moderate to severe alcohol dependence: maternal distress and child outcomes.

This pilot study examined maternal characteristics and children's internalizing and externalizing problems among 53 families (26 alcohol-dependent men, 27 controls) recruited from the general community in a north-east metropolitan area. Comparisons by family type revealed significant differences in maternal depression, social support, life events and children's anxiety, depression and problem behaviors. Factor analysis and hierarchical multiple regression revealed that a maternal distress factor accounted for significant amounts of variance in child outcome variables in addition to that accounted for by fathers' alcohol dependence symptoms. Future studies of school-age children of alcohol-dependent men should routinely sample indices of maternal distress to improve assessments of children's developmental contexts.

PET analysis of [ 11C]flumazenil binding to benzodiazepine receptors in chronic alcohol-dependent men and healthy controls

Benzodiazepine (BZ) receptor binding in the brain was determined in five chronic alcohol-dependent men and in five healthy male control subjects using [ 11C]flumazenil (Ro 15-1788) and positron emission tomography (PET). Magnetic resonance imaging was used to evaluate brain anatomy and pathology, and to define regions of interest in the brain. [ 11C]Flumazenil binding was quantified by applying a saturation procedure with two PET experiments, the first with high (400–3400 Ci/mmol) and the second with low (≈1 Ci/mmol) specific radioactivity. Radioactivity in the pons was taken as an estimate of free and nonspecifically bound radioligand. Equilibrium was defined to prevail when the derivative of specific binding (dC b(t)/dt) was equal to zero. The values were used in a Scatchard analysis for determination of the maximum density of binding sites ( B max ) and the equilibrium binding constant ( K d ). The mean values of B max and k d were about the same in the two groups, but the B max variance for the alcoholics was significantly greater for all regions of interest as compared with the healthy volunteers. The results may indicate that chronic alcohol consumption has multiple effects on the BZ receptor complex.

PET analysis of [c]Flumazenil binding to Benzodiazepine receptors in chronic alcohol-dependent men and healthy controls

Benzodiazepine (BZ) receptor binding in the brain was determined in five chronic alcohol-dependent men and in five healthy male control subjects using [ 11 C]flumazenil (Ro 15-1788) and positron emission tomography (PET). Magnetic resonance imaging was used to evaluate brain anatomy and pathology, and to define regions of interest in the brain. [ 11 C]Flumazenil binding was quantified by applying a saturation procedure with two PET experiments, the first with high (400–3400 Ci/mmol) and the second with low (≈1 Ci/mmol) specific radioactivity. Radioactivity in the pons was taken as an estimate of free and nonspecifically bound radioligand. Equilibrium was defined to prevail when the derivative of specific binding (dC b (t)/dt) was equal to zero. The values were used in a Scatchard analysis for determination of the maximum density of binding sites ( B max ) and the equilibrium binding constant ( K d ). The mean values of B max and k d were about the same in the two groups, but the B max variance for the alcoholics was significantly greater for all regions of interest as compared with the healthy volunteers. The results may indicate that chronic alcohol consumption has multiple effects on the BZ receptor complex.

Family Risk Factors, Parental Alcohol Use, and Problem Behaviors among School-Age Children

This study examined maternal ratings offamilyfunctioning and children's depression, anxiety, andproblem behaviors among 53 families (26 with alcohol-dependent men, 27 comparison families). Women with alcohol-dependent partners reported significantly more marital and family disruption, as well as higher levels of child problem behaviors. Both fathers' alcohol dependence and a family risk factor index accounted for significant amounts of variance in concurrent ratings of child functioning

A two-year follow-up study of alcohol dependent men rehabilitated at a special unit in a developing country.

Two hundred and thirty-four alcohol dependent men who had all failed to improve after previous hospital-based interventions were admitted to an intensive 6-week residential rehabilitation programme conducted at a special unit in Sri Lanka. Outcome was assessed at 2 years post-treatment, and 36% of dependent persons remained totally abstinent. During an extended period of follow-up (mean 39.2 months) a significant association was found between abstinence and having a life partner, stable family support, a higher income and regular employment. However, there was no significant association between abstinence and age, duration of alcohol dependence, level of education or type of employment. Although the majority of alcohol dependent persons did not benefit from the programme, our results compare favourably with those of similar studies done in developed countries.

The Alcohol Clinical Index in lower socioeconomic alcohol-dependent men.

The Alcohol Clinical Index, consisting of a 17-item Clinical Signs checklist and a 13-item Medical History questionnaire, was designed to provide an economic screening instrument for alcoholism not subject to self-report biases. There has been little validation work with this instrument. We therefore administered the Alcohol Clinical Index to a group of 40 alcohol-dependent men undergoing treatment at a VA Medical Center and a group of 17 nonalcoholic men being treated at an outpatient medical clinic at the same facility. The Clinical Signs checklist had high sensitivity, but poor specificity. Overall accuracy was 70% for a threshold score from 1 to 5. The Medical History questionnaire had more moderate sensitivity, but 100% specificity for a cutoff score of 2 or more. At a cutoff of 2, it had an overall accuracy of 84%. The high specificity of the Medical History questionnaire suggests that it could be used to help discriminate between alcoholics and nonalcoholics. Further study of these measures and individual items within the measures is recommended with different groups of alcohol users and nonusers.

Shared neuroendocrine patterns of post-traumatic stress disorder and alexithymia.

High norepinephrine/cortisol ratios have been shown to be useful indicators of post-traumatic stress disorder (PTSD). Alexithymia can result from overwhelming stress; thus, we hypothesized that sympathetic-adrenal medullary/hypothalamic-pituitary adrenal ratios would be positively associated with alexithymia severity. In the present study, we correlated 3-methoxy-4-hydroxyphenylethylene glycol (MHPG)/adrenocorticotropic hormone (ACTH) and MHPG/cortisol ratios with self-report Toronto Alexithymia Scale (TAS) scores in a group (n = 17) of nondepressed, formerly alcohol-dependent men. The correlations between the respective ratios and TAS scores were 0.515 (p = 0.034) and 0.561 (p = 0.019). We suggest that increasing degrees of alexithymia are accompanied by an increasing separation of these two endocrine systems and then speculate that this dissociation has an anatomical basis in the lateralization of emotions.

Disturbances of hypothalamic-pituitary-adrenal axis functioning during ethanol withdrawal in six men

Excessive exposure to glucocorticoids can have neurotoxic effects. The behavioral, cognitive, and neurochemical changes observed following the cessation of heavy drinking, therefore, may be associated with disturbances of the hypothalamic-pituitary-adrenal (HPA) axis. To investigate HPA axis disturbances during the ethanol withdrawal syndrome, the authors examined diurnal changes in plasma cortisol in six alcohol-dependent men following the abrupt discontinuation of alcohol intake. Plasma cortisol concentrations were quantified every 30 minutes for 24 hours in the early stage (1 day after cessation) and the middle to late stage (3 days after cessation) of the ethanol withdrawal syndrome as well as after the resolution of acute symptoms (8 days or more after cessation). Plasma cortisol concentrations were almost twice as high during acute withdrawal as they were following recovery. The duration of the cortisol diurnal cycle on the first day of withdrawal was negatively correlated with the severity of withdrawal. There is a marked activation of the HPA axis associated with the ethanol withdrawal syndrome. The authors hypothesize that this activation may account for some of the signs and symptoms of acute and subacute withdrawal. They discuss the potential long-term physiological effects of the episodic increases in cortisol associated with repeated episodes of ethanol withdrawal. The alterations in cortisol rhythmicity during early withdrawal may also have clinical implications.

Heart rate variability and cardiac autonomic function in men with chronic alcohol dependence.

Cardiac autonomic function was studied in 23 alcohol dependent men by standard tests of autonomic function and measurement of 24 hour heart rate variability. In all there was peripheral or central nervous system damage or both. Standard tests of autonomic function showed vagal neuropathy in seven. The remainder had normal autonomic function tests. Twenty four hour heart rate variability was measured as the standard deviation of the successive differences between RR intervals from an ambulatory electrocardiogram recording. Twenty four hour heart rate variability was significantly lower in both alcohol dependent groups than in controls, but the results in the two alcohol dependent groups were not significantly different from each other. The results of standard tests of autonomic function did not distinguish between the alcohol dependent men with normal autonomic function and controls. The differences in heart rate variability between this group and the controls may have been the result of the ability of this method to detect small changes in autonomic integrity. Cardiomyopathy may also account for some of these differences and such abnormalities should be excluded before results are to be regarded as a reflection of vagal function. Twenty four hour measurement of heart rate variability may be a more useful index of cardiac vagal neuropathy than currently available tests of autonomic function.

Psychiatric disorders in the first-degree relatives of probands with bulimia nervosa.

Data from a family study of psychiatric disorders showed higher rates of major affective disorders, eating disorders, and alcoholism in first-degree relatives of 40 bulimic probands than in first-degree relatives of 24 control subjects. More importantly, the data showed higher rates of major affective disorders in relatives of bulimic probands who themselves had no history of major affective disorders than in relatives of control subjects. This significant finding indicates a familial relationship between bulimia nervosa and major affective disorders, which suggests the possibility of a common diathesis.

Alcoholism and depressive symptomatology among convicted DWI men and women.

Interrelationships between DSM-III-based alcoholism diagnostic groups and depressive symptomatology were assessed for a sample of 461 convicted DWI offenders. The highest rate of depressive symptomatology was reported by persons diagnosed as alcohol dependent, and such findings were robust across male and female offenders. However, a significant interaction effect was found in which alcohol-dependent women reported higher levels of depressive symptomatology than alcohol-dependent men. With the exception that men reported significantly more previous DWI arrests than women, few differences were found between the gender groups with respect to a range of demographic variables, alcohol use and alcohol-related problems.

Alcohol-dependent men and women in detoxification: some comparisons.

Alcohol-dependent women undergoing detoxification treatment in psychiatric wards are compared to men with respect to sociodemographic and treatment-oriented variables. For these comparisons, patient documentation from all psychiatric hospitals in one large West German city were analyzed. Representativeness is shown by data of the general population of corresponding age. Findings are presented in relation to data of long-term inpatient therapy. Results show that the detoxified women are socially less poorly integrated than men and suggest that our common ideas about a drinking career are based on experience with male alcoholics.

A CONTROLLED TRIAL OF INPATIENT AND OUTPATIENT TREATMENT OF ALCOHOL DEPENDENCY

In the U.K., the treatment of alcoholism has been based more on inpatient care than on outpatient clinics. Forty alcohol-dependent men who had no other severe physical or mental illness and who agreed to accept either treatment were randomised to inpatient or outpatient therapy. The average stay in hospital was 8·9 weeks for inpatients, while outpatients on average spent 7·7 weeks in " intensive treatment". A correlation analysis showed a relation between demographic and personality factors, drinking chronology, and " complications of drinking" but did not reveal any significant prognostic factors. All patients were followed up to 1 year with monthly assessment of progress made on a 2-point scale by independent raters. There was no significant difference between groups. The bearing of these results on the planning of future treatment is discussed and it is suggested that emphasis should now be on development of the comprehensive treatment service, which would integrate inpatient and outpatient services and also provide hostel care. The specialised inpatient unit is probably of value, but criteria for admission need to be much more strictly defined.