Cortical and diencephalic lesions in Korsakoff's syndrome: a clinical and CT scan study

Twenty-five male alcoholic Korsakoff patients were compared with age and sex-matched non-Korsakoff chronic alcoholics and healthy volunteers on clinical and CT brain scan parameters. The scans were assessed by planimetry, visual grading procedures and computerized analysis. Reliable measures of third ventricular size were developed. The Korsakoff patients had wider third ventricles, larger lateral ventricles and wider interhemispheric fissures than the comparison groups; but sulcal and Sylvian fissure widths were equivalent in Korsakoff and non-Korsakoff alcoholics. The results suggest that, in addition to their well-established diencephalic lesions, many Korsakoff patients have sustained widespread cerebral damage. Shrinkage in the frontal brain regions appears to be especially pronounced. The implications for a dual aetiology of alcoholic Korsakoff's syndrome involving thiamine deficiency and features associated with alcoholism, probably direct alcohol neurotoxicity, are discussed.     

Alcoholics anonymous and relapse prevention as maintenance strategies after conjoint behavioral alcohol treatment for men: 18-month outcomes

Ninety men with alcohol problems and their female partners were randomly assigned to 1 of 3 outpatient conjoint treatments: alcohol behavioral couples therapy (ABCT), ABCT with relapse prevention techniques (RP/ABCT), or ABCT with interventions encouraging Alcoholics Anonymous (AA) involvement (AA/ABCT). Couples were followed for 18 months after treatment. Across the 3 treatments, drinkers who provided follow-up data maintained abstinence on almost 80% of days during follow-up, with no differences in drinking or marital happiness outcomes between groups. AA/ABCT participants attended AA meetings more often than ABCT or RP/ABCT participants, and their drinking outcomes were more strongly related to concurrent AA attendance. For the entire sample, AA attendance was positively related to abstinence during follow-up in both concurrent and time-lagged analyses. In the RP/ABCT treatment, attendance at posttreatment booster sessions was related to posttreatment abstinence. Across treatment conditions, marital happiness was related positively to abstinence in concurrent but not time-lagged analyses.     

Increased total serum IgE in alcoholics

Total serum IgE concentrations were measured in 106 male alcoholics with current alcohol abstinence of varying duration. The influence of smoking habits and clinical atopy on IgE levels was considered. The majority (91%) of the alcoholics were smokers and 26% suffered from possible clinical atopy. The geometric mean IgE in non-atopic, smoking alcoholics was 42 kU/l and significantly higher than the mean IgE level, 19 kU/l, in age-matched, smoking, non-atopic male participants in a general health survey (p less than 0.001). The IgE levels declined with the length of the alcohol abstinence period. Alcoholics, serially followed after a heavy drinking spree, showed a uniform pattern of declining IgE levels during a fortnight of abstinence (p less than 0.001). No link was noted between total IgE levels and the extent of liver affection as estimated by various serum variables (bilirubin, aminotransferases, gamma-GT, IgG, IgA and IgM) or galactose tolerance test. The increased IgE levels in alcoholics are suggested to reflect an influence of ethanol on T lymphocytes regulating the IgE synthesis. Such a proposed effect of ethanol on cellular immunity may contribute to certain organic alcohol diseases, but does not appear to influence the frequency of clinical atopy, being similar in our patient group and in the general population of the same geographic area.     

Laboratory test changes in young abstinent male alcoholics

Data collected over time from an abstaining young alcoholic population were analyzed together with data from a nonalcoholic population, which served as a reference group. The laboratory tests of the abstaining alcoholics were measured at baseline (zero weeks), three weeks, and six weeks, while those of the nonalcoholic group were measured once, at baseline. The analysis attempts to reveal how abstinence from beverage alcohol consumption in an alcoholic population affects 25 commonly ordered laboratory tests over time and whether cigarette smoking mediates any observed effects. The primary findings of this detailed examination of clinical chemistries in abstaining alcoholics indicate that drinking and smoking have independent effects and that the effects of drinking persist even after six weeks of abstinence.     

Learning impairment in male and female alcoholics.

Male VA alcoholics have been found to perform significantly poorer than nonalcoholics in face-name learning. Can these results be (a) replicated in a sample of male alcoholics from community treatment programs, (b) extended to female alcoholics, and (c) accounted for by childhood symptoms of attention deficit, conduct, and learning disorders? Seventy-six male and 66 female alcoholics were compared to 48 male and 49 female nonalcoholic controls on a 12-item face-name learning test. Both male and female alcoholics had poorer learning scores than their respective control groups. Learning scores were unrelated to self reports of childhood attention deficit disorder, conduct disorder, and learning problems. Whether alcoholics' impaired face-name learning is due to the direct effect of alcohol on the brain or is a concomitant of alcoholics' disrupted interpersonal relationships remains to be investigated.     

Dysmorphology and microstructural degradation of the corpus callosum: Interaction of age and alcoholism

Chronic alcohol abuse is a ubiquitous health and societal problem, with a growing prevalence in the older population. Alcoholism is a source of substantial deterioration in brain tissue and has been consistently observed in vivo and postmortem in white matter. To quantify the potential compounded effect of age and alcoholism, we used conventional structural MRI and diffusion tensor imaging (DTI) to examine the macrostructural and microstructural integrity of the corpus callosum, one of the most prominent white matter structures of the brain, in 131 adults, age 27-75 years. Compared with the 74 controls, the 40 alcoholic men and 17 alcoholic women, who were abstinent from alcohol for an average of 3 months, showed similar patterns and extents of callosal shrinkage, which was greatest in the genu and body and less prominent in the splenium. Microstructural integrity was measured with DTI as fractional anisotropy, an index of intravoxel orientational coherence of white matter fibers, and bulk mean diffusivity, an index of the amount of intravoxel water motility. The macrostructural shrinkage was accompanied by abnormalities in anisotropy and diffusivity of the microstructural environment of these callosal regions, indicative of disruption of structural constituents of local brain white matter. Correlational analyses revealed an age-alcohol interaction, where older alcoholics had smaller genu and splenium and higher diffusivity in these regions than younger alcoholics. Significant correlations between regional MRI and DTI measures and performance on working memory, visuospatial ability, and gait and balance provided evidence for the functional ramifications of the callosal abnormalities in the alcoholics. Thus, despite abstinence from alcohol, the interaction of age and recent alcoholism history exerted a compounded untoward effect on callosal macrostructure and microstructure.     

Recovery of visual-spatial learning and memory in chronic alcoholics

Administered the Memory-for-Designs Test and a verbal and Visuospatial paired associate learning test to separate groups of alcoholics (N = 32) 3 and 11 weeks abstinent from alcohol and to a matched control group (N = 16). Alcoholics were not impaired in verbal learning. Alcoholics 3 weeks abstinent performed significantly less well than controls on all nonverbal tasks and less well than 11-weeks alcoholics on one nonverbal measure. No significant differences were found between 11-week alcoholics and controls. The results suggest that some recovery of function may occur in alcoholics after 10 weeks of abstinence. The data also support the hypothesis of impaired right hemisphere in alcoholics.     

Gender and personality in alcoholism

The topic gender and personality in alcoholism is discussed on the background of a research project on clinical aspects of alcoholism at the University of Würzburg, Germany. The data of this study are presented in the context of two questions: Which personality differences are there between women and men dependent on alcohol, and is there a connection between these personality differences and features of the alcohol dependence? Additionally, we take a look at gender-related differences in the development of alcoholism. In a first step, gender differences in the development and the course of alcoholism are investigated. The data revealed only weak differences between female and male alcoholics when important confounding variables like age and education are taken into consideration. Secondly, the female and male alcoholics are matched according to age and education and their personality structures are compared by using several well-established and standardized self-report questionnaires. No serious gender differences concerning the main characteristics of alcohol dependence could be discovered. However, some remarkable personality differences between female and male alcoholics are found: women scored significantly higher on Neuroticism and Harm-Avoidance while men reached significantly higher scores on Venturesomeness and Sensation-Seeking. In order to detect a possible connection between alcoholism and gender-related personality differences, both males and females are subdivided into two groups using the scores of Neuroticism, Harm-Avoidance, Venturesomeness and Sensation-Seeking, respectively. We have found no indication for a gender-specific relevance of personality differences between female and male alcoholics with regard to Harm-Avoidance, Venturesomeness or Sensation-Seeking. However, differences in Neuroticism have revealed a greater relevance in alcohol-dependent women than in men.     

The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men

To identify the association between the polymorphisms of genes encoding alcohol metabolizing enzymes and alcoholism, the alcohol dehydrogenase 2 (ADH2), alcohol dehydrogenase 3 (ADH3), aldehyde dehydrogenase 2 (ALDH2), and cytochrome P450 2E1 (CYP2E1) genes were studied in 101 male Mexican American alcoholics. One hundred and four Mexican American nonalcoholic males served as controls. The allele frequency of ADH2*2 (4.3%) and ALDH2*2 (0%), which are considered as protective alleles against alcohol drinking, is very low in Mexican Americans and no association is found between these alleles and alcohol dependence. A strong association was found between ADH3 genotype and alcoholism; the percentage of subjects who carry the ADH3*2 allele was significantly higher in alcoholics (64.4%) than controls (50%). Association was also found between the CYP2E1 RsaI c2 allele and alcohol dependence; the percentage of subjects who carry the RsaI c2 allele was significantly higher in alcoholics (34.7%) than in nonalcoholics (22.1%). The subjects whose alcohol drinking onset age is younger than 25 have much higher CYP2E1 c2 allele frequency than those whose alcohol drinking onset age is older than 25 (22.1% vs 15.7%). Among 101 alcoholics, only 18 subjects carry neither ADH3*2 nor CYP2E1 c2 alleles. For those subjects who have an ADH*1/*1 background, a strong association is found between CYP2E1 RsaI/DraI genotype and alcoholism; the CYP2E1 RsaI c2 and DraI C allele frequencies are much higher in alcoholics than in nonalcoholics (26.4% vs 9.6% for c2 and 27.8% vs 13.5% for C allele). Taken together, ADH3*2 and CYP2E1 c2/C alleles might independently contribute to the development of alcoholism in Mexican American men.     

Controlled drinking training with a female alcoholic

Controlled drinking training based upon an avoidance conditioning paradigm (Mills, Sobell & Schaefer, 1971) has previously been demonstrated to offer an alternative to abstinence for some alcoholics. This paper describes the treatment and outcome of controlled drinking training as applied to a 33 year old female who had previously attempted abstinence and who could engage in sexual intercourse only after drinking.     

Differences in platelet enzyme activity between alcoholics and nonalcoholics

Blood platelets are an accessible tissue that reflects the activity of many enzymes found in the brain. To investigate the possible effect on such enzymes of long-term consumption of large quantities of ethanol, we assayed the activities of two enzymes, monoamine oxidase and adenylate cyclase, in platelet membranes of men with alcoholism and controls matched for sex and age. We also compared these two groups in terms of the inhibition of platelet monoamine oxidase activity by ethanol in vitro (400 mM), and in terms of the stimulation of adenylate cyclase activity by various agents. There was no significant difference in monoamine oxidase activity between the alcoholics and the controls. However, the inhibition of monoamine oxidase by ethanol was significantly higher in the platelets of alcoholics. The basal activity of adenylate cyclase was the same in platelets from the alcoholics and the controls, but the platelet adenylate cyclase activity after stimulation with guanine nucleotide, cesium fluoride, or prostaglandin E1 was significantly lower in alcoholics. These differences were not associated with age, race, smoking, or illicit drug use, and there was no significant correlation with the duration of problems with alcohol. The changes were long-lasting; cesium fluoride-stimulated adenylate cyclase activity was lower in alcoholic subjects who had abstained from alcohol for one to four years. Discriminant analysis showed that the use of values for the inhibition of monoamine oxidase activity by ethanol and cesium fluoride-stimulated adenylate cyclase activity correctly classified 75 percent of the alcoholics and 73 percent of the controls. These measures may be of value either as indexes of excessive alcohol consumption or as an indication of a predisposition to alcoholism.     

Alcoholics' self-assessment of their neuropsychological functioning in everyday life

Self-reports of impairment in everyday cognitive and perceptuomotor functioning for the 6 months that preceded treatment were investigated in 60 male, middle-aged alcoholics and for a comparable time period in 60 nonalcoholic controls matched on age, education, and Shipley Vocabulary age. Alcoholics reported significantly more everyday impairment than did controls in memory, higher cognitive functions, language skills, and perceptual-motor function. Laboratory tests of neuropsychological performance revealed that the alcoholics were significantly poorer than controls on measures of memory, higher cognitive functions, and overall neuropsychological functioning, but test performances essentially were uncorrelated with self-reported everyday impairment and with self-reported levels of depression and anxiety. However, in both groups, measures of depression and anxiety were correlated significantly with self-perception of impairment. In alcoholics, quantity-frequency of drinking (QFI) was also correlated with reported impairment; chronicity was not. Multiple regression analyses indicate that in alcoholics, both quantity-frequency measures of alcohol intake and affective distress (depression, anxiety) made independent and roughly equal contributions to reported everyday impairment; in controls, only affective distress contributed significantly.     

Investigation of Cloninger's subtypes in a male alcoholic sample: Applications and implications

Cloninger's Type 1/Type 2 classification scheme was examined in 82 male alcoholics. Only 16% were classified by presence/absence of Type 1/Type 2 symptoms. When age of symptom onset was considered, 75.6% were classified into early (ESO) and late symptom onset (LSO) groups. Relatively few group differences were found: ESOs were younger, had lower SES, began drinking earlier, reported greater frequency of maternal alcoholism and more severe paternal alcoholism, and reported more antisocial behaviors. ESO/LSOs did not differ on neuropsychological performance, although both performed poorer then controls. Differences between these findings and those found with female ESO/LSO alcoholics are discussed and clinical implications considered. © 1996 John Wiley & Sons, Inc.     

Discriminating neuropsychological sequelae of head injury from alcohol-ABUSE-induced deficits: A review and analysis

Alcohol abuse is linked strongly with neuropsychological deficits that may resemble deficits seen in head-injured individuals. Heavy daily drinking appears more damaging than episodic abusive consumption. Cognitive deficits associated with alcohol include abstraction, perceptuospatial, and problem- solving skills. Verbal abilities are spared. For alcoholics younger than 40, abstinence is associated with improved functioning. For those over 40, deficits may be permanent. Intelligence tests are unlikely to pick up alcohol-induced deficits. Points for neuropsychologists to consider in differentiating between head injury and alcohol-induced deficits include abstinence from drinking prior to testing, intactness of remote memory and verbal functions, and changes in tolerance for alcohol.     

Memory and ventricular size in alcoholics

The relationship between memory performance and CT scan measures of ventricular size was investigated in a sample of 39 chronic alcoholics and 39 controls. Measures of verbal, non-verbal, recognition and recall memory were derived from the tests administered and were viewed in relation to the lateral ventricle and third ventricular size measurements. The results showed that the memory performance of male alcoholics was significantly related to measures of third ventricular size, but probably not to measures of the lateral ventricles. An association between verbal memory performance and CT scan measures was found in the male controls.     

Relationships among aging, IQ, and intracranial volume in alcoholics and control subjects

The current article examined the relationships among aging, intelligence, intracranial volume, and brain shrinkage in alcoholics and nonalcoholic controls. Magnetic resonance imaging was used to measure intracranial and cerebral volumes in 146 subjects with alcohol use disorders and 42 comparison subjects who were not alcoholic. The authors' findings show that performance on Block Design decreases as alcoholics age, and this decrease is predicted by brain shrinkage. This is consistent with a process of cumulative brain damage related to alcohol use. However, the authors' data also show that vocabulary does not decrease with age and is correlated with premorbid brain size as measured by intracranial volume, suggesting that lower verbal ability precedes heavy alcohol use and may be a risk factor for alcoholism.     

Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk

BACKGROUND: Substantial evidence exists for an important genetic contribution to alcohol dependence risk in women and men. It has been suggested that genetically determined differences in alcohol sensitivity may represent one pathway by which an increase in alcohol dependence risk occurs. METHODS: Telephone interview follow-up data were obtained on twins from male, female and unlike-sex twin pairs who had participated in an alcohol challenge study in 1979-81, as well as other pairs from the same Australian twin panel surveyed by mail in 1980-82. RESULTS: At follow-up, alcohol challenge men did not differ from other male twins from the same age cohort on measures of lifetime psychopathology or drinking habits; but alcohol challenge omen were on average heavier drinkers than other women. A composite alcohol sensitivity measure, combining subjective intoxication and increase in body-sway after alcohol challenge in 1979-81, exhibited high heritability (60 %). Parental alcoholism history was weakly associated with decreased alcohol sensitivity in women, but not after adjustment for baseline drinking history, or in men. High alcohol sensitivity in men was associated with substantially reduced alcohol dependence risk (OR = 0.05, 95% CI 0.01-0.39). Furthermore, significantly decreased (i.e. low) alcohol sensitivity was observed in non-alcoholic males whose MZ co-twin had a history of alcohol dependence, compared to other non-alcoholics. These associations remained significant in conservative analyses that controlled for respondents' alcohol consumption levels and alcohol problems in 1979-81. CONCLUSIONS: Men (but not women) at increased genetic risk of alcohol dependence (assessed by MZ co-twin's history of alcohol dependence) exhibited reduced alcohol sensitivity. Associations with parental alcoholism were inconsistent.     

Familial distribution of alcohol use: II. Assortative mating of alcoholic probands

Comparisons of the drinking styles of family members of alcoholic probands with those of probands' spouses and spouses' family members were made to investigate factors that may contribute to similarity in alcohol use of spouses. Some support was found for the parental image theory, which predicts that a person will seek a mate with traits liked and without traits disliked in the opposite-sex parent. Alcoholic male probands tended to find spouses who were the daughters of alcoholics. Alcoholic female probands were found to have a high frequency of both alcoholic fathers and husbands, but they do not necessarily occur together. Phenotypic or primary assortative mating/contagion appears to explain more of the interspouse association than social or secondary homogamy.     

Computed axial brain tomography in long-term benzodiazepine users

Twenty patients who had taken long-term benzodiazepines were submitted to brain CT scan examinations. Some scans appeared abnormal. The mean ventricular/brain area measured by planimetry was increased over mean values in an age- and sex-matched group of control subjects but was less than that in a group of alcoholics. There was no significant relationship between CT scan appearances and the duration of benzodiazepine therapy. The clinical significance of the findings is unclear.     

The role of alcohol in suicide: a case-control psychological autopsy study

BACKGROUND: The purpose of the study was to estimate the proportion of alcohol abuse and dependence (AAD) among suicides and controls, and to compare the incidence of AAD documented by clinicians with diagnoses derived from a research protocol. METHOD: AAD according to DSM-IV was diagnosed on the basis of interviews with relatives of people who committed suicide and with controls. A total of 427 people who committed suicide during one year were paired by region, gender, age and nationality with controls randomly selected from general practitioners' lists. RESULTS: Alcohol abuse was found in 10% and alcohol dependence in 51% of suicide cases. The corresponding figures for controls were 7% and 14% respectively. AAD was a statistically significant predictor of completed suicides, while abstinence was a significant predictor for female suicides and former use a significant predictor for older male suicides. AAD was diagnosed in 68% of male and 29% of female suicides. Middle-aged (35-59 years) males who committed suicide had the highest risk of alcohol dependence. Among suicide cases only 29% had received a lifetime diagnosis of AAD, against 23% of controls. CONCLUSIONS: AAD was significantly more prevalent among suicides than controls. Overall, the proportion of male suicides affected by alcohol was the same in the present psychological autopsy study as in our previous findings for Estonia on the aggregate level, while the share of female suicides with an AAD diagnosis was dramatically higher on the individual level. AAD is markedly underdiagnosed by general practitioners and clinicians.