Psychiatric Comorbidity in Alcoholism: Importance of Ascertainment Source

Although psychiatric comorbidity is often observed among individuals in treatment facilities for alcoholism, the prevalence and pattern of psychiatric comorbidity among alcoholic cirrhotics has not been well characterized. The present study aimed first to compare the prevalence of psychiatric comorbidity in cirrhotic individuals with alcoholism ascertained from a gastroenterology service with alcoholics ascertained from a treatment facility for alcoholism. Consistent with the findings of other investigators, the data suggest that there is a great degree of variability regarding the severity of alcoholism in alcoholic cirrhotic individuals. Furthermore, cirrhotics with alcoholism exhibited a less severe clinical picture of alcoholism as measured by less alcohol dependence and lower prevalence of psychiatric comorbidity than individuals in treatment for alcoholism. The main conclusion of this study is that ascertainment source is an important determinant of psychiatric comorbidity observed in alcoholic samples.     

Personality and Substance Use Disorders: I. Effects of Gender and Alcoholism Subtype

The relationship between alcoholism and self-rated personality was explored in a community-ascertained sample of 303 male and 103 female alcoholics, and 304 male and 770 female nonalcoholics. Alcoholics met DSM-Ill-R lifetime criteria for alcohol dependence; personality was assessed using the Multidimensional Personality Questionnaire. Compared with controls, alcoholics scored significantly higher on all indicators of negative emotionality, and consistently lower on all indicators of constraint. Individual effect sizes were moderate in both the male and female samples. A subsample of severe male alcoholics, identified by cluster analysis, was characterized by relatively early onset of problem drinking and relatively high antisociality and familial loading of problem drinking; they were also more extreme than moderate male alcoholics on negative emotionality and constraint. When taken in aggregate, personality risk appears to be associated with a continuum of alcoholic risk such that individuals extreme in both negative emotionality and behavioral disinhibition have especially high rates of alcoholism.     

Working and Episodic Memory in HIV Infection, Alcoholism, and Their Comorbidity: Baseline and 1-Year Follow-Up Examinations

Background:  Selective memory deficits occur in individuals with human immunodeficiency virus (HIV) infection and those with chronic alcoholism, but the potential compounded effect of these conditions is seldom considered, despite the high prevalence of alcohol use disorders in HIV infection.
Methods:  Here, we examined component processes of working and episodic memory in HIV infection and chronic alcoholism (ALC) in 4 subject groups (HIV, ALC, HIV + ALC, and normal controls) at baseline and 1-year follow-up. Accuracy scores, response times, and rate of information processing were assessed with subtests of the computerized neuropsychological test battery, the MicroCog.
Results:  Although individuals with either HIV infection or alcoholism generally performed at normal levels, individuals comorbid with HIV infection and alcoholism were impaired relative to controls and to the single diagnosis groups on selective memory processes. Immediate episodic memory was impaired, whereas working memory remained intact. Ability to retain information over time was not impaired in the clinical groups. Little performance change between groups was detected over 1 year. Results could not be explained by amount of alcohol consumed over a lifetime, CD4 cell count, AIDS diagnosis, or HAART medication.
Conclusions:  This study provides behavioral support for adverse synergism of HIV infection and chronic alcoholism on brain function and is consistent with neuroimaging reports of compromised hippocampal and associated memory structures related to episodic memory processes in these 2 conditions.     

Examination of the Tridimensional Personality Hypothesis of Alcoholism Using Empirically Multivariate Typology

Cloninger (1987) has hypothesized a tridimensional personality theory for two types of alcoholism, type 1 and type 2, that exhibit oppodng clinical characteristics and personality traits. The Tridimensional Personality Questionnaire (TPQ) is designed to test this hypothesis on three independent dimensions—novelty seeking (NS), harm avoidance (HA), and reward dependence (RD)—to evaluate the personality trait. We examined the tridimensional personality hypothesis by comparing TPQ scores between two empirically derived multivariate types of alcoholism.
The present study included 191 male subjects with alcoholism. A cluster analysis was conducted using clinical characteristics, and two empirical types, type A and type B, were identified. Type A similar to Cloninger's type 1 and type B is similar to type 2. The TPQ scores given to these two empirical types were compared. Scores on the NS and RD scales were in good agreement with the hypothesis, whereas the HA score was discordant with the hypothesis. HA is highly correlated with the depression scale score that is elevated in type B. We discussed the possibility that type B, which may be called a familial early-onset alcoholism, is related to character spectrum disorder.     

A Comparison of the Alcohol Dependence Scale and Clinical Diagnosis of Alcohol Dependence in Male Medical Outpatients

The Alcohol Dependence Scale (ADS) is a brief self-report instrument designed to assess the alcohol dependence syndrome. Although previous studies have reported its validity, it has only been studied in populations who were presenting for assessment or treatment of alcohol problems, and recent studies have shown lower mean scores than would be expected. To assess its utility in a primary medical setting, we retrospectively examined our experience in two groups of medical outpatients: an early intervention group and a group of medically ill alcoholics. We administered the ADS to 61 male veterans being referred to a special clinic for alcohol-related medical problems. Subjects were also assessed for alcohol dependence by experienced clinicians using a DSM-III-R checklist. ADS scores overall were much lower than would be expected, especially in the medically ill alcoholics. When subjects were dichotomized into dependent or nondependent, there was poor agreement between the two methods. The correlation between the scores was significant, however, end lowering the cut-point on the ADS from 13/14 to 213 improved agreement. Medically ill alcoholics who are not presenting for assessment or treatment of alcohol problems may either lack insight into their drinking habits or may be reluctant to disclose them. Although conclusions from this study are tentative until more formal studies are done, it may be most prudent to use other instruments, such as the Michigan Alcoholism Screening Test, in medical outpatients. If the ADS is used, lowering the cut-score to 213 may reduce false negatives. Further research on the use of the ADS in different settings and with different populations is clearly needed.     

Bromocriptine in the Treatment of Alcohol Dependence

A double-blind controlled study of the effects of bromocriptine on drinking behavior and associated symptoms in ambulatory alcoholics showed a marked improvement in both treatment and control groups. However, significant differences in favor of the medication were observed in psychopathological measures, and trends in the same direction in most of the other efficacy parameters.     

MAOA-uVNTR Polymorphism May Modify the Protective Effect of ALDH2 Gene Against Alcohol Dependence in Antisocial Personality Disorder

Background:  Antisocial alcoholism is related to dopamine and serotonin which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2). The objective of this study is to determine whether the interaction between the MAOA and the ALDH2 genes is associated with subjects with antisocial personality disorder (ASPD) having alcoholism.
Methods:  A total of 294 Han Chinese men in Taiwan including 132 ASPD with alcoholism (Antisocial ALC) and 162 without alcoholism (Antisocial Non-ALC) were recruited in this study. Alcohol dependence and ASPD were diagnosed according to DSM-IV criteria. Genotypes of ALDH2 and MAOA-uVNTR were determined using PCR-RFLP.
Results:  A significant difference of ALDH2 polymorphisms ( p  = 3.39E-05), but not of MAOA , was found among the 2 study groups. However, only after the stratification of the MAOA-uVNTR (variable number of tandem repeat located upstream) 3-repeat , a significant association between Antisocial Non-ALC and ALDH2*1/*2 or *2/*2 genotypes was shown ( p  = 1.46E–05; odds ratio = 3.913); whereas stratification of MAOA-uVNTR 4-repeat revealed no association. Multiple logistic regression analysis further revealed significant interaction of MAOA and ALDH2 gene in antisocial ALC (odds ratio = 2.927; p  =   0.032).
Conclusion:  The possible interaction of MAOA and ALDH2 gene is associated with Antisocial ALC in Han Chinese males in Taiwan. However, the protective effects of the ALDH2*2 allele against alcoholism might disappear in subjects with ASPD and carrying MAOA-uVNTR 4-repeat allele in the Han Chinese male population.     

Comorbidity of alcohol abuse and dependence with medical conditions in 2 American Indian reservation communities

BACKGROUND: The objective was to examine the association of self-reported Diagnostic and Statistical Manual-IV edition alcohol abuse and dependence with medical conditions among American Indians (AIs). METHODS: We analyzed data previously collected in a large epidemiological study of members of 2 culturally distinct AI tribes from the Southwest (SW; n = 1,446) and the Northern Plains (NP; n = 1,638) living on or near their reservations. Associations of combined self-reported alcohol abuse and alcohol dependence with 19 medical conditions were examined through multinomial logistic regression. RESULTS: Medical conditions that had significant relationships with alcohol abuse/dependence were sprains and strains [odds ratio (OR) 2.04, p < 0.001], hearing and vision problems (OR 2.05, p < 0.001), kidney and bladder problems (OR 1.55, p < 0.01), head injuries (OR 2.20, p < 0.001), pneumonia/tuberculosis (OR 1.49, p < 0.01), dental problems (OR 1.89, p < 0.001), and liver problems/pancreatitis (OR 2.18, p < 0.001). The total count of medical conditions was also significantly related to alcohol abuse/dependence, with a higher count being associated with the outcome (OR 1.17, p < 0.001). CONCLUSIONS: In this community-based study of rural AIs, diverse medical conditions were associated with alcohol abuse and dependence. Further research should examine, and confirm, the nature, extent, and tribal variation of the medical consequences of alcohol abuse and dependence in these unique populations.     

Antisocial Tendencies and Cortical Sensory-Evoked Responses in Alcoholism

Alcohol-dependent patients with antisocial, aggressive, and impulsive behaviors form a subgroup, in which a dysfunction of the brain serotonin system is discussed as a pathogenetic factor. Early onset and a transmission from fathers to sons (type II alcoholism; Clon-inger, 1987) are supposedly further characteristics of this subgroup. The response pattern of primary auditory cortices to auditory stimuli with different intensities is discussed as a noninvasive indicator of the level of central serotonergic neurotransmission. A strong intensity dependence of these responses is supposed to indicate low serotonergic neurotransmission and vice versa. A strong intensity dependence is therefore expected to characterize patients with antisocial tendencies. Auditory-evoked potentials (N1/P2 component) to stimuli in five different intensities were recorded in 53 hospitalized patients after 1 week of withdrawal. Dipole source analysis was performed to separate responses of primary and secondary auditory cortices. Patients with antisocial tendencies showed a significantly stronger intensity dependence of their evoked responses of primary auditory cortices (tangential dipoles). Age at onset and family history were not related to the intensity dependence of the evoked responses. The results support the notion that alcohol-dependent patients with strong intensity dependence and antisocial tendencies form a subgroup with a serotonergic hypofunction. These patients may respond favorably to a relapse prevention with serotonergic drugs.     

Axis I and Axis II Comorbidity Among Alcohol-Disordered Men in a Sample of Vietnam-Era Veterans

The authors examine the scope of alcoholic comorbidity by evaluating the full range of coexisting Axis II personality disorders (PDs) in conjunction with selected Axis I disorders. Prevalence data are reported for a large sample of male, Vietnam-era military veterans. Higher rates of PD were found among alcohol-disordered individuals and those with Axis I disorders when compared with no-diagnosis and other Axis I-diagnosed control groups. The significance of PD among alcohol-disordered subjects was demonstrated further by a pattern of decrements in measures of adaptive functioning related to alcoholism, other Axis I, and Axis II diagnoses. Less than one-third of the alcohol-disordered subjects in this sample were without a coexisting Axis I or Axis II disorder.     

Examination of Cloninger''s Type I and Type II Alcoholism with a Sample of Men Alcoholics in Treatment

Cloninger's clinical method of classifying alcoholics into two groups (Types I and II) was examined with data obtained from 360 VA hospitalized male alcoholic patients. For operational criteria, the Cloninger clinical method of subtyping alcoholics employs age-of-onset of problem drinking and symptom-clusters supposedly associated with each subtype. Marked overlap was found between the symptom-clusters used to define the two subtypes. Ninety-one percent of the entire sample satisfied criteria for both symptom-clusters. Dividing the sample by early-onset (Type II, less than or equal to 25 years) and late-onset (Type I, greater than 26 years) alcoholism did not substantially reduce the overlap between symptom-clusters; i.e., 96% of the early-onset and 83% of the late-onset subgroups were positive for both symptom-clusters. Only 21 men (6%) could be classified when both age-of-onset and the type-appropriate symptom-cluster were used to separate patients. In hospital settings, at least, these findings suggest that the two-group clinical alcoholism typology proposed by Cloninger basically reflects the age-of-onset of problem drinking.     

Obsessive and Compulsive Characteristics of Craving for Alcohol in Alcohol Abuse and Dependence

The purpose of this study was to quantify the extent to which subjective ratings of craving for alcohol in the alcohol-abusing or dependent person (herein, alcoholic) correlate with measurable and specific characteristics of obsessions and compulsions. The Yale-Brown Obsessive Compulsive Scale modified to reflect obsessionality and compulsivity specifically related to heavy drinking (Y-BOCS-hd) was used for this purpose. Highly significant correlations were found in the alcoholic population (n = 62) between subjectively rated craving for alcoholic beverages and several of the Y-BOCS-hd questions regarding alcohol-related thoughts and drinking behavior. Additionally, mean craving scores were considerably greater in the alcoholic population than in the matched control population (n = 62). The data suggest that craving shares specific features in common with the obsessions of obsessive-compulsive disorder and that the existence of craving is dependent on the presence of obsessive thoughts about drinking. Positive correlations between craving and measures of compulsive drinking behavior also were found; compulsive drinking behavior, however, may reflect the consequences of craving rather than a fundamental characteristic of craving itself. The data show that despite difficulties in defining the term craving, it is clearly a phenomenon that is experienced or endorsed by most alcoholic subjects and is not by most persons who do not abuse alcohol.     

Hypothalamic-Pituitary-Thyroid (HPT) Axis in Chronic Alcoholism. I. HPT Axis in Chronic Alcoholics During Withdrawal and After 3 Weeks of Abstinence

Thyroxine (T₄), free T₄ (fT₄), triiodothyronine (T₃ free T₃ (fT₃), reverse T₃ (rT₃), thyrotropine (TSH), thyroxine binding globulin (TBG), and T₃ uptake were measured in 14 chronic alcoholics during withdrawal and after 21 days of abstinence. Results were compared with those of 16 healthy volunteers. During withdrawal, the fT₄ and fT₃ concentrations were subnormal, whereas the respective protein-bound fractions were normal. T₄, T₃, and TBG increased during the abstinence period, T₃ and TBG being significantly higher than in normals at the second measuring time. T₃ uptake values fell, but remained well within the normal range at both measuring times. During abstinence, the fT₃ levels remained significantly lower than in healthy subjects. rT₃ concentrations decreased, but not significantly. The TSH values were normal throughout. These results showed numerous abnormalities in the hypothal-amic-pituitary-thyroid axis in alcoholics, the reasons for which are as yet unclear. The following possible interpretations are suggested: 1. The abnormally low serum fT₃ and ff₄ levels during withdrawal might reflect an increase in tissue uptake. 2. The increases in T₄-and partty those in T₃-during abstinence seem to reflect increased binding by TBG, the level of which rose markedly for reasons as yet unknown. 3. If increases in TBG during abstinence are taken into account, the decreases in rT₃ concentrations may reach the level of statistical significance. These falls in rT₃ concentrations may reflect an increase in rT₃ metabolization (deiodination) in various tissues, including the CNS, leading to a reduction in serum rT₃ bioavail-ability. 4. Factors such as liver disease, protein caloric malnutrition, and “psychological stress” do not fully explain all these abnormalities. A direct effect of ethanol on intracellular thyroid hormone metabolism and/or function seems conceivable.     

Buspirone in the Treatment of Alcohol Dependence: A Placebo-Controlled Trial

A double-blind controlled study of the effects of buspirone on alcohol dependence and associated symptoms in ambulatory alcoholics showed a marked improvement in both treatment and control groups. However, significant differences in favor of the medication were observed in several psychopathological measures, but not in measures of alcohol consumption. Contrary to a majority of prior controlled trials of buspirone in alcoholics, subjects were not selected on the basis of comorbid generalized anxiety; rather, the study tested the hypothesis of a direct effect on craving and consumption, independent from an anxiolytic effect. This hypothesis was not confirmed.     

Prevalence of Alcohol Dependence and Abuse in General Practice

The aim of this study is to deliver representative epidemiological data about the prevalence of alcohol abuse and dependence in general practices in an urban area. In 12 general practices at Luebeck, a Northern German city with 220,000 inhabitants, a total of 929 patients (aged between 14 and 75 years) were screened using the CAGE and the Short Michigan Alcoholism Screening Test. If one of these screening questionnaires or the General Practitioners' assessment of the patient indicated an alcohol problem, the patient underwent a standardized diagnostic interview using the alcohol section of the Schedules for Clinical Assessment in Neuropsychiatry. The prevalence rates according to ICD-10 or DSM-III-R were 3.5% for alcohol abuse and 7.2% for alcohol dependence, the sex ratio was 1:2.8 (fema1e:male). These results are compared with previous findings, and general epidemiological implications of this study are discussed.     

Associations and Interactions Between SNPs in the Alcohol Metabolizing Genes and Alcoholism Phenotypes in European Americans

Background:  Alcohol dependence is a major cause of morbidity and mortality worldwide and has a strong familial component. Several linkage and association studies have identified chromosomal regions and/or genes that affect alcohol consumption, notably in genes involved in the 2-stage pathway of alcohol metabolism.
Methods:  Here, we use multiple regression models to test for associations and interactions between 2 alcohol-related phenotypes and SNPs in 17 genes involved in alcohol metabolism in a sample of 1,588 European American subjects.
Results:  The strongest evidence for association after correcting for multiple testing was between rs1229984, a nonsynonymous coding SNP in ADH1B, and DSM-IV symptom count ( p  =   0.0003). This SNP was also associated with maximum number of drinks in 24 hours ( p  =   0.0004). Each minor allele at this SNP predicts 45% fewer DSM-IV symptoms and 18% fewer max drinks. Another SNP in a splice site in ALDH1A1 (rs8187974) showed evidence for association with both phenotypes as well ( p  =   0.02 and 0.004, respectively), but neither association was significant after accounting for multiple testing. Minor alleles at this SNP predict greater alcohol consumption. In addition, pairwise interactions were observed between SNPs in several genes ( p  =   0.00002).
Conclusions:  We replicated the large effect of rs1229984 on alcohol behavior, and although not common (MAF = 4%), this polymorphism may be highly relevant from a public health perspective in European Americans. Another SNP, rs8187974, may also affect alcohol behavior but requires replication. Also, interactions between polymorphisms in genes involved in alcohol metabolism are likely determinants of the parameters that ultimately affect alcohol consumption.