Can We Subtype Alcoholism? A Latent Class Analysis of Data from Relatives of Alcoholics in a Multicenter Family Study of Alcoholism

We attempted to identify distinctive subtypes of alcoholics using latent class analysis with data from 2551 relatives of alcoholic pro-bands, all participants in the Collaborative Study of the Genetics of Alcoholism. Latent class analysis is a multivariate technique using cross-classified data to identify unobserved ("latent") classes that explain the relationships among observed variables. Data on 37 lifetime symptoms of alcohol dependence from 1360 female and 1191 male relatives were analyzed, with a 4 class solution selected as the best fitting among the 2 through 6 class solutions that were examined. We observed the following classes: class 1, nonproblem drinkers (39.6% male, 50% female); class 2, mild alcoholics (persistent desire to stop, tolerance, and blackouts) (31.8% male, 28.7% female); class 3, moderate alcoholics (social, health, and emotional problems) (18.9% male, 14.6% female); and class 4, severely alfected alcoholics (withdrawal, inability to stop drinking, craving, health, and emotional problems) (9.7% male, 6.7% female). There was little evidence for the construct of alcohol abuse; endorsement probabilities for abuse symptoms (e.g., arrests and DWIs) were very low for all classes, whereas hazardous use was common among men in class 1. In addition to those in class 3 and class 4, a majority of men in class 2 qualified for DSM-Ill-R alcohol dependence, suggesting a bimodal distribution of drinkers and alcoholics, with little nondependent problem drinking among men in this high-risk sample. We conclude that, in this sample, alcoholism is not differentiated by symptom profiles but rather lies on a continuum of severity, with the possible exception of withdrawal, which characterized only class 4 individuals.     

Cognitive Functioning, ASP, and Family History of Alcoholism in Young Men at Risk for Alcoholism

Previous research has suggested that individuals with a family history of alcoholism may have cognitive deficits that predate, and possibly predispose, to the onset of alcoholism. However, these deficiencies may result from other factors, e.g., comorbid psychopathology. The current study investigated the neuropsychological functioning of young adult males at high risk for alcohol abuse due to a family history of alcoholism (FH) and/or a personal history of antisocial personality disorder (ASP). A family history of alcoholism (FH+) alone was not associated with neuropsychological impairment. Subjects with ASP, however, exhibited some difficulty with higher level motor control and with verbal concept formation compared with nonASP subjects. No clear pattern of FH x ASP interaction was evident in the measures examined. These findings suggest that previous findings suggesting cognitive deficiencies in FH+ individuals may have been related to a failure to consider co-morbid ASP. The deficits exhibited by the ASP subjects may reflect both reduced inhibitory control and a deficiency in higher level verbal skills. These deficiencies may leave ASP individuals less capable of utilizing higher level language skills to regulate behavior.     

Pathways into Risk: Temperament and Behavior Problems in Three- to Five-Year-Old Sons of Alcoholics

Evidence suggests that a child with a difficult temperament, reared in an alcoholic family, is at high risk for the development of behavior problems that antedate the emergence of antisocial behavior, alcoholism, and coactive psychopathology. However, the causal linkage between difficult temperament and problem behavior in childhood, and antisociality and alcohol abuse in adulthood is far from certain, in part because few studies assess emergent behavior patterns in young children of alcoholics. In this study, we investigated the temperament-behavior problem relationship in 191 3- to 5-year-old boys, 149 of whom were being reared in high-risk alcoholic, low socioeconomic environments. Boys were classified as high in problem behavior or not based on standardized clinical cut-off scores for Total Behavior Problems from the Child Behavior Checklist. Results indicated that boys rated in the clinical range for total behavior problems exhibited more characteristics of difficult temperament than boys who were not rated in the clinical range. Parents of the boys in the clinical group had significantly more alcohol-related problems, higher levels of antisociality, and significantly lower levels of socioeconomic status, income, and education. Results are consistent with the supposition that the difficult temperament-behavior problem relationship flourishes in the context of an antisocial, alcoholic family environment.     

Adult Offspring of Alcoholic Women as Family History Informants

Eighteen years after their mothers had been hospitalized for alcoholism, adult offspring were asked if any of their 1st-degree relatives had ever had a drinking problem. Proband and informant characteristics that affect the validity of reports of maternal drinking problems given by adult offspring of alcoholic women were identified. A history of alcohol-related medical problems in the mother was associated with reporting maternal alcoholism. Being African-American, having a history of suicide attempts in the mother, and having a good maternal posttreatment outcome were associated with false-negative reports. Adding multiple offspring informants increased sensitivity to 86%. Female alcoholic offspring tended to underreport maternal alcoholism.     

Alcohol Schema Acquisition in Preschoolers: Differences Between Children of Alcoholics and Children of Nonalcoholics

Cognitive schemas provide the structure within which children organize their knowledge and beliefs about the use of alcohol. The development of schemas about alcohol should be affected both by age and parental patterns of alcohol use. We examined differences in alcohol schema development among 139 male children of alcoholics (COAs) and 82 controls [children of nonalcoholics (NCOAs)] utilizing the Appropriate Beverage Task as an indicator of these processes. Overall, the vast majority of the sample identified at least one alcoholic beverage from photographs, even at age 3. COAs were more likely to identify at least one alcoholic beverage. With age controlled, COAs were better able to identify specific alcoholic beverages and correctly identified a larger number of alcoholic beverages. There was a trend for these children of alcoholic men to attribute more alcoholic beverage use to male adults than NCOAs. Moreover, differences in these children's attributions of alcoholic consummatory behavior were predicted by their parents' current consumption levels. Results provide evidence that alcohol schemas are detectable in early childhood and are more common in children from alcoholic homes. Discussion focuses on the potential relevance of these risk attributes to the development of more fully formed alcohol expectancies and to the later emergence of alcohol-related difficulty.     

Gender‐Related Influences of Parental Alcoholism on the Prevalence of Psychiatric Illnesses: Analysis of the National Epidemiologic Survey on Alcohol and Related Conditions

Background: Offspring of individuals with alcoholism are at increased risk for psychiatric illness, but the effects of gender on this risk are not well known. In this study, we tested the hypothesis that the gender of the parent with alcoholism and the gender of offspring affect the association between parental alcoholism and offspring psychiatric illness. Method: We analyzed the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) data to examine the gender‐specific prevalence of axis I and axis II disorders in 23,006 male and 17,368 female respondents with and without a history of paternal or maternal alcoholism. Adjusted odds ratios were calculated for the disorders based on gender and presence of maternal or paternal alcoholism. Results: Maternal or paternal alcoholism was associated with a higher prevalence of every disorder examined, regardless of the gender of offspring. Gender‐related differences in prevalences were present in nearly all examined disorders, and the association between parental alcoholism and offspring psychiatric disorders was significantly different in men and women. These differences included stronger associations in female offspring of men with alcoholism (alcohol abuse without dependence); in female offspring of women with alcoholism (mania, nicotine dependence, alcohol abuse, and schizoid personality disorder); in male offspring of men with alcoholism (mania); and in male offspring of women with alcoholism (panic disorder). Conclusions: Interactions between gender and parental alcoholism were specific to certain disorders but varied in their effects, and in general female children of women with alcoholism appear at greatest risk for adult psychopathology.     

A Preliminary Study of Acute Responses to Clamped Alcohol Concentration and Family History of Alcoholism

BACKGROUND: The clamping method of alcohol administration was combined with a battery of dependent measures of frontal lobe brain function, and a novel index of acute adaptation, in a preliminary study in order to explore the paradigm's sensitivity to a familial history of alcoholism (FHA). METHODS: Ten family history-positive (FHP) and 10 family history-negative (FHN) adult social drinkers of both genders underwent alcohol clamping. Twenty minutes after the start of an intravenous infusion of alcohol, the breath alcohol concentration was clamped at a target of 60+/-5 mg/dl for 150 min. Initial and adaptive responses to alcohol were assessed using scalar indices of change. One index assessed initial improvements or impairments in brain function after alcohol. The other index assessed acute adaptation (tolerance or sensitization) to alcohol while the brain's exposure to alcohol was held constant. The battery of dependent measures included subjective perceptions, neuropsychological tests, saccadic eye-movement tasks, and event-related potential (ERP) tasks. Effect sizes for FHA were estimated for 10 dependent variables that showed adequate baseline test-retest reliability (r>0.6). RESULTS: FHP subjects showed less intense initial responses to alcohol in subjective perceptions, but greater changes in the latency of volitional saccades and ERP P3 components than did the FHN controls. FHP subjects generally showed greater acute tolerance to alcohol than did controls, who showed more instances of acute sensitization at this moderate breath alcohol concentration. Effect sizes for FHA exceeded 0.4 in more than half of the indices. CONCLUSIONS: The BrAC clamping paradigm assesses initial and adaptive responses of a battery of behavioral and electrophysiological measures of frontal lobe function to ethanol that appear both reliable and sensitive to FHA.     

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.     

Effects of Abstinence and Family History for Alcoholism on Platelet Adenylyl Cyclase Activity

Platelet adenylyl cyclase (AC) activity was measured in 32 alcohol-dependent subjects and 27 control subjects who were categorized as either family history-positive (FHP) or family history-negative (FHN) for alcoholism. The interview and blood sample collections were performed shortly after cessation of heavy drinking in the alcoholic group, and repeat blood samples were obtained at the end of the first and second weeks of monitored abstinence. Control subjects received the same interview and provided blood samples at the time of the interview. When subjects were not segregated for FHP or FHN status, there were no statistically significant differences in basal, cesium fluoride (CsF)-, orforskolin-stimulated mean AC activities between the controls and the alcoholics, at study entry or with 1 or 2 weeks of abstinence. On the other hand, over the 2-week course of sobriety from heavy drinking, the CsF-stimulated AC activity of FHP alcohol-dependent subjects decreased significantly (p = 0.03). FHP alcohol-dependent subjects after 2 weeks of sobriety had significantly lower mean CsF-stimulated AC activity than FHN controls (p = 0.04), whereas the FHN alcoholic subjects' CsF-stimulated AC activity did not differ significantly from FHN controls at this point in time. When all subjects were pooled and then categorized as either FHP or FHN, there was a significant difference in mean CsF-stimulated AC activity (p = 0.02) between the FHP and FHN subject groups. Genetic factors and abstinence appear to have roles in determining low platelet AC activity in alcoholic and nonalcoholic subjects. CsF-stimulated platelet AC activity, in particular, appears to act as a trait marker for a genetic vulnerability to developing alcoholism, but recent heavy drinking in male alcoholics is a factor that can mask differences between FHP and FHN subjects.     

Analgesic Effects of Ethanol Are Influenced by Family History of Alcoholism and Neuroticism

Background: Although personality factors and family history of substance abuse influence how individuals experience pain and respond to analgesics, the combined effects of those factors have not been extensively studied. The objective of this study was to consider the possible role of personality trait of neuroticism and family history of alcoholism on the experience of pain and their role in the analgesic response to an ethanol challenge. Methods: Forty‐eight healthy subjects participated in this study; thirty‐one had a positive family history of alcoholism (FHP), seventeen had a negative family history of alcoholism (FHN). They were also categorized based on their neuroticism (N) scores (low N = 28, and high N = 20). This was a double‐blind, placebo‐controlled, randomized, within‐subject design study of intravenous administration of three doses of ethanol. The testing consisted of 3 separate test days scheduled at least 3 days apart. Test days included a placebo day (saline solution), low‐exposure ethanol day (targeted breathalyzer = 0.040 g/dl), and high‐exposure ethanol day (targeted breathalyzer = 0.100 g/dl). Noxious electrical stimulation and pain assessments were performed prior to start of infusion and at the 60‐minute infusion mark. Results: The analgesic effect of ethanol was mediated by an interaction between the personality trait of neuroticism and family history. Individuals with family history of alcoholism and high N scores reported significantly more analgesia on low dose of ethanol than those with low N scores. There was no difference in the analgesic response to ethanol among FHNs with low and high N scores. Conclusion: These findings support the conclusion that neuroticism and family history of alcoholism both influence the analgesic response of alcohol. Individuals with high N scores and FHP have the strongest response to ethanol analgesia particularly on the low exposure to alcohol.     

Family History of Alcoholism and the Mediation of Alcohol Intake by Catalase: Further Evidence for Catalase as a Marker of the Propensity to Ingest Alcohol

Earlier studies have suggested that catalase activity (CA) may represent a biological marker of alcohol intake in animals and in humans. An initial study was designed to rule out the possibility that CA is induced as a function of acute alcohol intake. Subjects ( n = 80) were presented with either an alcohol (0.5 g/kg of body weight) or control solution, and asked to provide four 100-μl blood samples at 0.0, 0.5, 2.0, and 24.0 hr. Results showed no differences in CA between individuals who had received alcohol, and controls, even when the effects of previous drinking history were covaried out. This lack of effect of acute alcohol intake on the possible induction of CA further supported the notion that CA may be a viable marker of alcohol intake, rather than the converse. In the second study, the relation between CA and alcohol intake was investigated in individuals with a family history (FH) of alcoholism (FH+), and in those without a family history of alcoholism (FH-). Subjects ( n = 607) completed the Michigan Alcoholism Screening Questionnaire, the MacAndrew Scale, and the Concordia University Alcohol Screening Questionnaire; answered questions concerning their FH for alcoholism; and provided a 100-μl blood sample. Results showed that FH+ individuals had higher mean CA compared with FH- individuals. When individuals with FH+ were compared with those with FH-, differences in the pattern of relation between CA and alcohol intake were observed. Although a significant relation between CA and alcohol intake was obtained for both FH- and FH+ individuals, this relation was significantly higher ( p < 0.001) for individuals with FH+. Results from a multiple regression analyses suggested that CA in FH+ individuals made the highest single contribution to the variance, even after accounting for several additional variables. These results support the contention that CA may be a biological marker of the propensity of FH+ individuals to consume alcohol.     

Alcoholics Anonymous and hazardously drinking women returning to the community after incarceration: predictors of attendance and outcome

Background: The number of women incarcerated within the United States has risen dramatically in recent decades, and high rates of alcohol problems are evident among this population. Although little is known about the patterns of help utilization and efficacy for alcohol problems, preliminary evidence suggests that Alcoholics Anonymous (AA) is a widely available resource for this population. Methods: Data were collected as part of a study evaluating the effect of a brief intervention to reduce alcohol use among hazardously drinking (i.e., score of 8 or above on the Alcohol Use Disorders Identification Test or 4 or more drinks at a time on at least 3 days in prior 3 months) incarcerated women. The current study characterized demographic, clinical, and previous AA attendance variables associated with AA attendance in the 6 months following incarceration. Associations between frequency of AA attendance and drinking outcomes following incarceration were also evaluated. Results: Among the 224 participants who provided data about AA attendance, 54% reported some AA attendance during the follow‐up assessment period. AA attendance in the year prior to study entry (OR = 4.02; 95% CI: 3.32 to 4.71) and greater baseline consequences of alcohol use (OR = 2.09; 95% CI: 1.73 to 2.44) were associated with increased odds of higher frequency of AA attendance following incarceration. Weekly or greater AA attendance was associated with reductions in negative drinking consequences (B = ?0.45; p < 0.01) and frequency of drinking days (B = ?0.28; p < 0.01) following incarceration. Conclusions: Findings from this study suggest that AA is frequently utilized by hazardously drinking women following incarceration. Alcohol outcomes may be enhanced by AA attendance at a weekly or greater frequency is associated with better alcohol outcomes relative to lower levels of AA attendance. Evaluation of clinical guidelines for prescribing AA attendance for incarcerated women remains a task for future research.     

Adherence to Recovery Practices Prescribed by Alcoholics Anonymous: Benefits to Sustained Abstinence and Subjective Quality of Life

In a British cultural context, we tested the idea that physical abstinence and psycho-existential well-being during the aftercare period of recovery may be enhanced by higher levels of overall compliance with Alcoholics Anonymous (AA)-prescribed practices. We also examined whether enactment of certain types of AA-sanctioned practices might carry greater (or unique) therapeutic benefits relative to engagement in other ingredients of AA. Former residents (n = 76) of a Minnesota Model treatment program (in England) were assessed 2 years after being discharged. Higher levels of overall adherence tended also to be associated with greater abstinence, lower depression, and a stronger conviction that life has meaning and purpose. Microanalysis of discreet types of AA involvement showed formal completion of Steps 4 and 5 (done as a pair with a sponsor) had a robust salutary effect, being related to abstinence and better emotional and existential well-being. In addition, participation in Step 11 (praying/meditating) and having an AA sponsor were both associated with a broad spectrum of apparent benefits. Practitioners might consider implementing motivational interventions designed to facilitate greater client willingness to adhere more closely to the AA style of living. Results that identified especially potent facets of the AA lifestyle suggest counselors concerned with “high-quality abstinence” may wish to tailor such interventions so as to selectively target active ingredients.     

Family History of Alcoholism and Childhood Adversity: Joint Effects on Alcohol Consumption and Dependence

Empirical studies provide substantial evidence that having a family history of alcoholism increases the risk of developing alcohol dependence; however, some of this effect may be caused by nonspecific childhood socioeconomic adversity common in families with an alcohol-dependent parent. In this study, we examine joint effects of family history and childhood adversity within a sample of 509 men and 217 women over age 40. The measures analyzed were included in routine screening assessments for participants in various studies at the University of Michigan Alcohol Research Center. About 60% of the men and 45% of the women were alcohol-dependent. About 30% reported an alcoholic parent. Degree of family history affected drinking behavior for both men and women. There were also environmental effects on the same measures for both men and women. Childhood socioeconomic adversity was reported more frequently by participants with an alcoholic parent, but adversity effects were also shown for those with a negative family history. The risk of alcohol dependence was additively increased by a positive family history and childhood socioeconomic adversity. The environmental effects identified in this study are promising evidence for nonspecific factors that moderate family history risk for development of alcohol problems.     

Delay Discounting Behavior and White Matter Microstructure Abnormalities in Youth With a Family History of Alcoholism

Background: Youth with family history of alcohol abuse have a greater risk of developing an alcohol use disorder (AUD). Brain and behavior differences may underlie this increased vulnerability. The current study examined delay discounting behavior and white matter microstructure in youth at high risk for alcohol abuse, as determined by a family history of alcoholism (FH+), and youth without such family history (FH?). Methods: Thirty‐three healthy youth (FH+ = 15, FH? = 18), ages 11 to 15 years, completed a delay discounting task and underwent diffusion tensor imaging. Tract‐based spatial statistics ( Smith et al., 2006 ), as well as follow‐up region‐of‐interest analyses, were performed to compare fractional anisotropy (FA) between FH+ and FH? youth. Results: FH+ youth showed a trend toward increased discounting behavior and had significantly slower reaction times (RTs) on the delay discounting paradigm compared to FH? youth. Group differences in FA were seen in several white matter tracts. Furthermore, lower FA in the left inferior longitudinal fasciculus and the right optic radiation statistically mediated the relationship between FH status and slower RTs on the delay discounting task. Conclusions: Youth with a family history of substance abuse have disrupted white matter microstructure, which likely contributes to less efficient cortical processing and may act as an intrinsic risk factor contributing to an increased susceptibility of developing AUD. In addition, FHP youth showed a trend toward greater impulsive decision making, possibly representing an inherent personal characteristic that may facilitate substance use onset and abuse in high‐risk youth.     

Comparison of Direct Interview and Family History Diagnoses of Alcohol Dependence

Using data from The Collaborative Study on the Genetics of Alcoholism, we compare direct interview diagnoses of alcohol dependence to those obtained by history from family members. Using a requirement of three or more positive implications by history, the specificity, sensitivity, and positive predictive values are 98%, 39%, and 45%, respectively.
A logistic analysis found the gender of the relative and alcoholism in the informant to be significant, but not the gender of the informant. The partial odds ratio of a diagnosis at interview associated with a positive family history diagnosis was 13.6. The relationship between the informant and relative was significant, with negative reports from an offspring or mate more influential than a negative report from a parent or second-degree relative.
We derived a recursive equation to combine a variable number of family history reports, wherein the probabilities associated with a single report are computed from the logistic analysis. This permits the use of family history information both as a proxy for an uninterviewed relative, as well as a second source of information to be used in the analysis of genetic family data.     

The University of California, San Francisco Family Alcoholism Study. I. Design, methods, and demographics

BACKGROUND: The University of California, San Francisco (UCSF) Family Alcoholism Study is a project designed to identify genetic loci that influence susceptibility to alcohol dependence and related phenotypes. Evidence supports a substantial genetic contribution to alcoholism susceptibility. However, the genetic epidemiology of alcoholism is complex, and its clinical manifestation is heterogeneous, making phenotype definition and demonstration of linkage difficult. Despite these challenges, some progress has been made toward identifying genes. METHODS: The UCSF Family Alcoholism Study used a small family design, focusing primarily on sibling pairs and parent-child trios for linkage and association studies. Alcoholism-related phenotypes were assessed through interview and self-report questionnaires, with a focus on unidimensional and subphenotypical traits. Data-driven approaches to determining the most promising phenotypes for genetic analysis are being used. Both genome-wide scan and candidate gene approaches were used. RESULTS: The study enrolled 2154 individuals from 970 families from December 1995 through January 2003. Test-retest and interrater reliability for clinical data are very good, and power estimates suggest that this study will have adequate power by linkage analysis to detect loci with moderate effects. Design, methods, and sample demographics of the UCSF Family Study are presented, along with intrafamilial correlations for primary diagnostic phenotypes. CONCLUSIONS: Plans for genetic analysis, novel approaches to phenotype refinement, and the implications of ascertainment bias for heritability estimates are discussed.