Heterogeneity in the inheritance of alcoholism. A study of male and female twins.

Genetic influence on risk for alcoholism was examined in a US treatment sample of 50 monozygotic (MZ) and 64 dizygotic (DZ) male and 31 MZ and 24 DZ female same-sex twin pairs. For the DSM-III composite diagnosis of Alcohol Abuse and/or Dependence, statistically significant MZ/DZ differences in concordance were found with male, but not female, twins. For specific diagnoses, MZ/DZ differences were found in male subjects for both Alcohol Abuse and Alcohol Dependence, while MZ/DZ differences in female subjects were found only for Alcohol Dependence. The male MZ/DZ concordance difference for composite diagnosis but not for Alcohol Dependence could be accounted for statistically by differences in age of onset between MZ and DZ probands. As with alcohol, differences in MZ/DZ concordance were found for DSM-III composite diagnoses of Other Substance Abuse and/or Dependence with male, but not female, twins. Using Epidemiological Catchment Area data to estimate the population base rates of both alcohol and other substance use disorders allowed for heritability analyses that showed genetic factors to have only a modest influence on overall risk in both sexes (heritability estimates of approximately 0.35 for male subjects and 0.24 for female subjects). However, evidence for heterogeneity in the pattern of inheritance was also found, suggesting forms of alcoholism that may be moderately to highly heritable.

The Composite International Diagnostic Interview. An epidemiologic Instrument suitable for use in conjunction with different diagnostic systems and in different cultures.

The Composite International Diagnostic Interview (CIDI), written at the request of the World Health Organization/US Alcohol, Drug Abuse, and Mental Health Administration Task Force on Psychiatric Assessment Instruments, combines questions from the Diagnostic Interview Schedule with questions designed to elicit Present State Examination items. It is fully structured to allow administration by lay interviewers and scoring of diagnoses by computer. A special Substance Abuse Module covers tobacco, alcohol, and other drug abuse in considerable detail, allowing the assessment of the quality and severity of dependence and its course. This article describes the design and development of the CIDI and the current field testing of a slightly reduced "core" version. The field test is being conducted in 19 centers around the world to assess the interviews' reliability and its acceptability to clinicians and the general populace in different cultures and to provide data on which to base revisions that may be found necessary. In addition, questions to assess International Classification of Diseases, ninth revision, and the revised DSM-III diagnoses are being written. If all goes well, the CIDI will allow investigators reliably to assess mental disorders according to the most widely accepted nomenclatures in many different populations and cultures.

Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers.

Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction fragment length polymorphism of the D2 dopamine receptor gene, according to four of six studies that examined alcoholics and controls. The current study examines whether the association observed in alcoholism might extend to other addictive substances by examining D2 dopamine receptor Taq I A and B restriction fragment length polymorphisms in polysubstance users and controls free of significant substance use. We hypothesized a stronger association for the B1 restriction fragment length polymorphism since it lies closer to dopamine receptor protein coding and 5' regulatory regions. Heavy polysubstance users and subjects with DSM-III-R psychoactive substance use diagnoses displayed significantly higher Taq I B1 frequencies than control subjects; Taq I A1 results for these comparisons were less robust. These results are consistent with a role for a D2 dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability.

HIV risk factors among injecting drug users in five US cities.

OBJECTIVES: To examine factors associated with HIV infection in injecting drug users (IDU), the independent and interactive effects of potential risk factors, and geographic differences in risk factors. METHODS: IDU entering methadone treatment in New York City, Asbury Park and Trenton in New Jersey, Baltimore and Chicago between February 1987 and December 1991 were interviewed using a standard questionnaire and tested for HIV antibodies (n = 4584). Associations of HIV serostatus with race/ethnicity, other demographic characteristics, and injecting and sexual risk behaviors were assessed by logistic regression analyses. RESULTS: African Americans were at increased risk for HIV in four of the five cities, and Puerto Ricans in two cities. Injection in shooting galleries and 'speedball' injection emerged as behavioral variables highly associated with HIV, although interaction of these variables indicates that each variable contributes to HIV risk only in the absence of the other behavior. CONCLUSIONS: Geographic differences in HIV risk factors and the interaction of 'speedball' and shooting gallery use suggest that multiple HIV risk models are needed that reflect seroprevalence rates, variation in risk behaviors, and the social context of risk behaviors. Increased risk among racial/ethnic minorities independent of risk behaviors, suggests the need to examine further potential social and environmental factors, such as the social networks in which injecting and sexual behaviors occur, HIV seroprevalence within these networks, and the locales in which risk behaviors occur.

Genetic analysis of diagnostic systems of alcoholism in males.

BACKGROUND: Research into genes involved in alcoholism could benefit from use of diagnostic systems most sensitive to detecting genetic influences. In this study, heritable influences were estimated in a single twin sample with commonly used criteria for alcoholism. METHODS: Male twin probands ascertained through alcohol and drug abuse treatment programs and their same-sex cotwins (54 monozygotic and 65 dizygotic pairs) were diagnosed independently by DSM-III (alcohol dependence and alcohol abuse and/or dependence), Feighner (probable and definite alcoholism), and Cloninger (type 1 and type 2 alcoholism) systems. Using univariate structural equation modeling, heritability was estimated for each diagnostic system. RESULTS: The highest heritability estimates were obtained for Feighner probable alcoholism (h2 = .63), Cloninger type 2 alcoholism (h2 = .54), and DSM-III alcohol dependence (h2 = .52). CONCLUSIONS: Certain diagnostic systems appear to have greater sensitivity for detecting genetic influence and may therefore be more appropriate for use in molecular genetic studies attempting to find genes for alcoholism.

Posttreatment depression in an alcohol and drug abuse population.

The prevalence and extent of relapse and the prevalence and severity of depressive symptoms were measured cross-sectionally in a group of alcohol and drug abusers (N = 842) at 1, 6, or 12 months after their discharge from alcohol or drug abuse treatment. The rate and severity of depressive symptoms for subjects who did not relapse were no higher than those found among the general population. However, among subjects who relapsed, the rate and severity of depressive symptoms were higher than those found in the general population. Women were more depressed than men after treatment, but the ratio of depressed women to men was no higher than that found in the general population.

Introduction of HIV infection among intravenous drug abusers in low prevalence areas.

To explore the introduction of human immunodeficiency virus (HIV) infection into intravenous drug abusing populations, risk behaviors of 1,154 intravenous drug abusers (IVDAs) in four U.S. cities with low prevalence of IVDA/HIV infection (0.9-13.0%) were examined. Seropositive subjects (N = 54) were compared with demographically matched seronegative controls regarding drug use practices, homosexual contact, blood transfusions, risk behaviors while traveling or living in high prevalence areas, and acquaintance with persons with AIDS. With the exception of needle sharing with homosexual/bisexual males, no differences in risk behaviors were found between seropositive subjects and matched seronegatives. Seropositives were substantially more likely than matched seronegatives to report having shared a needle with a homosexual or bisexual male, suggesting that needle sharing between homosexual/bisexual IVDAs and heterosexual IVDAs may be an important means by which HIV is introduced among heterosexual IVDAs in low prevalence areas.

HIV infection and AIDS risk behaviors among intravenous drug users entering methadone treatment in selected U.S. cities.

To assess trends in HIV infection and AIDS risk behaviors among intravenous drug users (IVDUs), a series of nonblinded point-prevalence surveys was conducted with admissions to methadone treatment in seven areas, including New York City; Trenton and Asbury Park, New Jersey; Baltimore; Chicago; San Antonio, Texas; and Los Angeles County between February and December 1987 (n = 713), January and June 1988 (n = 1,089), July and December 1988 (n = 932), and January and June 1989 (n = 1,110). Over the 2-year period, significant changes in HIV seropositivity levels were found in only one of the seven cities (Chicago, with levels increasing from 8.4 to 14.7%). High levels of AIDS risk behaviors (frequency of injection, needle sharing, needle cleaning, and use of shooting galleries) were found in all cities. Comparisons of trends in recent risk behaviors (past year) within cities suggest that relatively little reduction in AIDS risk behaviors had occurred during the study.

Effects of clorazepate, diazepam, lorazepam, and placebo on human memory.

Healthy adults (N = 10) were given oral doses of lorazepam (1 and 2 mg), diazepam (5 and 10 mg), clorazepate (7.5 and 15 mg), or placebo and tested 30, 60, 90, and 120 minutes later on a word-recall memory task. All subjects received each drug dose once and placebo twice in randomized order at weekly intervals. Testing was double-blind. Lorazepam was found to have a significantly greater effect on memory than placebo. Diazepam and clorazepate did not differ significantly from placebo in their effect on word recall. High doses of lorazepam produced more pronounced memory effects than did low doses; neither diazepam nor clorazepate was found to exert a dose-related effect on memory.

Reaction time performance as a function of cigarette smoking procedure.

Laboratory studies examining the effects of cigarette smoking on behaviour have routinely employed a variety of standardized smoking procedures. This study examined whether reaction time performance after smoking varied as a function of the cigarette smoking procedure employed. Twelve regular smokers were tested on a reaction time task after smoking on three different occasions. In each session, they smoked by one of the three following procedures: (1) ad libitum smoking of their own cigarette; (2) ad libitum smoking of a standard cigarette; (3) smoking a standard cigarette with a prescribed puff pattern. The results show that reaction time performance was significantly faster after smoking under the latter two conditions relative to the subjects' performance after ad libitum smoking of their own cigarette. These findings illustrate that experimental requirements which are commonly imposed upon subjects may affect the results obtained.

Tobacco withdrawal symptoms: an experimental analysis.

This study was a prospective examination of tobacco withdrawal symptoms in a controlled environment. Smokers (N = 27) were hospitalized for a 7-day period during which a battery of tests was administered. Smokers were assigned to either an experimental group (N = 20) or a control group (N = 7). Subjects in the experimental group smoked ad libitum for a 3-day baseline period and then underwent 4 days of tobacco deprivation. Subjects in the control group continued to smoke ad libitum throughout the study. Of the 37 measures of tobacco withdrawal employed in this study, nine showed significant changes following tobacco deprivation. These changes include decreased heart rate and increased caloric intake, weight, craving for tobacco, confusion, depression-dejection, number of awakenings, duration of awakenings, and increased poor concentrations as observed by others.

Effect of nicotine on the tobacco withdrawal syndrome.

This study tested the ability of nicotine to alleviate the tobacco withdrawal syndrome. Signs and symptoms of tobacco withdrawal were measured in 100 smokers who fulfilled DSM-III criteria for tobacco dependence and a past history of tobacco withdrawal. After 2 evenings of baseline measurement, subjects were randomly assigned to receive either nicotine or placebo gum in a double blind manner. Subjects then stopped smoking, chewed gum freely, and returned on the 1st, 2nd, and 4th evenings of abstinence for further measurement. Nicotine reduced the increase in irritability, anxiety, difficulty concentrating, restlessness, impatience, and somatic complaints that subjects reported after cessation. Reductions in these withdrawal symptoms by nicotine were confirmed by ratings of significant others and by subjects' scores on the Profile of Mood States. Nicotine did not reduce the increases in cigarette craving, hunger, eating, insomnia, tremulousness , or supine heart rate after cessation. The effects of nicotine occurred immediately and persisted throughout the study. Although many subjects correctly identified their drug group, the efficacy of the gum was independent of subjects' identifications of drug. The relief of tobacco withdrawal by nicotine gum suggests that the tobacco withdrawal syndrome is caused, in part, by nicotine deprivation.

The relationship between chronic ethanol exposure and cigarette smoking in the laboratory and the natural environment.

Few studies have examined the association between ethanol use and cigarette smoking topography. In particular, no study has objectively investigated the relationship between chronic ethanol exposure and cigarette smoking. The aim of this study was to quantify the relationship between cigarette smoking and past and current ethanol use. Male and female cigarette smokers (n = 77) between the ages of 30 and 65 years were recruited and grouped as a function of their past and current ethanol use. Group 1 (n = 18) included subjects who were ethanol abstinent for the 3 months prior to the study and had no history of alcohol abuse (as defined by DSM-III criteria). Group 2 (n = 19) included subjects who were current regular ethanol users and had no history of alcohol abuse. Group 3 (n = 20) included subjects who were ethanol abstinent and had a history of alcohol abuse. Group 4 (n = 20) included current regular ethanol users with a history of alcohol abuse. A history of alcohol abuse was associated with an intensified pattern of cigarette smoking. Significant differences were observed for total daily smoke exposure, cigarette number, puff number, total puff and inhalation volume, and the nicotine, tar and carbon monoxide yields of the cigarettes smoked. Increased expired-air carbon monoxide and serum cotinine levels were also observed. Current ethanol use was not associated with an increased cigarette smoking pattern. These data suggest that alcohol abusers are at greater risk of contracting cigarette-related pathology.

Sex and age effects on the inheritance of alcohol problems: a twin study.

Male monozygotic cotwins of probands with Alcohol Abuse-Dependence (n = 85) were more likely than male same-sex dizygotic cotwins (n = 96) to report alcohol, drug, and conduct disorder problems. For women, rates of problem behavior did not differ between monozygotic (n = 44) and same-sex dizygotic (n = 43) cotwins. Opposite-sex dizygotic twin data (n = 88) revealed significant cross-sex transmission; alcohol problems were greatest among male cotwins of female probands. For men, proportion of liability variance associated with additive genetic factors was significantly greater when proband had an early (h2 = .73 +/- .18) rather than late (h2 = .30 +/- .26) age of onset. For women, heritability did not vary as a function of proband's age of onset, and the pooled estimate suggested little genetic influence (h2 = .00, SE not computable). Findings suggest that genetic influences may be substantial only in the etiology of early-onset male alcoholism.

Substance use risk factors for HIV infection.

The focus on reducing needle sharing by IVDUs as an HIV-control strategy is well supported by epidemiologic data. Because of this emphasis, however, the role of other HIV risk factors in drug use is sometimes overlooked. Although needle sharing by IVDUs undoubtedly will continue to be one of the greatest risk factor for HIV infection in drug users, other risk factors in HIV infection also are associated with drug use and may contribute significantly to the spread of HIV infection. It is clear that the role of drug use in AIDS is not limited to needle sharing by IVDUs. HIV infection can be transmitted by any type of needle use. Nonintravenous drugs (e.g., crack) and other risk factors (e.g., unprotected sex) also may play a role in the spread of HIV infection. Because of its dependence potential, crack may come to play a major role in HIV transmission, primarily because of its link to unprotected sexual behavior.

Craving: consensus of status and agenda for future research.

The term craving is used frequently in relationship to drug abuse and its treatment but there is disagreement over its definition and role. In February 1991, a meeting of experts from several disciplines, sponsored by the Addiction Research Center (ARC) of the National Institute on Drug Abuse, was convened with the goal of reaching consensus about the importance of craving and to suggest a future research program. The participants agreed that craving is a subjective state in humans that is associated with drug dependence but little is known about its determinants, relationship to drug taking, and measurement. To advance our knowledge, a substantial research program is required. The outcome of this research effort could have important consequences for increasing our understanding of the determinants of drug abuse.

Post-treatment depressive symptoms and relapse to drug use in different age groups of an alcohol and other drug abuse population.

The prevalence of relapse to alcohol or other drug use and prevalence and severity of depressive symptoms were measured cross-sectionally in different age groups of alcohol and drug abusers at one, six, and twelve months post-discharge. Relapse rates increased over time since discharge for all age groups (17 - 29, 30 - 39, 40 - 49, and 50+ years). However, no differential effect of age was found on relapse rates at each of the three post-discharge intervals. Rates of depressive symptoms increased over time since discharge only for the youngest age group. Mean depressive symptom scores increased over time since discharge only for the 17 - 29 and 50+ age groups. There were significant differences between age groups in rates of depressive symptoms at six and twelve months post-discharge and on mean depressive symptom scores at one, six and twelve months post-discharge and on mean depressive symptom scores at one, six and twelve months post-discharge. In addition, for abstinent and for relapsed subjects, there were significant differences between age groups in rates of depressive symptoms and mean depressive symptom scores. Higher rates of depressive symptoms were found in relapsed than abstinent subjects at the younger ages (17 - 29 and 30 - 39 years), with mean depressive symptom scores being higher for relapsed than abstinent subjects in all age groups.

Common genetic mechanisms in alcohol, drug, and mental disorder comorbidity.

Comorbid drug and mental disorders were assessed in 63 monozygotic (MZ) and 67 dizygotic (DZ) twin pairs. DSM-III alcohol dependence was heritable in males when probands had a comorbid DSM-III drug or mental disorder but not when probands had only alcohol dependence. For males, significantly higher cross-MZ than cross-DZ correlations were found between alcohol dependence in probands and certain mental and drug disorders in cotwins. In contrast, females showed higher within-twin than cross-MZ correlations and similar cross-MZ and cross-DZ correlations between alcohol dependence and all mental and drug disorders. These results suggest comorbidity between alcohol and certain drug and mental disorders in males in epidemiological surveys may be due in part to genetic influences.

Genetic influences in antisocial personality and drug use disorders.

While an association between antisocial personality disorder (APD) and substance use disorder (SUD) has been frequently observed, the causes of the comorbidity remain unclear. Adoption and twin studies have found evidence of both genetic and environmental influences in APD and SUD. Therefore, comorbidity between APD and SUD may be the result of shared genetic influences, shared environmental influences, or a combination of the two. However, only a limited number of adoption and twin studies have addressed this issue and the results have not been conclusive. In future studies, a distinction should be made between alcohol and drug abuse and between juvenile and adult APD symptoms. Twin samples of adequate size would allow use of structural equation analytical methods for estimation of the relative magnitude of genetic and environmental influences shared between the two conditions, as well as influences contributing to each specifically. Results would be highly relevant for the clinical setting as well as for efforts to identify the genes involved in either trait.

Genetic and environmental influences on drug use and abuse/dependence in male and female twins.

Twins were recruited through alcohol and drug treatment programs. With structural equation modeling, genetic and environmental estimates were obtained for use and DSM-III abuse/dependence of sedatives, opioids, cocaine, stimulants, and cannabis as well as any illicit drug. Analyses were conducted separately for males and females. Models included thresholds based on population prevalence of use or abuse/dependence and ever having been in treatment. Genetic influences were found for most measures. They were generally stronger for males than females and for clinical diagnoses of abuse/dependence compared to use. Common environmental influences played a greater role in use than abuse/dependence.