Familial transmission of alcoholism among nonalcoholics and mild, severe, and dyssocial subtypes of alcoholism.

BACKGROUND: In the field of alcohol studies, there are many typologies attempting to reduce the heterogeneity of expression of this complex disorder to better understand its natural history and etiology. However, few typologies have included empirical assessment of the degree of familial liability. To the extent there is variability in genetic vulnerability to alcoholism, inclusion of measures of this variability in proposed typologies is important to their validity and utility. We test whether the mild, severe, and dyssocial typology distinguished cases of alcohol dependence with high familial liability from those with low familial liability to alcoholism. METHODS: Data came from the National Longitudinal Alcohol Epidemiologic Survey-1992, a household probability sample representative of those 18 years of age and older in the contiguous US Response rate was 92%. Only whites were included here because the typology under study has been successfully applied to this race/ethnic group only. The total number of respondents were 32,447 and included 13,825 men and 18,622 women. Identification of a biological relative as alcoholic was based on the proband's report. All analyses were weighted to adjust for sampling under a multistage stratified design. RESULTS: Familial density of alcoholism (number of alcoholics/number of adult family members) substantially differed by proband alcohol dependence status for both men and women (male probands-nonalcoholics 7%, mild 13%, severe 25%, dyssocial 19%; female probands-nonalcoholics 8%, mild 18%, severe 33%, dyssocial 24%; p <.001). Cross-fostering analysis of the probands with adoptive/stepparents indicated little difference between nonalcoholic and mild alcoholic probands and suggests greater influence of biological parents for severe subtype probands compared to other probands. CONCLUSIONS: These results suggest construct validity for the alcoholism typology as distinguishing subtypes with differing degrees of familial liability to alcoholism. The typology may be useful when employing an extreme comparison strategy in genetic studies of alcohol dependence.

Family history influence on drug abuse severity and treatment outcome.

Influence of parental alcohol/substance abuse on methadone maintenance therapy (MMT) outcome was examined in 164 DSM-III-R opioid dependent adults with no other current DSM Axis I disorder. Family history positive patients had more DSM-III-R opioid dependence symptoms and were more likely to be classified as severely dependent. However, when placed on identical daily doses of methadone (50 mg), they had lower rates of illicit opioid use but higher rates of cocaine use than family history negative patients. Both effects remained significant after adjusting for gender and race. These results suggest that common genetic factors may underlie both susceptibility to heroin dependence and response to therapeutic methadone treatment.

A twin study on sensation seeking, risk taking behavior and marijuana use.

The contribution of genetic and environmental factors to the covariation between risk-taking and marijuana use was assessed in adolescent twins. Genetic factors were found to significantly influence some traits (i.e. risk-taking attitude), while familial environmental factors were important for others (i.e. sexual promiscuity). For marijuana use, genetic and environmental factors were equally important; however, the association between risk taking and marijuana use may not be comparable for different behaviors. Results suggest that different etiological factors may underlie various risk taking traits which is relevant to both prevention efforts and attempts to identify genes involved in risk taking and shared genetic influences with substance use.

Environmental transmission of DSM-IV substance use disdorders in adoptive and step families.

BACKGROUND: One factor contributing to the 3- to 5-fold increase in risk for substance use disorders (SUDs) among children of alcoholics may be the rearing environment. These influences may include availability of substances, modeling of SUDs, inadequate parenting, or other factors. The contribution of parental environmental influences on offspring with SUDs may be estimated independently of genetic influences through assessment of adoptees raised by nonbiological parents. METHODS: Relative risk of SUDs was assessed in adult adoptees (N = 442) of alcoholic and nonalcoholic adoptive parents as well as in stepchildren (N = 1859) with alcoholic or nonalcoholic stepfathers who participated in the community-based National Longitudinal Alcohol Epidemiologic Survey (NLAES). RESULTS: Rearing by an alcoholic adoptive mother was associated with increased DSM-IV alcohol abuse. Rearing by an alcoholic adoptive father was predictive of adoptees' illicit drug use, as well as DSM-IV drug dependence. Rearing by an alcoholic stepfather was predictive of stepchild DSM-IV alcohol abuse, illicit drug use, and drug dependence, whereas an alcoholic stepmother was associated with increased illicit drug use in the stepchild. Alcoholism in adoptive parents or step parents did not increase risk for offspring DSM-IV alcohol dependence. In both adoptive and biological families, there was a subadditive interaction of mother by father alcoholism such that the rate of substance abuse when both parents were alcoholic was less than that expected based on the additive effects of each alcoholic parent. CONCLUSIONS: Rearing by an alcoholic parent had a greater influence on alcohol abuse by offspring than on alcohol dependence. The increased risk of proband illicit drug use and drug dependence associated with paternal alcoholism suggested nonspecificity of environmental transmission. Both maternal and paternal cultural transmission effects influenced offspring SUDs.

Weekly patterns of drug treatment attendance.

OBJECTIVES: This study examined weekly patterns of drug treatment attendance in relation to date of welfare payment receipt and reason for treatment absence. METHODS: Treatment attendance by Medicaid-eligible pregnant women who were drug dependent was examined by calendar week over a 29-month period. RESULTS: Time series analyses showed that attendance was lower during week 1 than week 4. Drug use was the most frequently reported reason for treatment absence during week 1 (25%) but was not reported as a reason during week 3. CONCLUSIONS: Drug-dependent outpatients had increased absences associated with illicit drug use during the first week of the month when welfare payments were received. The generalizability of the findings is unknown.

The relationship between parental history and substance use severity in drug treatment patients.

The authors explored the relationship between the history of parental problematic alcohol and drug use and their adult children's alcohol and drug use disorders. Subjects were 347 admissions to an outpatient substance abuse program. There was a positive relationship between the number of parents affected by alcohol and/or drug problems and the percentage of probands with co-existing alcohol and drug use disorders for probands with alcohol use disorders but not for those with only drug abuse. Probands with two affected parents had significantly higher alcohol abuse scores and drug, family, and psychiatric composite test scores than those with a negative family history. This preliminary study indicates that the severity of a proband's substance use disorder may be influenced by parental substance use history.

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.

Extension of a typology of alcohol dependence based on relative genetic and environmental loading.

Mild, severe, and dyssocial subtypes of alcohol dependence, previously identified among Caucasian men from the Epidemiologic Catchment Area study, were also identified among Caucasian men and women with DSM-IV alcohol dependence from the National Longitudinal Alcohol Epidemiologic Survey (n = 2,703; 1,746 respectively). These subtypes were not identified among African American and Hispanic American men or women with DSM-IV alcohol dependence. Among Caucasians with alcohol dependence, the subtypes were characterized by differential loading on three dimensions: genetic, general environmental, and dyssocial environmental symptom scales developed in a prior twin study. The mild subtype (60% of men and 66% of women) was distinguished by low mean scores on all three scales; the dyssocial subtype (24% of men and 20% of women) by low mean genetic and general environmental scores but high mean dyssocial environmental scores; and the severe subtype (16% of men and 14% of women) by high scores on the genetic and general environmental scales. These subtypes also showed the expected distinctions in clinical characteristics. The severe subtype showed greater comorbid drug dependence and major depression, more treatment seeking, and a higher prevalence of parental alcoholism. The severe subtype also showed significantly greater genetic influence adjusted for overall severity of alcohol dependence (genetic ratio). Only the severe subtype showed a pattern of scale scores and clinical characteristics suggestive of substantial genetic influence. The present study indicates a robustness of the typology originally developed among DSM-III alcohol-dependent Caucasian men by empirical extension of the subtypes to a different sample of Caucasian men and, separately, Caucasian women. The use of this typology may aid in distinguishing between Caucasian alcohol-dependent individuals on the basis of relative genetic influence, enabling genetic, behavioral, and epidemiological investigations to reduce genetic or environmental "noise" and better focus on specific aspects of alcohol dependence.

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 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.

Twin closeness and co-twin risk for substance use disorders: assessing the impact of the equal environment assumption.

Various environmental variables are hypothesized to operate differentially within identical and fraternal twin pairs. To the extent that these factors are correlated with behavioral outcomes, such as alcohol or drug abuse, traditional twin studies of concordance may be biased. Self-ratings of within-pair emotional closeness, assessed in 169 same-sex twin pairs ascertained through alcohol and drug treatment centers, were used to determine the impact of the twin relationship on concordance for alcohol dependence (N = 130 twin pairs) and other drug abuse and/or dependence (N = 85 twin pairs). In general, identical twin pairs reported significantly closer relationships than fraternal twin pairs, and female twin pairs reported significantly closer relationships than male twin pairs. The data did not indicate an overall effect of closeness on co-twin risk for alcohol dependence. In contrast, closeness was significantly related to co-twin risk for other drug abuse and/or dependence. However, the MZ/DZ concordance difference for other drug abuse and/or dependence remained significant when the effects of within-pair closeness were controlled. Thus, the initial zygosity and sex differences in concordance for substance use disorders cannot be explained solely by differences in twin relationship due to closeness as assessed in this study.

Tobacco use for identifying pregnant women at risk of substance abuse.

OBJECTIVE: To examine the effectiveness of current smoking status as a rapid screening tool to identify pregnant women at risk of heavy alcohol and/or illicit drug use. STUDY DESIGN: Women (N = 92) seeking prenatal care were interviewed to assess lifetime and recent tobacco, alcohol and illicit drug use. Rates of recent heavy alcohol and illicit drug use were compared in current smokers and nonsmokers. RESULTS: All subjects reporting recent heavy alcohol and/or illicit drug use were current smokers; none were nonsmokers. CONCLUSION: Obstetric screening of pregnant women for current smoking status seems to be a cost-effective method of identifying those at risk of antepartum heavy alcohol and/or illicit drug use.

Cost-effectiveness of treatment for drug-abusing pregnant women.

Neonatal intensive care unit (NICU) and drug treatment costs were compared in two groups of pregnant drug abusing women: 100 admissions to a multidisciplinary treatment program and active in care at the time of delivery and 46 controls not entering drug treatment. Clinical measures included urine toxicology at delivery, infant birthweight. Apgar scores and need for and duration of NICU services. Cost measures included drug treatment and NICU costs. Treatment patients showed better clinical outcome at delivery, with less drug use and higher infant estimated gestational age, birthweight and Apgar scores. Infants of treatment patients were also less likely to require NICU services and, for those that did, had a shorter stay. When total cost was examined (including drug treatment), mean net savings for treatment subjects was $4644 per mother/infant pair. The study demonstrates the cost-effectiveness of treatment for pregnant drug abusing women, with savings in NICU costs exceeding costs of drug treatment.

Subtypes of alcohol-dependent men: a typology based on relative genetic and environmental loading.

Using scales that distinguish between relative genetic and environmental loading, cluster analysis was used to identify three subtypes of alcohol dependence in Caucasian men from the Epidemiologic Catchment Area study (n = 911). Although all subjects met DSM-III criteria for alcohol dependence, only the severe subtype showed evidence of substantial genetic influence. When compared on a range of clinical characteristics, the mild subtype (53% of the sample) was typically least adversely affected and the severe subtype (17%) most affected, with the dyssocial subtype (30%) falling between. Severe subtype subjects had significantly greater comorbid drug dependence and were at least four times more likely than mild subjects to have sought treatment for alcohol problems. Ratio of genetic scale score to total symptom count (genetic ratio) was highest for the severe subtype (mean = 0.37), and negatively correlated with age of first alcohol problem (rs = -0.16) and years between first intoxication and first problem (rs = 0.19). No significant correlations were found between these clinical features and genetic ratio for the mild or dyssocial subtypes. Use of these scales and subtypes may improve our ability to detect specific gene effects in genetic linkage studies and to identify environmental influences in behavioral and epidemiological studies.

Indicators of genetic and environmental influences in drug abusing individuals.

To assess relative contribution of genetic and environmental influences in individual cases of drug abuse/dependence, separate scales were constructed from DIS (version III) drug symptom items. Using data from 38 MZ and 35 DZ male twin pairs, items with significant MZ/DZ differences in probandwise concordance were assigned to a genetic scale whereas items without significant MZ/DZ differences were assigned to an environmental scale. As expected, significant differences were found between MZ and DZ twins in intraclass correlations for the genetic but not environmental scale. Genetic scores on drug and alcohol scales were correlated (r = 0.40), whereas environmental scales were not. When scores on the genetic scales were compared, the correlation between drug and alcohol scores within individuals was similar to that across MZ twins, both of which were higher than the correlation across DZ twins. These results suggest (1) relative contribution of genetic and environmental influences in individual cases of drug dependence can be assessed, and (2) common genetic mechanisms may be involved in alcohol and drug dependence.

Malignant fibrous histiocytoma of the spermatic cord.

PURPOSE: We analyzed 26 cases of malignant fibrous histiocytoma and report our conclusions regarding the diagnosis, pathology and treatment of this unusual tumor. MATERIALS AND METHODS: We reviewed 25 previously reported cases of malignant fibrous histiocytoma of the spermatic cord and report 1 additional case. Further data on patient survival and tumor recurrence rates were obtained from some of the previous authors. RESULTS: Of 26 patients 5 are long-term survivors (more than 5 years). Longest reported followup is 14 years. However, malignant fibrous histiocytoma has recurred as late as 6 years after surgery. To date 4 deaths have been reported, including 1 unrelated to the tumor and 3 from metastatic tumor. Disease recurred in 5 patients. In no case was there local lymph node involvement at surgery. CONCLUSIONS: Malignant fibrous histiocytoma presents earlier in the spermatic cord than at other sites and seems to have a more favorable prognosis. Ultrasound may aid in the diagnosis. Definitive treatment is radical orchiectomy but localized radiotherapy may decrease local recurrence rates. Satellite lesions at surgery indicate a poorer prognosis. Metastases may develop late in the lungs or mesentery, and so long-term followup is necessary.

Indicators of genetic and environmental influence in alcohol-dependent individuals.

Although much is known about genetic and environmental influences in alcohol dependence at the population level, little is known about the relative contribution of such influences on individuals. As an initial step toward individual assessment, concordance for the Diagnostic Interview Schedule, version III alcohol symptoms was determined in a sample (n = 113) of male monozygotic (MZ) and dizygotic (DZ) twins. Items were assigned to a genetic or environmental scale on the basis of significant MZ/DZ differences in proband-wise concordance rates. Weights were assigned to items based on factor analyses. For the genetic scale, significant differences were found between MZ and DZ intraclass correlations. No significant differences were found between MZ and DZ correlations on the environmental scale. When scores on the environmental scale were controlled, genetic scale scores were correlated with earlier age of onset of alcohol problems and a shorter interval between first intoxication and onset of alcohol problems. When scores on the genetic scale were controlled, environmental scale scores were correlated with later age of onset of alcohol problems and a longer interval between first intoxication and onset of alcohol problems. These results suggest it is possible to assess relative influence of genetic and environmental factors in individual cases of alcohol dependence.

HIV infection and AIDS risk behaviors among injecting drug users entering methadone treatment: an update.

Trends in HIV infection and AIDS risk behaviors among injecting drug users (IDUs) were assessed through a series of nonblinded point-prevalence surveys conducted between 1987 and 1991 with admissions to methadone treatment in eight areas, including New York City; Asbury Park and Trenton, New Jersey; Philadelphia; Baltimore; Chicago; San Antonio, Texas; and Los Angeles County. Over the 5-year period, significant changes in HIV seropositivity were found in two of the eight cities, with seroprevalence decreasing in Asbury Park from 43.1 to 21.2% and increasing from 10.1 to 17.6% in Chicago. Initially high levels of injection-related risk behaviors decreased substantially across cohorts in most cities, except for San Antonio and Los Angeles, where risk levels remained high. Sexual risk behaviors continued at high levels in all cities, suggesting relatively little sexual risk reduction during the course of the study.

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.