The five-year predictive validity of each of the seven DSM-IV items for alcohol dependence among alcoholics

BACKGROUND: Information about the prognostic implications of a DSM-IV diagnosis of alcohol dependence is important to both clinicians and researchers. In this regard, only limited data are available on the performance of specific diagnostic items. METHODS: This study reports data gathered with a structured, validated interview with 642 alcohol-dependent men and women from the Collaborative Study of the Genetics of Alcoholism (COGA). The goals were to evaluate the ability of each of the DSM-IV dependence items to predict the occurrence over the next 5 years of a broad pattern of 27 alcohol-related problems. For comparison, similar data are reported regarding the performance of abuse criteria for 516 additional subjects. RESULTS: The results revealed that dependence item 3 (use of alcohol in larger amounts) was the only criterion that did not relate significantly to outcome, and indicated that the dependence criteria related relatively similarly to different types of outcomes among alcoholics. No specific combination of diagnostic items stood out in predicting outcome but, rather, the span of items generally performed well. CONCLUSIONS: These data support the potential usefulness of the DSM-IV dependence criteria.     

Rates and correlates of relapse among individuals in remission from DSM-IV alcohol dependence: a 3-year follow-up

Background: There is little information on the stability of abstinent and nonabstinent remission from alcohol dependence in the general U.S. population. The aim of this study was to examine longitudinal changes in recovery status among individuals in remission from DSM‐IV alcohol dependence, including rates and correlates of relapse, over a 3‐year period. Methods: This analysis is based on data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of U.S. adults aged 18 years and older originally interviewed in 2001 to 2002 and reinterviewed in 2004 to 2005. The Wave 1 NESARC identified 2,109 individuals who met the DSM‐IV criteria for full remission from alcohol dependence. Of these, 1,772 were reinterviewed at Wave 2, comprising the analytic sample for this study. Recovery status at Wave 2 was examined as a function of type of remission at Wave 1, with a focus on rates of relapse, alternately defined as recurrence of any alcohol use disorder (AUD) symptoms and recurrence of DSM‐IV alcohol dependence. Logistic regression models were used to estimate the odds of relapse among asymptomatic risk drinkers and low‐risk drinkers relative to abstainers, adjusted for a wide range of potential confounders. Results: By Wave 2, 51.0% of the Wave 1 asymptomatic risk drinkers had experienced the recurrence of AUD symptoms, compared with 27.2% of low‐risk drinkers and 7.3% of abstainers. Across all ages combined, the adjusted odds of recurrence of AUD symptoms relative to abstainers were 14.6 times as great for asymptomatic risk drinkers and 5.8 times as great for low‐risk drinkers. The proportions of individuals who had experienced the recurrence of dependence were 10.2, 4.0, and 2.9%, respectively, and the adjusted odds ratios relative to abstainers were 7.0 for asymptomatic risk drinkers and 3.0 for low‐risk drinkers. Age significantly modified the association between type of remission and relapse. Differences by type of remission were not significant for younger alcoholics, who had the highest rates of relapse. Conclusions: Abstinence represents the most stable form of remission for most recovering alcoholics. Study findings highlight the need for better approaches to maintaining recovery among young adults in remission from alcohol dependence, who are at particularly high risk of relapse.     

Acculturation, drinking, and alcohol abuse and dependence among Hispanics in the Texas-Mexico border

Background:  Acculturation has been linked to an increased prevalence of alcohol‐related problems. However, most of the research has been conducted with Hispanic populations in metropolitan areas of the United States, none of which is on the U.S.–Mexico border. This study examines the association between acculturation, heavy episodic drinking, and DSM‐IV alcohol abuse and dependence among Hispanics in the Texas–Mexico border. Methods:  The study used data from a survey conducted (2002 to 2003) along the Texas–Mexico border and included 472 male and 484 female Hispanic adults from El Paso, the Rio Grande Valley, and colonias. Based on the Acculturation Rating Scale for Mexican Americans‐II scale, respondents were coded into 4 acculturation categories: “very Mexican oriented,”“Mexican bicultural,”“Anglo bicultural,” or “very Anglo/Anglicized.”. Results:  Acculturation was related to lower rates of alcohol use disorders among men and a higher frequency of heavy episodic drinking among women. Multivariate analyses indicate that men who report heavy episodic drinking and those who are “very Mexican,”“bicultural Mexican,” or “bicultural Anglo” are more at higher risk for alcohol abuse and/or dependence compared with “very Anglo/Anglicized” men. For women, acculturation level did not predict alcohol disorders. Statistical analyses included testing for bivariate associations and multivariate logistic regression predicting heavy episodic drinking alcohol abuse or dependence. Conclusions:  This study suggests that acculturation has different effects on drinking for men and women. This finding needs some attention as literature also indicates that women drink more and may develop more alcohol‐related problems as they acculturate. This increase in women’s drinking is probably because of U.S. society’s more liberal norms governing female drinking. The “bimodal” distribution of risk, in which only men in “very Anglo” group are at a lower risk than the others, may be unique to the Border. The association between acculturation and alcohol use disorders does not appear to be linear and the effect of acculturation is not uniform on individuals’ drinking behavior.     

A Rasch model analysis of DSM-IV Alcohol abuse and dependence items in the National Epidemiological Survey on Alcohol and Related Conditions

BACKGROUND: Questions persist about the diagnoses of alcohol abuse and alcohol dependence as defined by Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV). These questions center around the performance of individual alcohol use disorder (AUD) criteria and the nature of items used to assess them. In this study, we conduct in-depth analyses of interview items used to assess alcohol abuse and dependence. METHOD: We conducted Rasch model analyses of responses to 33 items assessing alcohol abuse and dependence criteria in the National Epidemiological Survey on Alcohol and Related Conditions, a nationally representative sample of 34,550 participants. We also examined whether items performed differentially by gender, race/ethnicity, age, education, and time frame of assessment (i.e., past year vs lifetime). RESULTS: A single latent dimension explained the vast majority of shared variance among the items. Abuse symptoms were not of consistently lower severity than dependence symptoms, and some were consistently prone to differential functioning across subgroups. Items related to tolerance also functioned differentially across subgroups especially in the comparison of past-year symptoms between young adults (ages 18-24) and older adults. Items differed widely in their empirically estimated severity, even when they were intended to assess the same DSM-IV criterion. CONCLUSIONS: The use of Rasch model analyses demonstrated the essential unidimensionality of AUD criteria and the lack of hierarchical ordering between abuse and dependence criteria, as well as potential sources of bias in the abuse diagnosis and the tolerance criterion. Results highlight that the prevalence and even the meaning of AUD criteria can differ substantially depending on the wording of items used to assess them. Implications for assessment of specific DSM criteria and for development of DSM-V are discussed.     

Multicenter validation study of the %CDT TIA kit in alcohol abuse and alcohol dependence

Background: Carbohydrate-deficient transferrin (CDT) and γ-glutamyl transferase (GGT) are used as biomarkers of alcohol misuse. The aim of this study was to evaluate, in terms of sensitivity and specificity, the performance of the new Bio-Rad %CDT TIA kit and GGT assay for identifying alcohol abuse and alcohol dependence (according to the DSM-IV criteria).
Methods: An open multicenter study (30 centers) over 3 months, including patient groups of "abusers,""dependents," and controls, was conducted in France.
Results: In alcohol abuse, the sensitivity of GGT was 0.56, and that of CDT was 0.80; in alcohol dependence, the sensitivity of GGT was 0.86, and that of CDT was 0.91. The specificity of GGT was 0.77, and that of CDT was 0.83. The association of GGT with CDT increased sensitivity for alcohol abuse to 0.90 and for alcohol dependence to 0.99, but it appreciably decreased specificity (0.63).
Conclusions: %CDT is the better screening marker for alcohol abuse and dependence, but GGT is still a useful marker for the detection of alcohol dependence. As an assay method, the second-generation Bio-Rad %CDT immunoassay can be recommended for routine CDT measurement.     

Alcohol dependence and abuse diagnoses: concurrent validity in a nationally representative sample

The Alcohol Dependence Syndrome concept has had a widespread influence on the major nosological classification systems, most recently with its operationalization as DSM-IV alcohol dependence. Although many studies have provided evidence of the validity of the Alcohol Dependence Syndrome in clinical samples, little validation work has been conducted in general population samples on DSM-IV alcohol dependence or the distinction of DSM-IV alcohol dependence from DSM-IV alcohol abuse. We therefore examined the cross-sectional validity of DSM-IV alcohol dependence and abuse in 27,616 household residents who participated in a 1992 national survey on alcohol use disorders. Validity was investigated by testing the association of a set of five "criterion" variables, external to the alcohol diagnostic criteria, with dependence and abuse diagnoses. Results indicated that dependence diagnoses were significantly associated with all criterion variables when compared with those with no diagnosis and also when compared with alcohol abuse. This supported the separation of dependence from abuse. Abuse diagnoses were associated with some, but not all, criterion variables when compared with subjects with no diagnosis. This report replicates many aspects of a similar investigation in a community sample of household residents. Implications for the next steps in research are discussed.     

Cannabinoid receptor 1 gene is associated with alcohol dependence

Background: Alcohol dependence (AD) vulnerability is determined by a complex array of genetic factors. Given the potential role of endocannabinoid system in AD, polymorphisms within cannabinoid receptor 1 gene (CNR1) have been potentially associated with susceptibility to this disease. We thus aimed to examine the relationship between 3 allelic variants of CNR1 (rs6454674, rs1049353, and rs806368) and AD. Methods: Genotyping of the aforementioned polymorphisms was carried out by PCR in 298 male alcoholics (187 of them with AD) and 155 healthy controls. Single‐marker, haplotype, and interaction analysis were performed to analyze the influence of CNR1 gene on AD susceptibility. Results: We found an association between CNR1 gene and AD after haplotype analysis. Alcoholic patients with TGT haplotype (corresponding to rs6454674‐rs1049353‐rs806368 polymorphisms in this order) were less prone to have AD (p = 0.017). Besides, alcoholics with a G/T substitution of the first marker (GGT haplotype) or a C/T substitution of the third marker (TGC haplotype) were more likely to develop AD (p = 0.006 and 0.004, respectively) and an interaction was found between the G allele of rs6454674 single nucleotide polymorphism (SNP) and the C allele of rs806368 SNP (p = 0.009). Conclusions: Our findings support previously reported associations of CNR1 with dependence to alcohol and other substances and emphasizes the relevance of endocannabinoid system in AD.     

Ten-year trends (1992 to 2002) in sociodemographic predictors and indicators of alcohol abuse and dependence among whites, blacks, and Hispanics in the United States

Background: The objective of this paper is to examine 10‐year trends (1992 to 2002) in the number and type of indicators of DSM‐IV abuse and dependence among whites, blacks, and Hispanics in the United States. Methods: Data are from the 1991 to 1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES; n = 42,862) and the 2001 to 2002 National Epidemiologic Study on Alcohol and Related Conditions (NESARC; n = 43,093). Both surveys used multistage cluster sample procedures to select respondents 18 years of age and older from the U.S. household population. Results: Increases in the prevalence of alcohol abuse between 1992 and 2002 seem associated with a rise in the prevalence of the indicator for “hazardous use.” which usually means reports of driving after drinking. The decrease in dependence was not associated with changes in a particular indicator. In addition, both in 1992 and 2002, 12.3 to 15.4% of the men and 5.2 to 7.9% of the women were diagnostic “orphans.” These respondents reported 1 or 2 indicators of alcohol dependence as present. Conclusions: The observed trends in number and types of indicators of DSM‐IV alcohol abuse and dependence were probably triggered by a complex interplay between individuals’ volume and pattern of drinking and reactions from the drinkers’ social environment. The close association between hazardous use of alcohol and the prevalence of abuse deserves further discussion. A medical diagnostic category should not be so dependent on a criterion that may be influenced by social situations. It is necessary to understand more about diagnostic “orphans” to better design interventions to address their problems.     

DSM-IV criteria endorsement patterns in alcohol dependence: relationship to severity

Background: In DSM‐IV, the diagnostic threshold for alcohol dependence (AD) is met when a patient presents with at least 3 of 7 criteria. We have computed the predictive value for each individual DSM‐IV AD criterion, and examined subtypes of AD criteria endorsement patterns and their associated severity indicators for community‐dwelling AD individuals. Methods: We utilized data from the 2001 to 2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Positive predictive values (PPV) for DSM‐IV AD were computed for each of the individual criteria. Patterns of criteria endorsements were identified by latent class analysis (LCA). Sociodemographic status, age of onset and duration of AD, patterns of drinking, and drinking treatment history, were conditional on DSM criteria endorsement clusters, as indicators of the respondents’ clinical severity. Results: At the individual criterion level, the single criterion with the greatest PPV was D7—“Activities given up” with ～95% of drinking individuals who endorsed this DSM criterion correctly diagnosed as having DSM‐IV AD. In addition to D7, only D5—“Physical/Psychological problems”, and D6—“Time spent” had a PPV for AD substantially >50%. The LCA of AD endorsement patterns yielded a 6‐cluster solution. The most common response pattern (34.5% of those with AD) was endorsement of 5 criteria: D1—“Quit/Control,” D2—“Larger/Longer,” D3—“Tolerance,” D4—“Withdrawal,” and D5—“Physical/Psychological problems.” The most severe cluster (14%) was comprised of those who were likely to endorse 7/7 criteria. Cluster 1 (8.3%) did not include an endorsement of withdrawal, despite a heavy pattern of alcohol consumption. Unmarried status was associated with more severe criteria endorsement patterns. Conclusions: The present findings indicate a Guttman‐like scaling of endorsement which yielded associations with severity for some of the concurrent indicators included in the analysis. However, severity measures did not always increase with DSM‐IV AD criterion endorsement counts. Although endorsement of 6/7 or 7/7 criteria was associated with greater severity across a variety of indicators, fewer criteria were randomly associated with these measures. These data do not support the use of AD symptom counts as a phenotypic dependent variable. At least 2 extant diagnostic criteria showed relatively low PPV for AD, indicating a need for further assessment of these criteria with new symptoms or re‐wording of the current symptom items.     

Screening for alcohol problems in the U.S. general population: comparison of the CAGE,RAPS4, and RAPS4-QF by gender,ethnicity, and service utilization. Rapid Alcohol Problems Screen

BACKGROUND: The purpose of this study was to compare the performance (sensitivity and specificity) of two brief screening instruments, CAGE and the Rapid Alcohol Problems Screen 4 (RAPS4), against ICD-10 and DSM-IV criteria for alcohol dependence and abuse in a representative sample of the U.S. adult household population by gender, ethnicity, and service utilization (emergency room and primary care) in the last year. METHODS: Data are from the Alcohol Research Group's 2000 National Alcohol Survey (n = 7612), which is a computer-assisted telephone interview survey of the U.S. general population 18 and over in all 50 U.S. states and the District of Columbia. RESULTS: Sensitivity of the RAPS4 (0.86) was better than the CAGE (0.67) given similar specificity (0.95 vs. 0.98) and outperformed the CAGE for alcohol dependence across all gender, ethnic, and service utilization groups, except among blacks and Hispanics. The RAPS4 also performed equally well for females and males (0.88 vs. 0.85), whereas sensitivity of the CAGE was lower for females. Although sensitivity of the RAPS4 was better than the CAGE for alcohol abuse, sensitivity was low for both (0.56 and 0.36, respectively). When quantity-frequency (QF) questions (drinking five or more drinks on at least one occasion during the last year and drinking as often as once a month during the last year) were added to the RAPS4, the RAPS4-QF performed significantly better for alcohol abuse and outperformed the CAGE at a cut point of one across all gender, ethnic, and service utilization groups. The RAPS4-QF appeared to be most sensitive for alcohol abuse among both males and females reporting emergency room use (0.90). CONCLUSIONS: The data suggest that the RAPS4 outperforms the CAGE in this general population sample. The addition of a QF question to the RAPS4 improves performance in relation to sensitivity for alcohol abuse, and the RAPS4 and RAPS4-QF may be the instruments of choice in brief screening for alcohol use disorders. Additional research is needed to further explore these issues.     

DSM-III-R and Proposed DSM-IV Alcohol Abuse and Dependence, United States 1988: A Nosological Comparison

The purpose of the present study was to compare DSM-III-R and the proposed DSM-IV (options 1 and 2) diagnostic criteria for alcohol abuse and dependence in a representative sample of the United States general population. Alcohol abuse and dependence diagnostic categories were contrasted in terms of prevalence and overlap. The prevalences of DSM-III-R and DSM-IV diagnoses of alcohol abuse and dependence combined were remarkably similar. However, disaggregation of abuse and dependence diagnoses showed that there were major discrepancies between the classification systems. Reasons for these discrepancies are discussed in terms of differences in the number of diagnostic criteria and the content of the DSM-III-R and DSM-IV abuse and dependence categories, the requirement for physiological dependence in DSM-IV classifications, the relationship between the abuse and dependence categories, and the impact of the duration criteria.     

Parallels to early onset alcohol use in the relationship of early onset smoking with drug use and DSM-IV drug and depressive disorders: findings from the National Longitudinal Epidemiologic Survey

This paper endeavored to determine (1) if early onset of regular tobacco use is as predictive of drug use and depressive disorders as it is of alcohol use disorders; and (2) if a biological commonality, as measured by a family history of alcoholism and both early onset and severity of disease, among all three disorders can be evidenced in a large nationally representative sample. Prevalences of lifetime drug use, drug abuse and dependence, and major depressive disorders, as well as indices of their severity, were compared among smoking groups defined by age at onset of regular tobacco use and among nonsmokers. Linear logistic regression analyses, controlling for important covariates, including a family history positive for alcoholism, were conducted to assess the relationship between age at smoking onset and drug use, abuse and dependence, as well as depressive disorders. Both objectives were met. Moreover, results suggest that smoking may play an equally, if not even more, insidious role than drinking in the use and development of dependence on illicit substances and depression.     

Excess mortality among HIV-infected patients diagnosed with substance use dependence or abuse receiving care in a fully integrated medical care program

Background: We examined the association between substance use (SU) disorder and mortality among HIV‐infected patients in a large, private medical care program. Methods: In a retrospective cohort design, HIV‐infected patients (≥14 years old) from a large health plan (Northern California) were studied to examine mortality associated with diagnosis of SU dependence or abuse over an 11‐year period. Results: At study entry or during follow‐up, 2,279 (25%) of 9,178 HIV‐infected patients had received a diagnosis of SU disorder. Diagnoses were categorized as alcohol dependence/abuse only, illicit drugs only, or both. Cause of death differed by the category of SU diagnosis. Mortality rates ranged from 35.5 deaths per 1,000 person‐years in patients with an SU disorder to 17.5 deaths among patients without an SU disorder. Regression results indicated mortality risk was significantly higher in all categories of SU disorder compared to no SU diagnosis (hazard ratios ranging from 1.65 to 1.67) after adjustment for SU treatment and confounders. Conclusions: A diagnosis of SU dependence/abuse is associated with higher mortality among HIV‐infected patients for whom access to medical services is not a significant factor.     

DSM-III-R and the Proposed DSM-IV Alcohol Use Disorders, United States 1988: A Nosological Comparison

The purpose of the present study was to compare DSM-III-R and the proposed DSM-IV diagnostic criteria for alcohol abuse and dependence in a representative sample of the United States general population. Alcohol abuse and dependence diagnostic categories were contrasted in terms of prevalence and overlap. The prevalence of DSM-III-R diagnoses of alcohol abuse and dependence combined (8.63%) was greater than the corresponding DSM-IV diagnoses (6.00%). Disaggregation of abuse and dependence diagnoses showed that the major discrepancy between the classification systems resided between the abuse categories. Reasons for the discrepancies are discussed in terms of differences in the content of the DSM-III-R and DSM-IV abuse categories, in the relationship that each abuse category shares with its respective dependence category, and the impact of the DSM-III-R duration criterion.     

Course of DSM-IV alcohol dependence in a community sample: effects of parental history and binge drinking

BACKGROUND: The role of positive family history in the etiology of alcohol dependence has been demonstrated repeatedly but little is known about the effect of this risk factor on the chronicity of alcohol dependence once it has begun. METHODS: We studied the effects of parental and sibling history in conjunction with frequency of binge drinking in a sample of 169 community residents who met criteria for DSM-IV alcohol dependence at the baseline interview. Subjects were re-interviewed approximately 1 year later and the status of their alcohol-dependence disorders (remitted or chronic) was determined. RESULTS: Parental history of alcoholism was significantly related to chronicity of alcohol dependence, as was frequency of binge drinking. CONCLUSIONS: Failure to find an effect for family history on chronicity would have suggested that the effect was transient, perhaps interacting with time-limited environmental vulnerability. The finding of a positive relationship between family history and chronicity suggests that the relationship between familial/ genetic background and alcohol dependence is stable.     

Adolescent substance abuse: the effects of alcohol and marijuana on neuropsychological performance

Background: Adolescence is a period in which cognition and brain undergo dramatic parallel development. Whereas chronic use of alcohol and marijuana is known to cause cognitive impairments in adults, far less is known about the effect of these substances of abuse on adolescent cognition, including possible interactions with developmental processes. Methods: Neuropsychological performance, alcohol use, and marijuana use were assessed in 48 adolescents (ages 12 to 18), recruited in 3 groups: a healthy control group (HC, n = 15), a group diagnosed with substance abuse or dependence (SUD, n = 19), and a group with a family history positive for alcohol use disorder (AUD) but no personal substance use disorder (FHP, n = 14). Age, drinks per drinking day (DPDD), percentage days drinking, and percentage days using marijuana were considered as covariates in a MANCOVA in which 6 neuropsychological composites (Verbal Reasoning, Visuospatial Ability, Executive Function, Memory, Attention, and Processing Speed) served as dependent variables. Results: More DPDD predicted poorer performance on Attention and Executive Function composites, and more frequent use of marijuana was associated with poorer Memory performance. In separate analyses, adolescents in the SUD group had lower scores on Attention, Memory, and Processing Speed composites, and FHP adolescents had poorer Visuospatial Ability. Conclusions: In combination, these analyses suggest that heavy alcohol use in adolescence leads to reduction in attention and executive functioning and that marijuana use exerts an independent deleterious effect on memory. At the same time, premorbid deficits associated with family history of AUD appeared to be specific to visuospatial ability.     

1994 Draft DSM-IV Criteria for Alcohol Use Disorders: Comparison to DSM-III-R and Implications

In 1994, DSM-IV will be published, with new criteria for alcohol abuse and dependence. Implications of the changes in criteria for alcohol use disorders were investigated by comparing the diagnoses made by the DSM-IV criteria and DSM-III-R criteria. The study was conducted in a sample of 424 patients in an inpatient alcohol rehabilitation unit in the New York metropolitan area. DSM-III-R and DSM-IV criteria showed similar results and high agreement for any alcohol use disorder (abuse and dependence combined). Alcohol dependence was also consistently diagnosed with DSM-III-R and DSM-IV criteria. Agreement between DSM-III-R and DSM-IV abuse diagnoses was very low. Compared with DSM-III-R, DSM-IV classified over three times as many patients as alcohol abusers, although those with alcohol dependence still overwhelmingly dominated the sample. With some fluctuations, the results were stable over Black, Hispanic, and White subgroups of patients. The direction of the findings was consistent with results from a national general population survey in that the prevalence of alcohol abuse increased in both studies. However, the clinical results alone would not have suggested the marked changes in relative prevalence of abuse and dependence that occurred in the general population when DSM-IV criteria were used in place of DSM-III-R. Research on diagnostic criteria limited to patient samples omits important information on the implications of changing aspects of the diagnostic criteria. The need for a coherent theory of alcohol abuse is highlighted.     

Platelet adenylyl cyclase activity as a state or trait marker in alcohol dependence: results of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence

BACKGROUND: There has been considerable interest in identifying biochemical markers indicative of a genetic predisposition to alcohol dependence ("trait markers"), as well as biochemical markers of recent alcohol drinking ("state markers"). Platelet adenylyl cyclase activity has been suggested as a trait and/or as a state marker related to alcohol dependence. We have now measured platelet adenylyl cyclase activity in more than 1400 well-characterized subjects, which allows us to investigate the influence of a broad range of factors on this activity. METHODS: Subjects were recruited as part of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence and were interviewed by using the WHO/ISBRA Interview Schedule. Adenylyl cyclase activity (basal, cesium fluoride [CsF]-, forskolin- and Gpp(NH)p-stimulated activities) was measured in platelet samples that were obtained at the time of interview. Data were analyzed by multivariate regression analyses. RESULTS: The multivariate analyses revealed that recent abstinence from alcohol was associated with diminutions in platelet adenylyl cyclase activities. A positive family history of alcohol dependence was associated with higher levels of adenylyl cyclase activities, and there was a significant interaction between the effect of alcohol consumption in the past month and family history of alcohol dependence; that is, the influence of alcohol consumption depended on whether the individual had a positive family history. A history of marijuana abuse also was associated with higher levels of platelet adenylyl cyclase activities, and a history of major depression was associated with lower levels of forskolin- and CsF-stimulated activities. Sex, race, and site of recruitment also affected some adenylyl cyclase activities, but there was no significant association of alcohol dependence or abuse with any of the platelet adenylyl cyclase activities. DISCUSSION: The large population and extensive characterization of subjects in this study provided an advantage over previous studies in which only the association of a few individual factors with adenylyl cyclase activity was investigated. The results demonstrate that although platelet adenylyl cyclase activity could be useful as a trait marker of alcohol dependence, its reliability in this regard is diminished by the influence of recent alcohol drinking and other variables. The associations between platelet adenylyl cyclase activities and marijuana abuse, as well as a history of depression, suggest that it may be worthwhile to study the genetic association of adenylyl cyclases (e.g., polymorphisms in the genes that code for particular adenylyl cyclase isoforms) with a predisposition to depression as well as to alcohol or marijuana abuse/dependence.     

Cigarette smoking and the risk for alcohol use disorders among adolescent drinkers

BACKGROUND: Cigarette smoking and alcohol use disorders (AUDs) are closely linked, but it is not clear whether higher rates of AUD among smokers are solely attributable to heavier drinking or, alternatively, whether smokers are more vulnerable to alcohol abuse and dependence than nonsmokers who drink comparable quantities. We sought to address this issue using data from a nationally representative U.S. sample of adolescents and young adults. Specifically, we analyzed the relationship between cigarette smoking, drinking, and AUDs. METHODS: Data were from the aggregated 2002 through 2004 U.S. National Survey on Drug Use and Health. Participants were randomly selected, household-dwelling adolescents and young adults (ages 12-20) from the noninstitutionalized, civilian population of the United States (N=74,836). Measurements included current DSM-IV alcohol abuse or dependence, number of drinks in the past 30 days, and past-year cigarette smoking, defined as having smoked more than 100 cigarettes across the lifetime and having smoked during the past year. RESULTS: Past-year smokers (prevalence=16.0%) drank in higher quantities than never-smokers, but were also at elevated risk for AUD when compared with never-smokers who drank equivalent quantities. The effect was observed across age groups, but was more prominent among younger adolescents. After adjusting for drinking quantity and sociodemographic variables, smokers had 4.5-fold higher odds of AUD than never-smokers [95% confidence interval (95% CI), 3.1-6.6]. Youths who reported smoking but did not cross the 100-cigarette threshold were at intermediate risk [odds ratio (OR), 2.3; 95% CI, 1.7-3.3]. Differences in AUD between smokers and never-smokers were most pronounced at lower levels of drinking. CONCLUSIONS: The results are consistent with a higher vulnerability to AUDs among smokers, compared with nonsmokers who drink equivalent quantities.