Objective: The DSM-IV work group asked researchers and clinicians to subtype substance dependent individuals according to the presence or absence of physiological symptoms. A recent report from the Collaborative Study on the Genetics of Alcoholism demonstrated that among alcohol-dependent men and women, a history of tolerance or withdrawal was associated with a more severe clinical course, especially for individuals with histories of alcohol withdrawal. This article evaluates similar distinctions among subjects in the collaborative study who were dependent on marijuana, cocaine, amphetamines, or opiates. Method: Structured interviews gathered information from 1,457 individuals with a lifetime diagnosis of marijuana dependence, 1,262 with histories of cocaine dependence, 647 with amphetamine dependence, and 368 subjects with opiate dependence. For each drug, the clinical course was compared for subjects whose dependence included a history of withdrawal (group 1), those dependent on each drug who denied withdrawal but reported tolerance (group 2), and those who denied both tolerance and withdrawal (group 3). Results: The proportion of dependent individuals who denied tolerance or withdrawal (group 3) ranged from 30% for marijuana to 4% for opiates. For each substance, individuals in groups 1 and 2 evidenced more severe substance-related problems and at least a trend for greater intensities of exposure to the drug; those reporting withdrawal (group 1) showed the greatest intensity of problems. Conclusions: The designation of dependence in the context of tolerance or withdrawal identifies individuals with more severe clinical histories. These results support the importance of the designation of a physiological component to dependence, especially for people who have experienced a withdrawal syndrome.(Am J Psychiatry 1999; 156:41-49)

A 5-year prospective evaluation of attributes associated with suicide attempts among alcohol-dependent persons identified factors that contributed to a small but significant proportion of the variance for future suicidal behavior.

Objective: A low level of response (LR) to alcohol as measured through alcohol challenges is an early-appearing, genetically influenced characteristic that predicts the risk of heavier drinking and alcohol problems. A less expensive and more easily used measure of LR, the retrospective Self-Rating of the Effects of Alcohol (SRE) questionnaire, also relates to alcohol intake and problems but has not been evaluated for its ability to predict alcohol-related problems 5 years later. Method: At Time 1, 95 18-to 35-year-old (mean age: 25.9 years) subjects who were offspring from families participating at the San Diego site of the Collaborative Study on the Genetics of Alcoholism (COGA) were administered the SRE and evaluated regarding alcohol, drug, and demographic characteristics using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview. Follow-up interviews (Time 2) using the SSAGA were completed an average (SD) of 5.4 (1.34) years later for approximately 80% of the original sample. Re-

-This paper examines the clinical characteristics associated with tobacco use and nicotine dependence in a large sample of alcohol-dependent subjects. The goal was to determine if the characteristics of the alcohol use history were associated with the smoking status, even after controlling for additional characteristics, such as the antisocial personality disorder, other drug dependence and gender. As part of the Collaborative Study on the Genetics of Alcoholism, a semi-structured interview, including a detailed history of alcohol and tobacco use, was administered to 1005 alcohol-dependent men and women, made up of 658 (65.5%) current smokers, 167 (16.6%) former smokers, and 180 (17.9%) non-smokers. Among former smokers, 50.3%, and among current smokers, 72.8% had ever been nicotine-dependent (DSM-III-R). Current smokers and nicotine-dependent subjects had a greater severity of alcohol dependence, even as evaluated through logistic regression analyses in which gender and associated diagnoses were considered. The data also enabled us to study the relationships among depression, nicotine dependence, and alcohol dependence, with most of the correlation occurring for substance-induced, not independent, mood disorders.

ABSTRACT. Objective: The low level of response (LR) to alcohol is an endophenotype related to heavier drinking and alcohol problems. Structural equation models (SEMs) indicate LR affects alcohol outcomes (ALCOUT) both directly and through mediation by drinking in peers (PEER), alcohol expectancies (EXPECT), and drinking to cope with stress (COPE), with some variation depending on the sample tested. This article presents the fi rst full test of this LR-based model in young subjects from the Collaborative Study on the Genetics of Alcoholism (COGA). Method: Data were generated from 325 12-to 22-year-old (47.4% male) drinking offspring from COGA families, using the SelfReport of the Effects of Alcohol questionnaire to determine LR early in the drinking career and a validated, structured interview for demography and alcohol use/problem patterns. Standardized questionnaires were used to measure PEER, EXPECT, and COPE, with the model tested through the maximum likelihood estimation for analyses of the variance/covariance matrix using both Amos and Mplus. Results: The SEM yielded good fi t characteristics and explained 59% of the variance, with LR relating both directly to ALCOUT and as partially mediated by PEER and COPE. Although GENDER related to both LR and ALCOUT in the model, and AGE related to ALCOUT, the SEM results were invariant across both AGE and GENDER, with generally similar invariant results regarding the presence or absence of an alcohol-use disorder diagnosis. Conclusions:The results support the applicability of the LR-based model of heavy drinking and alcohol problems in the COGA offspring, a group with different demography compared with the two other samples of adolescents tested to date. The modest differences observed across samples will be evaluated in future research to enhance understanding of how the model operates across socioeconomic groups. (J. Stud. Alcohol Drugs 70: [436][437][438][439][440][441][442][443][444][445] 2009)

The data suggest that over 5 years the DSM-IV diagnosis of alcohol dependence predicts a chronic disorder with a relatively severe course, while DSM-IV alcohol abuse predicts a less persistent, milder disorder that does not usually progress to dependence.

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