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Biomedical subjects

M A Schuckit

Publications and source records attributed to M A Schuckit.

At least 19 recordsLinked to original sources
PubMed2001

The clinical course of alcohol dependence associated with a low level of response to alcohol.

AIMS: To evaluate the clinical course of specific alcohol-related life problems and the risk for dependence on illicit drugs in individuals with relatively low and high levels of response (LR) to alcohol earlier in life. SUBJECTS: From among 439 men who were part of the 15-year follow-up of sons of alcoholics and controls, 108 were identified as having fulfilled criteria for DSM-III-R alcohol dependence. MEASURES: The LR to alcohol was originally evaluated following the consumption of 0.61 g/kg of ethanol at age 20 by determining the levels of change in subjective feelings of intoxication, body sway and several hormones such as cortisol. From the 453 original subjects, 450 completed a face-to-face 10-year follow-up evaluation, and 439 completed the 15-year protocol. FINDINGS: A comparison of the clinical course of 50 alcohol-dependent men with clearly low LR values at age 20 with that for 42 individuals whose LR scores were above the median revealed few differences. Those with a low LR had a slightly earlier age of onset of alcohol dependence (24.8 +/- 3.41 vs. 26.6 +/- 4.48 years), and this finding was unrelated to the presence of an alcohol-dependent father. Otherwise the members of the two groups demonstrated a similar course of alcohol dependence. There was no relationship between a low LR at age 20 and either the pattern of substances used or the rate of dependence on illicit drugs. CONCLUSIONS: The results indicate that for this sample a low LR to alcohol, while associated with a high risk for alcohol dependence, was not related to most aspects of the course of alcohol problems once dependence developed.

Adult↗
PubMed2001

A measure of the intensity of response to alcohol in a military population.

Heavy drinking and associated problems are relatively common in young men, including those in a military setting. This article explores characteristics of alcohol intake and associated difficulties and their relationship to a self-report of the usual intensity of response to alcohol in a sample of U.S. Marines. Two questionnaires related to demography and alcohol use histories, along with a simple, 12-item self-report measure of the usual number of drinks to experience an effect (the Self-Rating of the Effects of Alcohol, SRE) were administered to 1320 U.S. Marines. The sample had an average age of 22 years, 78% were Caucasian, and 92% were enlisted personnel. The relationships and correlations among drinking characteristics and problems and the usual number of drinks for an effect were determined. These subjects drank an average of 6 days per month, consuming an average of almost six drinks per drinking day, and reported more than three times per month in which they consumed six or more drinks per occasion. Consistent with studies of other populations, the SRE measures of intensity of response to alcohol showed a positive correlation with both drinking practices and problems, with the latter remaining significant even after controlling for recent drinking practices. The prodigious level of alcohol intake and associated problems, along with the SRE scores, indicate that the Marine Corps personnel are at especially high risk for alcohol-related life problems. These data also support the potential usefulness of the SRE both in identifying individuals likely to have more severe alcohol profiles and in educating individuals regarding their levels of risk for alcohol abuse and dependence.

Adult↗
PubMed2001

Five-year clinical course associated with DSM-IV alcohol abuse or dependence in a large group of men and women.

OBJECTIVE: The prognostic validity of the DSM-IV diagnoses of alcohol abuse and alcohol dependence was evaluated by examining the 5-year clinical course associated with those diagnoses in a large group of predominantly blue-collar men and women. METHOD: Personal semistructured interviews were carried out 5 years after an initial evaluation with 1,346 (75%) of the approximately 1,800 men and women participating in the Collaborative Study on the Genetics of Alcoholism who were eligible for follow-up. RESULTS: About two-thirds of the 298 subjects with DSM-IV alcohol dependence at baseline maintained that diagnosis during the 5-year study period. Fifty-five percent of the 288 subjects with DSM-IV alcohol abuse at baseline continued to meet one or more of the 11 DSM-IV abuse/dependence criteria, and 3.5% went on to meet the criteria for dependence at follow-up. Among the 760 subjects with no alcohol diagnosis at baseline, 2.5% met the criteria for alcohol dependence and 12.8% for alcohol abuse at follow-up. Baseline characteristics that predicted the occurrence of any of the 11 DSM-IV abuse/dependence criteria during the 5-year interval included male gender, lack of marital stability, presence of several of the criteria for dependence, and history of illicit drug use. CONCLUSIONS: 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.

Adult↗
PubMed2001

Correlates of unpredicted outcomes in sons of alcoholics and controls.

OBJECTIVE: Several risk factors for alcohol abuse and dependence have been identified, including a family history of the disorder and a low response to alcohol. However, not everyone with these attributes develops an alcohol use disorder and some alcoholics have neither characteristic. This article evaluates factors that might have contributed to unexpected outcomes, in a prospective study of sons of alcoholics and controls. METHOD: 411 men with complete data at baseline (Time 1 or T1) and at 15-year (Time 15 or T15) follow-ups were studied using the level of response (LR) to alcohol, the family history (FH) of alcoholism, and additional alcohol and drug-related experiences at T1. T15 data included the development of alcohol abuse or dependence, along with the 15-year functioning in six domains for the subject, as well as the characteristics of his spouse. The men were divided into groups based on the presence of two major risk factors, low LR and FH, after controlling for several other characteristics, including antisocial personality disorder. RESULTS: Rates of alcohol use disorders increased across Group 1 (family history negative [FHN] and no low LR), Group 2 (either family history positive [FHP] or low LR, but not both) and Group 3 (both FHP and low LR). After controlling for FH and LR for Group 1, only T1 drinking quantity and T15 positive alcohol expectancies related to a diagnosis, but explained only 12% of the variance. The results improved to R2's of 0.26 and 0.36 for Groups 2 and 3, with additional predictors including the T1 history of alcohol problems and T15 measures of poor coping mechanisms, higher drinking in the environment and less nurturance in the social support system. CONCLUSIONS: Procedures aimed at discouraging earlier heavier drinking, altering attitudes toward alcohol early in life, teaching appropriate coping methods and developing support systems might help individuals carrying multiple risk factors to become more resilient.

Adaptation, Psychological↗
PubMed2001

A preliminary evaluation of the potential usefulness of the diagnoses of polysubstance dependence.

OBJECTIVE: The concept of polysubstance dependence (PD) has been defined several ways over the years. However, few clinicians and researchers appear to use this label in a manner consistent with any of the major diagnostic manuals. This article evaluates the prevalence and characteristics associated with PD in participants in a large collaborative study. METHOD: In DSM-IV, PD characterizes people who do not meet criteria for dependence on any one substance but, when all drugs of abuse are considered have experienced three or more of the seven dependence items across the substances. In this study, structured face-to-face interviews were administered to 8,834 men and women as part of the Collaborative Study on the Genetics of Alcoholism. The 198 subjects (2.2%) with a slightly expanded concept of the DSM-IV disorder were compared with men and women with dependence on alcohol, marijuana or stimulants, subjects with substance abuse and those with no substance use disorder. RESULTS: In this dataset, compared with subjects with a specific substance dependence, those with PD were slightly more educated and less likely to be divorced or separated, and they had fewer substance-related problems. At the same time, those with PD had more substance problems than did subjects who only met criteria for abuse. These basic conclusions were unchanged among the subset of 59 subjects who met the more restricted, classical DSM-IV PD criteria. CONCLUSIONS: The data indicate that, while relatively rare, subjects with PD might differ in potentially important ways from those with dependence or abuse on specific drugs. A large prospective study of a group with carefully defined PD is needed.

Adult↗
PubMed2001

A comparison of correlates of DSM-IV alcohol abuse or dependence among more than 400 sons of alcoholics and controls.

BACKGROUND: Alcohol dependence and abuse are defined as separate disorders. However, relatively few data are available about whether the same characteristics predict both syndromes. METHODS: Complete data were available from the 15 year follow-up of 411 men who originally had been evaluated from a university population at about age 20. Both baseline data gathered prospectively and the retrospective ratings in six domains of life functioning were analyzed for their relationship to the development of alcohol abuse or dependence during the follow-up. RESULTS: Baseline characteristics of a family history of substance use disorders, the quantity and frequency of drinking, the history of alcohol-related problems, and the level of response to alcohol all predicted future alcohol abuse or dependence, but only an alcoholic second-degree relative or a first-degree drug-dependent family member differentially predicted dependence. Logistic regression analyses revealed that similar baseline characteristics combined to predict dependence and, separately, abuse. When the domains of functioning during the 15 years were included, positive alcohol expectancies, poor coping mechanisms, low level of social support, and drinking in the environment contributed to both dependence and abuse, although the relationship was stronger for dependence. CONCLUSIONS: The predictors and correlates of alcohol abuse and dependence in this group of men were similar. Further research in additional populations and on other drugs is needed to determine if the two syndromes overlap sufficiently to be combined.

Adult↗
PubMed2001

A genome-wide search for genes that relate to a low level of response to alcohol.

BACKGROUND: The low level of response (LR) to alcohol is genetically influenced in both humans and animals, and a low LR is a characteristic of offspring of alcoholics that has been reported to predict alcoholism 10 and 15 years later. The genes that contribute to a low LR have not yet been identified. METHODS: A 12-item questionnaire that measures LR, the Self Rating of the Effects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genetic material was available. These subjects were genotyped by using 336 markers with an average heterozygosity of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and qualitative nonparametric, sib-pair analyses were carried out for the SRE measure related to early drinking experiences. RESULTS: Correlations of SRE scores across related individuals were significant and between 0.16 and 0.22 for most values, compared with nonsignificant correlations of 0.03 or less among unrelated individuals. Linkage analyses performed by using the FIRST 5 variables (first five times alcohol is consumed) identified four chromosomal regions with lod scores > or = 2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample. CONCLUSIONS: These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon.

Alcoholism↗
PubMed2000

Family-based study of the association of the dopamine D2 receptor gene (DRD2) with habitual smoking.

A recent study showed an association between the dopamine D2 receptor gene (DRD2) and smoking. The purpose of this study was to determine if the familial transmission of smoking is linked to variation at the DRD2 locus in a genetically informative sample. Subjects were identified in alcohol treatment centers and their relatives were recruited for study. All subjects were interviewed to assess alcohol dependence, smoking habits, and psychiatric disorders. Two polymorphisms within the DRD2 gene were analyzed, including the TaqIA polymorphism. The sample consisted of 138 nuclear families with at least one offspring with habitual smoking, and analysis was by the transmission disequilibrium test (TDT), which avoids problems due to population stratification. There was no significant difference in the frequency between DRD2 alleles transmitted and not transmitted to habitual smokers. There also was no evidence for unequal transmission of DRD2 alleles for the phenotypes "ever smoker" or comorbid alcohol dependence and habitual smoking. This study does not support linkage of the DRD2 with smoking.

Chromosome Mapping↗
PubMed2000

A latent class analysis of antisocial personality disorder symptom data from a multi-centre family study of alcoholism.

AIMS: To determine if there are subtypes of Antisocial Personality Disorder (ASPD), as manifested by distinctive symptom profiles or by associations with alcohol, other drug dependence or other psychiatric disorders. METHODS: Data on 38 symptoms of ASPD (including childhood conduct disorder) obtained from probands, their relatives and controls (2834 females and 3488 males) recruited for the Collaborative Study on the Genetics of Alcoholism (COGA) were analyzed using latent class analysis. Associations of the resulting latent classes with alcohol dependence (AD) and other psychiatric disorders were examined. FINDINGS: Among women, a 4-class solution was obtained in which conduct disorder and ASPD were found almost exclusively in the most severely affected class with two additional classes with mild and moderate behavior problems also identified. A strong linear trend (p < 0.001) for AD was observed, with each successive class manifesting a higher prevalence than the previous class. Milestones of drinking careers and dependence on other drugs also showed a strong association with class severity. Among men, a 5-class solution was obtained and, like women, the highest prevalence of ASPD (74.6%) was found in the most severely affected class. Somewhat unexpected was the observation that prevalence of AD was equivalent in the two most severe classes. The data for men indicated a class with a milder spectrum of childhood misbehaviors but with an adult ASPD profile--as well as other psychiatric co-morbidity--that was comparable to the most severe class. CONCLUSIONS: Overall, findings from both men and women did not support the existence of subtypes of ASPD, but rather indicated a disorder distributed on a severity spectrum.

Adult↗
PubMed2000

Genetics of the risk for alcoholism.

This paper reviews the literature on the importance of genetic influences in the development of alcohol abuse and dependence (alcoholism). The alcohol use disorders are fairly typical of most complex genetic conditions in that multiple genetic influences combine together to explain approximately 40% to 60% of the risk. One useful approach for identifying specific genes related to alcoholism involves identifying a population in which known genetic factors are controlled and using genome scan and/or case-control, association approaches to search for specific genes. Several characteristics, or endophenotypes, have been identified as both genetically influenced and contributing toward the risk for alcoholism, including alcohol-metabolizing enzymes, the low level of response to alcohol, and electrophysiological measures. The potential importance of each of these characteristics is reviewed, and data relating to the search for specific genetic material for each endophenotype are presented. These findings are placed in the perspective of the impact that they are likely to have on both prevention and treatment efforts in the alcohol field.

Alcoholism↗
PubMed2000

Behavioral symptoms and psychiatric diagnoses among 162 children in nonalcoholic or alcoholic families.

OBJECTIVE: People with alcoholic relatives have high rates of alcohol abuse and dependence as adults, but their patterns of problems earlier in life are less clear. Many studies have not controlled for parental disorders other than alcoholism or for parents' socioeconomic status and general life functioning. The authors' goal was to conduct a study controlling for such factors. METHOD: Personal structured interviews and a behavioral checklist were administered to the parents of 162 children 7 years old or older whose fathers had participated in the 15-year follow-up of 453 sons of alcoholics with no history of antisocial personality disorder and sons of nonalcoholic comparison subjects originally selected from a university population. RESULTS: There was no significant relationship between a family history of alcoholism and childhood diagnoses of conduct, oppositional, or attention deficit disorders or with behavioral checklist summary scores. However, children with alcoholic relatives apparently have a slightly higher risk for drug abuse or dependence than those without alcoholic relatives. CONCLUSIONS: Once familial antisocial disorders and familial socioeconomic status are controlled for, a family history of alcoholism does not appear to relate to childhood externalizing disorders.

Adolescent↗
PubMed2000

The 5-year clinical course of high-functioning men with DSM-IV alcohol abuse or dependence.

OBJECTIVE: One goal of diagnostic criteria is to predict the course of clinically relevant future problems. This study evaluated the ability of the DSM-IV categories of alcohol abuse and alcohol dependence to predict the onset and cessation of the 11 DSM-IV abuse/dependence criterion items. METHOD: The DSM-IV categorical approach was used to determine alcohol diagnoses for 435 highly educated young adult men, who constituted 97.3% of the 447 men appropriate for this study. Structured face-to-face follow-up interviews were administered 5 years later. RESULTS: At the beginning of the study, 14.5% (N=63) of the subjects were alcohol dependent, 18.2% (N=79) reported alcohol abuse, and 67.4% (N=293) carried no alcohol diagnosis. Across these three diagnostic groups, 68.3%, 46.8%, and 15.4%, respectively, experienced at least one of the 11 DSM-IV abuse/dependence criterion items over the next 5 years. Only 11.4% of those who reported alcohol abuse went on to develop alcohol dependence. In addition to their diagnosis, characteristics that predicted subsequent problems with alcohol included a family history of alcoholism, higher levels of alcohol intake and a greater number of alcohol problems in the 10 years preceding the diagnosis, and a history of drug use. CONCLUSIONS: Even in this highly educated and high-functioning group of men, alcohol abuse and dependence predicted the onset and cessation of alcohol-related problems.

Adult↗
PubMed2000

Clinical characteristics and family histories of alcoholics with stimulant dependence.

OBJECTIVE: While much is known about the clinical patterns and family histories of individuals with alcoholism or stimulant (cocaine and amphetamine) dependence, there are few data that describe men and women with concomitant alcohol and stimulant dependence. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism, structured interviews were administered to 3,882 (2,432 male) DSM-III-R defined alcohol and/or stimulant dependent subjects. The characteristics and family histories of four groups were compared: Group 1 (26%), with the onset of alcohol before stimulant dependence; Group 2 (10%), with alcohol dependence simultaneously with or after stimulant dependence; Group 3 (58%), with alcohol dependence only; Group 4 (6%), with stimulant dependence only. RESULTS: Individuals with concomitant alcohol and stimulant dependence (Groups 1 and 2) reported more general life problems (e.g., marital instability), a higher rate of antisocial personality disorder and more substance-induced mood disorders, additional drug dependencies and substance-related difficulties than those with dependence on one substance only. People with alcohol dependence before stimulant dependence had the most severe clinical patterns. In addition, alcohol dependence and stimulant dependence were found to breed true in families of subjects with these concomitant disorders. The major findings were confirmed with logistic regression analyses, and were independent of ASPD and gender. CONCLUSIONS: It is important for clinicians to be aware of the severe clinical characteristics of patients with concomitant alcohol and stimulant dependence. In addition, the data consistent with drug-specific heritability in this heterogeneous population may be useful to researchers.

Adult↗
PubMed2000

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Alcoholism↗
PubMed2000

The relationships of a family history of alcohol dependence, a low level of response to alcohol and six domains of life functioning to the development of alcohol use disorders.

OBJECTIVE: Numerous biological and sociocultural factors have been proposed as potentially important to the risk for alcohol use disorders. This study evaluates the relationships to alcohol abuse or dependence of several additional potential trait and state characteristics when studied in the context of a family history of alcohol dependence (FH) and the level of response (LR) to alcohol. METHOD: Data were generated from the successful 15-year follow-up of 97% of 453 sons of alcohol dependent men and controls; of these, 315 men were appropriate for the current analyses. Personal interviews were used to gather data from the subjects and additional informants to study the relationships among FH, LR as determined 15 years previously, and retrospective ratings over the recent 15 years for six additional domains of life functioning. These were evaluated as correlates of a diagnosis of an alcohol use disorder in both a 3-step hierarchical and a 7-step structured series of regressions for the subjects with complete data. RESULTS: LR, FH and measures from all of the domains except stress had significant zero-order correlations with alcohol abuse or dependence. The hierarchical regression revealed that LR and FH remained significant when considered in the context of the five remaining domains. Both trait-like characteristics (behavioral undercontrol, alcohol expectancies and ways of coping) and state-like domains (nurturance in the social support system and the amount of drinking in the environment) added significantly to the analyses. A heuristic model of the relationship among these variables was tested in a structured series of regressions with a final R2 of 0.22. Future prospective study of the offspring of these subjects will help evaluate potential causal implications of these findings. CONCLUSIONS: Prospective studies, measuring both biological and environmental factors, are needed for optimal understanding of the performance of such characteristics in real-life conditions.

Adaptation, Psychological↗
PubMed1999

Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABA alpha 6 receptors and the serotonin transporter in the level of response to alcohol: a pilot study.

BACKGROUND: The vulnerability to alcohol dependence appears to be genetically influenced through a variety of mechanisms. One potentially genetically mediated channel may be a low level of response (LR) to alcohol, which has been seen in children of alcoholics and noted to predict future alcohol abuse and dependence. This pilot study uses a case and control genetic association approach to evaluate the possible role of five genotypes in both LR and alcoholism in informative subgroups of men with high and low LR scores documented 15 years earlier. METHODS: As part of a larger study, 41 men, about 39 years old, were selected from among the first 113, completed 15-year follow-ups in a prospective study. The 17 subjects whose LRs at age 20 were in the lower third were compared on five polymorphisms of four genes with 24 men whose reactions to alcohol had been above the median. RESULTS: The 14 men with the LL genotype of the serotonin transporter (5-HTT) polymorphism and the seven with the Pro/Ser genotype of the GABAA alpha 6 polymorphism had demonstrated lower LR scores at about age 20, and had significantly higher proportions of alcoholics than the other genotypes for those loci. All four subjects with combined LL and Pro/Ser genotypes had developed alcoholism and demonstrated the lowest LR scores overall. There was no evidence that two polymorphisms of the 5-HT2A receptor gene and one of the 5-HT2C receptor gene were related to LR or alcoholism in this sample. CONCLUSIONS: These results are consistent with animal and human studies suggesting a possible role for genetic variation in the GABAA alpha 6 and the serotonin transporter in the reaction to alcohol and the alcoholism risk.

Adult↗