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Biomedical subjects

M A Schuckit

Publications and source records attributed to M A Schuckit.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Co-occurring risk factors for alcohol dependence and habitual smoking.

Smoking and alcohol dependence frequently occur together, and both behaviors are determined in part by genetic influences. The Collaborative Study on the Genetics of Alcoholism (COGA), which is investigating the genetic factors contributing to alcohol dependence, also allows for analyses of the genetic factors determining smoking. Using a sample comprised of alcoholics and their closest (i.e., first-degree) relatives as well as a community-based control sample, COGA investigators found that both alcohol dependence and habitual smoking were transmitted within families. This familial transmission resulted from both common and drug-specific influences, which likely include genetic factors. Further genetic studies (i.e., candidate gene studies and genomic screening approaches) have identified several DNA regions that may contain genes that confer a susceptibility for alcoholism. Some of those genes also may contribute to the risk for habitual smoking.

Age Factors↗
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↗
PubMed1999

Clinical implications for four drugs of the DSM-IV distinction between substance dependence with and without a physiological component.

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.

Adult↗
PubMed1999

Characteristics of alcohol dependent subjects with very elevated levels of Gamma-Glutamyltransferase (GGT).

OBJECTIVE: This article examines characteristics of a subgroup of alcohol dependent men with very elevated serum Gamma-Glutamyltransferase (GGT) activity. METHOD: GGT was measured in 196 men soon after admission to an inpatient alcohol and drug treatment program. Subjects were split into two groups based on the a priori GGT value of > or =150 U/L for Group 1 (n = 20), and <150 U/L for Group 2 (n = 176). Serum aspartate amino-transferase (AST), serum alanine amino-transferase (ALT) and mean corpuscular volume (MCV), as well as several aspects of the drinking history, were compared cross-sectionally between the two groups. The stability of GGT in the context of drinking was evaluated prospectively over 12 months in a subsample of 35 individuals. RESULTS: Most measures of the drinking pattern and severity of dependence were similar between the two groups, although subjects in Group 1 demonstrated higher levels for AST (p < .01), MCV (p < .01) and ALT (p < .01). Subjects in Group 1 reported more drinking days per month (23.8 +/- 3.98 vs 17.8 +/- 8.71, t = 5.43, p < .001), and more related history of alcoholic liver disease (30.0% vs 8.5%, chi2 = 8.66, p < .01). In the presence of the variables significantly different between the two groups, AST, the number of drinking days per month and the proportion with alcoholic liver disease predicted membership to Group 1, although their influence was moderate (pseudo R between 0.16 and 0.20). The correlation between GGT at intake and follow-up in 35 individuals who returned to drinking was r = .56, p < .001, while two out of three subjects with high GGT at intake were also high at follow-up. CONCLUSIONS: Subjects with very high GGT seem to demonstrate a more intense vulnerability to alcohol, a characteristic which appears to be stable over time.

Adult↗
PubMed1999

Evaluation of the self-rating of the effects of alcohol form in Asian Americans with aldehyde dehydrogenase polymorphisms.

OBJECTIVE: In order to easily assess individual differences in response to alcohol, the Self-Rating of the Effects of Alcohol (SRE) form was recently developed and its psychometric properties tested in primarily white subjects. This study aimed to further evaluate the SRE in a population known to have genetically mediated variability in response to alcohol and risk for alcoholism, Asian Americans with ALDH2 polymorphisms. METHOD: Men and women of Chinese, Japanese or Korean heritage between the ages of 21 and 26 years (N = 156) completed the SRE and a blood sample was drawn for genotyping at the ALDH2 locus. RESULTS: SRE results were available from 137 (78 female) subjects. With the effects of gender, body weight, frequency of recent drinking and quantity of recent drinking controlled, ALDH2 genotype still accounted for a significant amount of variability in SRE score in this Asian-American sample. Evaluation of SRE scores 4.5 or higher indicated that a low response to alcohol was associated with ALDH2*1/2*1 genotype, male gender and Korean heritage, all factors associated with increased risk for alcoholism. CONCLUSIONS: These results provide additional support for the SRE as a valid instrument for assessing individual variability in response to alcohol and as a useful measure for identifying individuals at relatively increased or decreased risk for alcoholism based on level of reaction to alcohol.

Adult↗
PubMed1999

Clinical characteristics of alcoholism in alcohol-dependent subjects with and without a history of alcohol treatment.

BACKGROUND: Most clinical alcohol research is carried out on alcoholics who are in treatment, usually inpatients. However, most alcohol-dependent men and women never enter treatment, and even fewer ever receive inpatient care. Thus, some generally accepted data on the clinical course of alcoholism, derived from treatment samples, might not generalize to the entire population of alcohol-dependent individuals. This article characterizes the clinical characteristics of alcohol dependence in three groups of alcoholics, based on their histories of treatment for alcohol problems: those without prior rehabilitation; those with only outpatient approaches or Alcoholics Anonymous (AA); and subjects with an inpatient experience. METHODS: Semistructured interviews were administered to 3572 DSM-III-R-defined alcohol-dependent subjects from the Collaborative Study on the Genetics of Alcoholism. The clinical patterns were compared across the three groups of alcoholics: Group 1, never-treated (n = 1582; 44%); Group 2, histories of outpatient or AA only (n = 399; 11%); and Group 3, at least one inpatient experience (n = 1591; 45%). RESULTS: A progression was shown from Groups 1 to 3 for more general life problems (e.g., unemployment, marital instability); higher rates of additional drug dependencies and psychiatric disorders; and more alcohol-related adverse events. Logistic regression analyses revealed that those with no prior treatment were more likely to be women, Caucasian, and employed, and to report a lower rate of divorce/separation, lower levels of alcohol intake, and fewer alcohol problems. Among those who received help, inpatient care was predicted by an opposite profile. CONCLUSIONS: These results indicate that studies using data from inpatient populations may give a skewed picture of the clinical characteristics of alcohol dependence.

Adult↗
PubMed1999

Impact of a stimulant-focused enhanced program on the outcome of alcohol- and/or stimulant-dependent men.

BACKGROUND: The approaches to the treatment of most forms of substance dependence are similar. It is not clear whether specific treatment components need to be added to address specific substances. This study asks two questions: What is the impact of a more intense drug treatment program, and do different substance problems require different treatment interventions? METHODS: The 383 veterans included in this study represent two groups of consecutive inpatient male admissions with current alcohol dependence and/or dependence on amphetamines or cocaine at the inpatient Alcohol and Drug Treatment Program of the Veterans Affairs San Diego Healthcare System. All were interviewed at intake by trained interviewers using a standardized semistructured assessment instrument, and a resource person interview also was conducted with 85% of them. The first group of men received the Standard Treatment Program (STP), whereas the second group received the Enhanced Treatment Program (ETP). The latter included an addition of 10 hr per week of intense treatment aimed at stimulants, including two newly developed manual-driven groups (Relapse Prevention and Interpersonal Counseling), each of which met twice a week. RESULTS: The patient follow-up was 92% at 3 months and 83% at 12 months. Abstinence from substances of abuse for ETP and STP were 63% vs. 49% at 3 months and 43% vs. 24% at 12 months. Logistic regressions demonstrated that treatment type continued to predict outcome even in the context of other potentially predictive variables. CONCLUSIONS: Despite the ETP emphasis on stimulants, both alcohol- and stimulant-dependent men appeared to benefit, suggesting a generic improvement in substance use.

Adolescent↗
PubMed1998

Genome-wide search for genes affecting the risk for alcohol dependence.

Alcohol dependence is a leading cause of morbidity and premature death. Several lines of evidence suggest a substantial genetic component to the risk for alcoholism: sibs of alcoholic probands have a 3-8 fold increased risk of also developing alcoholism, and twin heritability estimates of 50-60% are reported by contemporary studies of twins. We report on the results of a six-center collaborative study to identify susceptibility loci for alcohol dependence. A genome-wide screen examined 291 markers in 987 individuals from 105 families. Two-point and multipoint nonparametric linkage analyses were performed to detect susceptibility loci for alcohol dependence. Multipoint methods provided the strongest suggestions of linkage with susceptibility loci for alcohol dependence on chromosomes 1 and 7, and more modest evidence for a locus on chromosome 2. In addition, there was suggestive evidence for a protective locus on chromosome 4 near the alcohol dehydrogenase genes, for which protective effects have been reported in Asian populations.

Adolescent↗
PubMed1998

Familial transmission of substance dependence: alcohol, marijuana, cocaine, and habitual smoking: a report from the Collaborative Study on the Genetics of Alcoholism.

BACKGROUND: Alcoholism and substance dependence frequently co-occur. Accordingly, we evaluated the familial transmission of alcohol, marijuana, and cocaine dependence and habitual smoking in the Collaborative Study on the Genetics of Alcoholism. METHODS: Subjects (n=1212) who met criteria for both DSM-III-R alcohol dependence and Feighner definite alcoholism and their siblings (n=2755) were recruited for study. A comparison sample was also recruited (probands, n=217; siblings, n=254). Subjects were interviewed with the Semi-Structured Assessment for the Genetics of Alcoholism. The familial aggregation of drug dependence and habitual smoking in siblings of alcohol-dependent and non-alcohol-dependent probands was measured by means of the Cox proportional hazards model. RESULTS: Rates of alcohol, marijuana, and cocaine dependence and habitual smoking were increased in siblings of alcohol-dependent probands compared with siblings of controls. For siblings of alcohol-dependent probands, 49.3% to 50.1% of brothers and 22.4% to 25.0% of sisters were alcohol dependent (lifetime diagnosis), but this elevated risk was not further increased by comorbid substance dependence in probands. Siblings of marijuana-dependent probands had an elevated risk of developing marijuana dependence (relative risk [RR], 1.78) and siblings of cocaine-dependent probands had an elevated risk of developing cocaine dependence (RR, 1.71). There was a similar finding for habitual smoking (RR, 1.77 in siblings of habitual-smoking probands). CONCLUSIONS: Alcohol, marijuana, and cocaine dependence and habitual smoking are all familial, and there is evidence of both common and specific addictive factors transmitted in families. This specificity suggests independent causative factors in the development of each type of substance dependence.

Adolescent↗
PubMed1998

Quantitative trait loci analysis of human event-related brain potentials: P3 voltage.

The P3 event-related brain potential (ERP) is a positive-going voltage change of scalp-recorded electroencephalographic activity that occurs between 300-500 ms after stimulus onset. It is elicited when a stimulus is perceived, memory operations are engaged, and attentional resources are allocated toward its processing. Because this ERP component reflects fundamental cognitive processing, it has found wide utility as an assessment of human mental function in basic and clinical studies. In particular, P3 attributes are heritable and have demonstrated considerable promise as a means to identify individuals at genetic risk for alcoholism. We have conducted a quantitative linkage analysis on a large sample from families with a high density of affected individuals. The analyses suggest that several regions of the human genome contain genetic loci related to the generation of the P3 component of the ERP, which are possible candidate loci underlying the functional organization of human neuroelectric activity.

Alcoholism↗
PubMed1998

Platelet monoamine oxidase activity in subgroups of alcoholics and controls: results from the Collaborative Study on the Genetics of Alcoholism.

OBJECTIVE: Platelet monoamine oxidase (MAO) B activity levels were evaluated to determine whether low platelet MAO activity is a marker for alcoholism, correlates of alcoholism (e.g., cigarette smoking), or a subtype of alcoholism. METHODS: Adult women (n = 788) and men (n = 685) participating in the Collaborative Study on the Genetics of Alcoholism study were evaluated with a semistructured interview, and blood samples were obtained for determination of platelet MAO activity using tryptamine (0.1 mM) as substrate. DSM-III-R alcohol-dependent individuals were subgrouped using four currently available methods (e.g., two variations of the type 1/type 2 scheme, primary versus secondary typology, type A/type B dichotomy). RESULTS: In the overall sample, subjects' gender, cigarette smoking status, and the Collaborative Study on the Genetics of Alcoholism site at which their platelets were prepared explained 22% of the variance in platelet MAO activity levels, and multivariate analysis showed that carrying a broad diagnosis of alcohol dependence did not uniquely explain any additional variance in platelet MAO activity levels. Furthermore, within each of the alcoholic subgrouping methods tested, there were no significant differences in platelet MAO activity for type 1 versus type 2, type A versus type B, or primary versus secondary alcoholics. CONCLUSIONS: Cigarette smoking and male gender are associated with decreased platelet MAO activity levels. After considering these factors, a diagnosis of alcohol dependence does not predict any additional variance in MAO-B activity. Phenotypes of alcoholics (e.g., type 1 versus type 2, type A versus type B, primary versus secondary) do not differ in platelet MAO activity. The results suggest that decreased platelet MAO activity is not a trait marker of alcoholism or one of its subtypes; but, rather, is a state marker of cigarette smoking.

Adult↗
PubMed1998

Clinical relevance of the distinction between alcohol dependence with and without a physiological component.

OBJECTIVE: DSM-IV indicates that diagnoses of substance dependence should be further characterized with regard to the presence of a physiological component, defined by tolerance or withdrawal. This study evaluated the possible meaning of this distinction in alcohol-dependent men and women. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism, structured interviews were carried out with 3,395 DSM-III-R-defined alcohol-dependent individuals divided into 2,949 subjects (86.9%) with evidence of tolerance and/or withdrawal (group 1), 51.3% of whom evidenced withdrawal symptoms, and 446 subjects (13.1%) without a physiological component (group 2). Data were evaluated to determine differences between the two groups. RESULTS: Group 1 reported greater severity of alcohol dependence as demonstrated by a larger maximum number of drinks in 24 hours, more persons reporting binges, more alcohol-related life problems, more relevant DSM-III-R criteria endorsed, more physiological complications, and more alcohol-related emotional/psychiatric symptoms such as depression and anxiety. Each of these severity indicators for problems in group 1 was significant in the presence of the others in a logistic regression, and similar items remained significant when tolerance alone, withdrawal alone, or their combination was used as the criterion for group 1 membership; however, for withdrawal a larger proportion of the variance was explained by the predictor variables. The regression results were independent of gender, proband status, and history of antisocial personality disorder. CONCLUSIONS: The results support the clinical relevance of distinguishing between alcohol-dependent patients with and without a physiological component. The data indicate a potential advantage to limiting that definition to withdrawal only.

Adult↗
PubMed1998

Biological, psychological and environmental predictors of the alcoholism risk: a longitudinal study.

OBJECTIVE: This article reviews results from an ongoing prospective study of 453 sons of alcoholics and controls, and presents new data from the 15-year follow-up. METHOD: Drinking, but not alcohol dependent, 20-year-old sons of alcoholics and controls were evaluated for their level of response (LR) to alcohol and were subsequently followed, through personal interviews, 10 years and 15 years later. RESULTS: The 10-year follow-up of 450 (99.3%) men and provisional analyses from the first 127 subjects at 15 years revealed that a low LR at about age 20 predicted subsequent alcoholism, even after considering the original quantity and frequency of drinking and six additional domains of influence. Regarding the latter, behavioral undercontrol and work stress appear to interact with LR, with alcohol expectancies, coping mechanisms and aspects of the drinking in the environment also appearing to add to the model, while other aspects of life stress and the social support network do not. CONCLUSIONS: The prospective evaluation of subjects at higher risk for alcoholism is a potentially powerful tool in identifying the relationships among a broad range of moderators and mediators of the alcoholism risk. The present tentative results based on the first 127 subjects are primarily heuristic as findings might change in the full sample. These data set the stage for completion of the 15-year follow-up and for a subsequent 20-year evaluation which will focus on the same domains in the projected almost 560 sons and daughters of the original sample.

Adaptation, Psychological↗