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Marc A Schuckit

Publications and source records attributed to Marc A Schuckit.

66 records · Page 4Linked to original sources
PubMed2002

Behavioral and functional neuroimaging evidence for prefrontal dysfunction in methamphetamine-dependent subjects.

Stimulant-dependent subjects show dysfunctions in decision-making similar to those seen in subjects with ventromedial prefrontal cortex lesions. Studies of drug craving, reward association, and decision-making have implicated dysfunctions of the dorsolateral and orbitofrontal cortex as a key neural substrate in subjects with stimulant dependence. Here, a functional magnetic resonance imaging (fMRI) study was carried out to determine the relationship between decision-making dysfunction and neural activation in different prefrontal areas. This investigation tested the behavioral hypothesis that methamphetamine-dependent subjects in early sustained remission show decision-making dysfunctions that are consistent with an increased reliance on stimulus-contingent response selection. It was hypothesized that these decision-making dysfunctions are due to differences in task-related activation in the dorsolateral and ventromedial prefrontal cortex. Ten methamphetamine-dependent subjects were compared with ten age- and education-matched controls performing a two-choice prediction task and a two-choice response task during a fMRI session. Response bias, latency, and mutual information measures assessing the underlying strategies of the decision-making sequences were obtained. First, methamphetamine-dependent subjects were more influenced by the immediately preceding outcome during the two-choice prediction task relative to normal comparison subjects. Second, methamphetamine-dependent subjects activated less dorsolateral prefrontal cortex (BA 9) and failed to activate ventromedial cortex (BA 10,11) during the two-choice prediction task compared with the two-choice response task. These results support the basic hypothesis that stimulant-dependent subjects exhibit fundamental cognitive deficits during decision-making that are consistent with both orbitofrontal and dorsolateral prefrontal dysfunction.

Adult↗
PubMed2002

Similarities in the clinical characteristics related to alcohol dependence in two populations.

This report evaluates whether the characteristics associated with alcohol abuse and dependence are similar in two groups of men despite their enrollment in different research projects and the resulting differences in education and related background variables. Data regarding demographic and substance use characteristics and problems were gathered using similar research instruments from the 15-ear follow-up of 108 highly educated DSM-III-R alcohol-dependent men from the San Diego Prospective Study (Group 1) and 306 similarly diagnosed men with lower education from the Collaborative Study on the Genetics of Alcoholism (COGA ) (Group 2). Both groups of alcoholics reported high rates of alcohol-relatedproblems, a similar maximum number of drinks per day, and similar proportions of drug use/non-use, although Group 1 subjects were less likely to report alcohol withdrawal and items associated with loss of control. Thus, teachers and clinicians may be able to generalize their knowledge and experience across different groups of alcoholics, using common sense modifications of their expectations based on the general characteristics of the groups involved despite differences in background variables, including education, income, marital status, and employment.

Adult↗
PubMed2002

Human alcoholism studies of genes identified through mouse quantitative trait locus analysis.

Coding region DNA sequence variants have been recently identified in several QTL candidate genes in a mouse model of differential sensitivity to alcohol [inbred long-sleep (ILS) and inbred short-sleep (ISS)]. This work has been extended into a human population characterized for their initial level of response to alcohol (LR). The coding region of one of the most promising of these candidate genes, zinc finger 133 (Znf133), has been sequenced completely in 50 individuals who participated in alcohol challenges at approximately age 20 and have been followed subsequently for the last 15 years. PCR products were obtained for the protein coding region of ZNF133 using human genomic DNA and directly sequenced using automated sequencers. Novel single nucleotide polymorphisms (SNPs) were detected by analyzing the sequence data using a suite of bioinformatics programs including Consed, Phred, Phrap and Polyphred. Five human SNPs were detected, two that correspond to amino acid changes in the protein, two that are silent DNA changes and one located in an intron. In this small sample, no significant association between any of the SNPs and alcohol diagnosis was detected. A follow-up of these SNPs in a larger sample should allow a more definitive conclusion to be reached. Significantly, the data presented here demonstrate the feasibility of directly testing genes in human alcoholic populations that had been identified first by comparative DNA sequencing of candidate genes located within mouse alcohol-related QTLs, even without detailed knowledge of the gene's function.

Adult↗
PubMed2002

The prevalence and clinical course of sedative-hypnotic abuse and dependence in a large cohort.

Relatively little is known about the prevalence and clinical characteristics of dependence on sedative-hypnotics, and almost nothing has been published regarding abuse. This report relates information on Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IIIR) sedative-hypnotic use disorders among subjects from the Collaborative Study on the Genetics of Alcoholism (COGA). A standardized interview was used to generate data on 407 men and women in Group 1 with sedative-hypnotic dependence (4.4% of the COGA sample), 34 in Group 2 with abuse (0.4%), and 3,426 comparison subjects in Group 3 with alcohol dependence in the absence of a sedative-hypnotic use disorder (36.7%). The remaining COGA subjects (48.5%) were not included as they had neither alcohol nor sedative-hypnotic dependence or abuse. Those with sedative-hypnotic abuse or dependence were more likely to be Caucasian individuals with abuse or dependence on marijuana, cocaine, amphetamines, or opioids. Subjects in Groups 1 and 2 were also more likely to have histories of independent major depressive and panic disorders, as well as substance-induced mood disorders. Those with dependence, compared to abuse, were likely to be women, reported staying intoxicated for a day or more, but noted less abuse of opioids or amphetamines, although Group 2 members also had high rates of difficulties with sedative-hypnotics. These results highlight notable rates of sedative-hypnotic dependence in the COGA families, and indicate that while sedative-hypnotic abuse does occur, and while the clinical course can involve relatively serious problems, it is less common than dependence.

Adult↗
PubMed2002

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.

Adolescent↗
PubMed2002

Women who marry men with alcohol-use disorders.

BACKGROUND: Women who marry men with alcohol-use disorders (AUDs) might have unique characteristics that could affect the clinical course of their partner's AUD and the risk for problems in the offspring. Most data available on spouses of such men come from subjects in treatment, which might bias results to more severely impaired individuals. Our data were gathered as part of a prospective study of an original sample of 453 sons of alcoholics and controls who were originally selected as students or nonacademic staff at a university. METHODS: Personal interviews were performed with 327 women who were married to men who had been personally evaluated on multiple occasions over the prior 15 years. The data compare characteristics of the 235 women (71.9%) whose husbands had never developed alcohol abuse and dependence with the 92 (28.1%) for whom these disorders had been documented. RESULTS: The women who married men with an AUD were less likely to be homemakers, were more likely to meet criteria for alcoholism (especially abuse) themselves, were more likely to report use of illicit substances, and to be current smokers. However, spouses of men with AUDs in this highly functional sample had no higher risk for other major psychiatric disorders and did not report a higher rate of alcohol abuse or dependence or psychiatric conditions in their parents. CONCLUSIONS: The results demonstrate increased risks for the use of illicit substances and for AUDs in women married to alcoholics, despite the overall high level of functioning of the sample. This information may be relevant to enhancing our understanding of the environment in which their offspring are being raised. The descriptive aspects of the work might also help researchers and clinicians working with alcoholic families.

Adult↗
PubMed2002

Suggestive linkage on chromosome 1 for a quantitative alcohol-related phenotype.

BACKGROUND: Alcohol dependence is a clinically and etiologically heterogeneous disorder. Accordingly, a variety of subtypes of alcohol-dependent individuals have been proposed, and multiple operational definitions of alcohol use, abuse, and dependence have been used in linkage analyses directed toward detecting genes involved in alcohol use and problems. Here, we develop quantitative phenotypes that characterize drinking patterns among both alcoholic and nonalcoholic subjects, and use these phenotypes in subsequent linkage analyses. METHODS: More than 9000 individuals from alcoholic and control families were administered a semistructured interview and personality questionnaire as part of the initial stage of the Collaborative Study on the Genetics of Alcoholism (COGA). A principal component analysis was conducted on items that captured many of the dimensions of drinking and related behaviors, including aspects of alcohol use, antisocial behavior and affective disturbance when drinking, and personality. Factor scores were computed for all individuals. Nonparametric linkage analyses were conducted on these factor scores, in the initial COGA sample consisting of 987 individuals from 105 extended families, and in a replication sample consisting of 1295 individuals from 157 extended families. RESULTS: Three factors were identified, accounting for 68% of the total variance. The most promising regions of linkage appeared for factor 2, on which higher scores indicate a later age of onset of regular drinking and higher harm avoidance. Chromosome 1 yielded consistent evidence of linkage in both samples, with a maximum lod score of 3.3 when the samples were combined for analysis. Consistent suggestion of linkage also was found to chromosome 15. CONCLUSIONS: Developing novel phenotypes that more accurately model the effect of influential genes may help efforts to detect genes involved in complex disorders. Applying principal component analysis in the COGA sample provided support for some regions of linkage previously reported in COGA, and identified other new, promising regions of linkage.

Alcoholism↗
PubMed2002

Alcohol abuse and dependence among U.S. college students.

OBJECTIVE: To estimate the prevalence of alcohol abuse and dependence among U.S. college students, and to identify characteristics associated with these diagnoses. METHOD: More than 14,000 students at 119 4-year U.S. colleges completed a questionnaire that included items corresponding to DSM-IV diagnostic criteria for alcohol abuse and dependence. Frequencies were computed, and correlations used to identify demographic, drinking and other variables associated with these diagnoses. RESULTS: 31% percent of students endorsed criteria for an alcohol abuse diagnosis and 6% for a dependence diagnosis in the past 12 months. More than two of every five students reported at least one symptom of abuse or dependence. Students who were heavy episodic drinkers were more likely than those who were not to have an alcohol disorder. Students who were frequent heavy episodic drinkers had 13 times greater odds for abuse and 19 times greater odds for dependence. One of every five heavy episodic drinkers was classified with dependence. Few reported seeking treatment since coming to college. Students from heavy drinking college environments were more likely to have abuse and dependence diagnoses. CONCLUSIONS: Many college students report behaviors and symptoms that meet the diagnostic standard for alcohol abuse or dependence. In addition to strengthening prevention programs, colleges should implement new strategies for screening and early identification of high risk student drinkers and ensure that treatment is readily available for those with alcohol disorders.

Adolescent↗
PubMed2002

The importance of a positive family history of alcoholism, parental rejection and emotional warmth, behavioral problems and peer substance use for alcohol problems in teenagers: a path analysis.

OBJECTIVE: The purpose of this study was to test a hypothetical model of alcohol problems in German adolescents. Among 180 offspring, family history of alcoholism, parenting styles, behavioral and emotional problems, peer-group characteristics, feelings of self-esteem, behavioral problems and psychiatric comorbidity of the parents were examined. METHOD: Data were generated from the Study of Health in Pomerania (SHIP), in which families were randomly selected if 12-18 year old biological offspring were members of the household; a smaller group of subjects was selected from local outpatient treatment centers. Members of 133 families, including 180 (50.6% male) offspring who were appropriate for the current analyses, received personal semistructured diagnostic interviews and several self-rating questionnaires. Analyses compared offspring with alcohol problems (AP; n = 40) and with no alcohol problems (NAP; n = 140), and used structural equation modeling to test a hypothetical model. RESULTS: The comparisons revealed that the AP group had significantly more behavioral problems (e.g., aggression/delinquency), more perceived parental rejection and less emotional warmth, a higher amount of alcohol consumption, were more likely to associate with substance-using peers and more often received a diagnosis of conduct disorder or antisocial personality disorder. Whereas the family history of alcoholism did not differ significantly between groups, parents of offspring with an alcohol use disorder had significantly more additional diagnoses on DSM-IV Axis I. The evaluation of the model supported the importance of aggression/delinquency and association with substance-using peers for alcohol problems in people. An additional diagnosis in the parents was directly and indirectly (through aggression/delinquency) related to alcohol problems of the adolescents. CONCLUSIONS: The data indicate that alcohol problems in the offspring are associated with several domains of influence in their environment. Prospective studies measuring both biological and environmental factors using sufficient sample sizes will be needed for optimal understanding of the development of alcohol problems in youth.

Adolescent↗
PubMed2002

Defining alcohol-related phenotypes in humans. The Collaborative Study on the Genetics of Alcoholism.

Alcoholism is a disease that runs in families and results at least in part from genetic risk factors. The Collaborative Study on the Genetics of Alcoholism (COGA) is a Federally funded effort to identify and characterize those genetic factors. The study involves more than 1,000 alcoholic subjects and their families, with researchers conducting comprehensive psychological, physiological, electrophysiological, and genetic analyses of the participants. These analyses have identified several traits, or phenotypes, that appear to be genetically determined, such as the presence of alcohol dependence, the level of response to alcohol, the presence of coexisting depression, or the maximum number of drinks a person consumes per occasion. Genetic analyses have identified regions on several chromosomes that are associated with these phenotypes and need to be studied further.

Alcoholism↗
PubMedDate not supplied

Correlates of externalizing symptoms in children from families of alcoholics and controls.

AIMS: This paper describes a new stage in the ongoing evaluation of the original families of sons of alcoholics and controls where we now focus on the relationships among relevant domains of functioning in their young sons and daughters. METHODS: The data were gathered from the 15-year follow-up of the families of the original probands (the fathers of these offspring) who had been selected from among students and non-academic staff at a university at approximately age 20. At the 15-year evaluation of these families, a structured interview and the Child Behavioral Checklist (CBCL) questionnaire were administered to a parent, usually the mother, of 145 offspring age seven through 17. The eight domains evaluated here included the extended family histories of alcohol use disorders, parental alcoholism, independent mood or anxiety disorders in the grandparents and parents, the history of potential brain insults early in life, the absence of a biological parent in the home, and scores for internalizing symptoms, with externalizing symptoms as the dependent variable. RESULTS: Correlations among the domains were all in the predicted direction, a structural equation model revealed empirical results with an R(2) of 0.26, and there were high goodness of fit characteristics for hypothesized and empirical models. The results were similar for boys and girls and older versus younger offspring. CONCLUSIONS: An understanding of the relationships among characteristics in the offspring of the original probands offers the opportunity of establishing levels of functioning in relevant domains before the onset of alcohol-related problems or related disorders. The data presented here represent a baseline upon which future follow-ups will evaluate substance-related problems and disorders as this population matures.

Adolescent↗