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Marc A Schuckit

Publications and source records attributed to Marc A Schuckit.

At least 55 records · Page 3Linked to original sources
PubMed2004

Linkage and linkage disequilibrium of evoked EEG oscillations with CHRM2 receptor gene polymorphisms: implications for human brain dynamics and cognition.

Event-related oscillations (ERO) offer an alternative theoretical and methodological approach to the analysis of event-related EEG responses. The P300 event-related potential (ERP) is elicited through the superposition of the delta (1-3 Hz) and theta (3-7 Hz) band oscillatory responses. The cholinergic neurotransmitter system has a key function in modulating excitatory post-synaptic potentials caused by glutamate, and therefore influences P300 generation and the underlying oscillatory responses. Here we report significant linkage and linkage disequilibrium between target case frontal theta band, visual evoked brain oscillations and a single nucleotide polymorphism (SNP) from the cholinergic muscarinic receptor gene (CHRM2) on chromosome 7. We also demonstrate significant linkage disequilibrium between CHRM2 SNPs and target case parietal delta band visual evoked oscillations (LD P<0.001). These findings were not observed for the equivalent non-target case data, suggesting a role for the CHRM2 gene in higher cognitive processing in humans.

Adolescent↗
PubMed2004

The relationship between parental alcoholism and adolescent psychopathology: a systematic examination of parental comorbid psychopathology.

The relationship between parental alcohol dependence (with and without comorbid psychopathology) and adolescent psychopathology was examined in a sample of 665 13-17 year-old adolescents and their parents. Results indicated that adolescents who had parents diagnosed with alcohol dependence only did not significantly differ from adolescents who had parents with no psychopathology in regard to any of the measures of psychological symptomatology (substance use, conduct disorder, and depression) or clinical diagnoses (alcohol dependence, marijuana dependence, conduct disorder, or depression) assessed. In contrast, adolescents who had parents diagnosed with alcohol dependence and either comorbid drug dependence or depression were more likely to exhibit higher levels of psychological symptomatology. In addition, adolescents who had parents diagnosed with alcohol dependence, depression, and drug dependence were most likely to exhibit psychological problems. These findings underscore the importance of considering parental comorbid psychopathology when examining the relationship between parental alcoholism and offspring adjustment.

Adolescent↗
PubMed2004

The search for genes contributing to the low level of response to alcohol: patterns of findings across studies.

BACKGROUND: Alcoholism is a complex genetically influenced disorder in which multiple phenotypes [e.g., disinhibition, alcohol-metabolizing patterns, and the low level of response (LR) to alcohol] contribute to the risk. A low LR to alcohol is one of the more thoroughly studied risk phenotypes; data indicate that LR relates to the risk status, predicts future alcoholism, and has a heritability as high as 60%. This article reviews data from animal and human studies regarding the LR to alcohol, searching for a convergence of results that might lead to the identification of relevant genes. METHODS: A literature search was performed regarding animal and human genetic studies focusing on genes that might affect the LR to alcohol as a risk factor for alcoholism. The goal was to synthesize these results and highlight potential patterns. RESULTS: Focusing on both genetic linkage and association studies, a number of chromosomal regions and genes potentially relevant to findings across two or more sources were identified. The genes of potential interest fell into several categories, including second-messenger systems (e.g., G proteins, adenylyl cyclase, and protein kinases); neurotransmitters or drug-related receptors (e.g., gamma-aminobutyric acid-A, glutamate, serotonin, and cannabinoid and opioid receptors); genes that affect alcohol metabolism; and genes that might relate to an overlap in the risk for alcoholism and some psychiatric conditions (e.g., catechol-O-methyltransferase regarding schizophrenia and bipolar disorder). CONCLUSIONS: The review identifies several genes that may contribute to a low LR to alcohol and, thus, to an increased risk for alcohol use disorders. The chromosomal regions and genes highlighted here may form the basis for more focused genetic studies of alcohol use disorders, with the goals of developing more specific and effective prevention and treatment approaches.

Alcohol Drinking↗
PubMed2004

Findings across subgroups regarding the level of response to alcohol as a risk factor for alcohol use disorders: a college population of women and Latinos.

BACKGROUND: The rates of alcohol dependence, a genetically influenced disorder, are increased among Latino men in the United States and are lower among women across ethnic groups. These analyses explored whether the differential rate of alcohol use disorders (AUDs) might reflect one genetically influenced phenotype related to alcoholism risk: the low level of response (LR) to alcohol. METHODS: A questionnaire was mailed to students at two universities to identify drinking but not alcohol-dependent 18- to 29-year-old men and women who had a parent with alcohol dependence. Subjects were subsequently screened with a validated semistructured interview to corroborate the personal and family histories, and they participated in a challenge with alcohol 0.75 ml/kg for women and 0.90 ml/kg for men. LRs to alcohol were determined and compared between genders and between Latino versus Caucasian/Anglo subjects. RESULTS: The data revealed no consistent significant differences between genders regarding either subjective feelings of intoxication or alcohol-induced changes in body sway. A similar lack of differential between groups was observed when Latino and Caucasian/Anglo subjects were compared. However, there was at least a statistical trend for interactions when gender, ethnicity, and time were considered together; there was some evidence for a higher LR in Latina women. Perhaps reflecting the different weights and doses of alcohol used, men demonstrated higher breath alcohol concentrations, but no differences in these values were noted between Latino and Anglo populations. CONCLUSIONS: The results indicate that the LR to alcohol is not likely to explain differences in rates of AUDs between genders or these two ethnic groups overall. The possibility that a higher LR might be seen for the subgroup with the lowest AUD rate--Latina women--will require replication in larger samples of well matched groups before definitive conclusions can be drawn.

Adolescent↗
PubMed2004

Testing the level of response to alcohol: social information processing model of alcoholism risk--a 20-year prospective study.

BACKGROUND: The low level of response (LR) to alcohol is a genetically influenced characteristic associated with an enhanced risk for alcohol use disorders (AUDs). An optimal understanding of how this intermediate phenotype relates to the AUD risk requires evaluation of the milieu in which LR operates, and this study tested an LR/social information processing model in adult men. METHODS: Almost 300 Caucasian males (97% of those eligible, to date) from the San Diego Prospective Study participated in an alcohol challenge at approximately age 20 and were evaluated with a structural equation model regarding their expectations of the effects of alcohol, drinking among peers, use of alcohol to cope with stress, and alcohol-related problems during follow-up. RESULTS: The direct paths in the structural equation model in these 40-year-old men explained 58% of the variance of the alcoholic outcome at age 40 and 35% at age 35 while demonstrating good fitness characteristics. The LR to alcohol was related to the family history of AUDs and to the alcoholic outcome; the latter primarily operated through the use of alcohol to cope with stress. Although drinking in peers and expectations of the effects of alcohol both contributed to the model in these 40-year-old men, they were not directly related to LR. CONCLUSIONS: The results continue to support the importance of the low LR to alcohol as a predictor of AUDs, even when evaluated in the context of additional relevant characteristics. Future evaluations of adolescent and young adult subjects will also explore the potential importance of expectations of the effects of alcohol and drinking among peers as mediators or moderators of alcoholism risk among subjects with a low LR.

Adaptation, Psychological↗
PubMed2004

EEG alpha and level of response to alcohol in Hispanic- and non-Hispanic-American young adults with a family history of alcoholism.

OBJECTIVE: A person's level of response to alcohol is associated with family history of alcoholism, ethnic heritage and electroencephalogram (EEG) phenotype. The present study's aims were to investigate EEG alpha and response to alcohol in Hispanic-American and non-Hispanic-American young adults. METHOD: EEG power in the slow and fast alpha frequency ranges (7.5-9 Hz, 9-12 Hz) was obtained at baseline and at 74 minutes following the administration of alcohol to Hispanic-American (n = 79) and white non-Hispanic-American (n = 208) young adult men and women (18-25 years old), all of whom had a family history but no personal history of alcohol dependence. Measures of breath alcohol concentrations and subjective responses to alcohol (Subjective High Assessment Scale [SHAS]) also were ascertained. RESULTS: Alcohol was found to produce significant effects on EEG power in the slow (F = 79.5, p < .0001) alpha frequency range. Although no overall effects of alcohol were found in the fast alpha frequency range, Hispanic participants had decreases in EEG fast alpha activity following alcohol administration, whereas non-Hispanics had alcohol-induced increases in power in this frequency range (F = 4.0, p < .04). EEG power, in the fast alpha frequency range (9-12 Hz) at baseline, also was found to be negatively associated with level of response to alcohol, as indexed by SHAS scores (F = 5.2, 2/283 df, p < .023). CONCLUSIONS: Previous studies in Native Americans, Asians and Euro-Americans have suggested genetic stratification in EEG response to alcohol as well as significant associations with family history of alcoholism. The present results extend previous studies to Hispanics and further confirm that increased EEG alpha power at baseline is predictive of a less intense response to alcohol, as indexed by the SHAS.

Adolescent↗
PubMed2004

Patterns of drug-related disorders in a prospective study of men chosen for their family history of alcoholism.

OBJECTIVE: Alcohol use disorders (AUDs) and abuse or dependence on illicit substances often co-exist. Most studies evaluating these phenomena have focused on less well-educated individuals, using cross-sectional designs. This study controls for several factors that might contribute to a propensity toward both alcohol and substance-related conditions in a prospective follow-up of middle-class men. METHOD: The subjects (N = 249) were white sons of alcoholics and controls, followed for 20 years using structured interviews. They were evaluated at baseline and again 10, 15 and 20 years later. RESULTS: One in five subjects developed an illicit substance-related disorder by the 20-year follow-up, most commonly abuse or dependence on cannabinoids and/or stimulants. The men with these diagnoses were more likely to be recent smokers, to also fulfill criteria for alcoholism and to have a family history of a stimulant use disorder. They were not more likely to have family histories of alcoholism, did not have a lower response to alcohol at age 20 and had no enhanced risk for independent psychiatric disorders, although they did have relatives with manic depressive disease. CONCLUSIONS: Disorders related to illicit substances were common in this well-educated, highly functional population. Substance-related comorbidity with alcoholism did not seem to reflect several factors known to predict AUDs (e.g., family history of alcoholism and a low response to alcohol). The diagnostic overlap between AUDs and illicit substance-related disorders might reflect concomitant family histories of alcoholism and substance-related conditions and, perhaps, family histories of manic depressive disease.

Adult↗
PubMed2004

Level of response to alcohol and brain response during visual working memory.

OBJECTIVE: This study examined neural correlates of the low level of response to alcohol using functional magnetic resonance imaging (FMRI) during a challenging visual working memory task. METHOD: Participants were healthy adolescents (N = 35) with a range of drinking patterns recruited from local high schools. After a minimum 5 days of abstinence from alcohol and other drugs, FMRI, neuropsychological testing and the Self-Rating of the Effects of Alcohol were administered. RESULTS: Self-report of initial level of response to alcohol was significantly predicted by FMRI blood oxygen level dependent (BOLD) response to the visual working memory task in the right prefrontal and bilateral anterior cingulate region (12% of unique variance, p < .05) and right cerebellum and parahippocampal gyrus (17% of unique variance, p < .01), above and beyond effects accounted for by drinks consumed per month, age, gender and ethnicity. CONCLUSIONS: Young people who report having needed more alcohol to achieve specific effects during early drinking experiences show higher levels of brain response during visual working memory, perhaps suggesting less capacity to adjust cognitive processing to contextual demands.

Adolescent↗
PubMed2004

Parental substance use consequences and adolescent psychopathology.

OBJECTIVE: This study examines the relationship between parental substance use consequences and adolescent psychological problems by gender of the adolescent and gender of the parent. METHOD: The data in this study were collected between 1989 and 1994 from 173 (116 proband and 57 control) families participating in the Collaborative Study on the Genetics of Alcoholism (COGA) project. All 173 adolescents (89 [51%] boys) completed the Structured Assessment Record of Alcoholic Homes (SARAH) to assess parental substance use consequences. In addition, the Semi-Structured Assessment for the Genetics of Alcoholism for Adolescents (C-SSAGA-A) was administered to all adolescents to obtain clinical psychiatric diagnoses. RESULTS: Concern about mother's substance use was significantly associated with adolescent alcohol dependence and major depressive disorder. In addition, concern about father's substance use was significantly related to adolescent alcohol dependence. Avoidance of mother when she was drinking or using drugs and maternal anger when drinking or using drugs also was significantly associated with adolescent alcohol dependence, conduct disorder and major depressive disorder. In contrast, avoidance of father and paternal anger when drinking or using drugs was not related to any of the adolescent diagnoses. CONCLUSIONS: These results suggest that maternal substance use consequences may be more closely linked to adolescent psychological adjustment than are paternal substance use consequences.

Adolescent↗
PubMed2003

Decision making by methamphetamine-dependent subjects is associated with error-rate-independent decrease in prefrontal and parietal activation.

BACKGROUND: One important aspect in decision making is how success or failure influences the selection of a response. In a previous investigation, methamphetamine-dependent subjects (MD) selected win-stay/lose-shift consistent responses than normal comparison subjects (NC), which may imply that MD are more influenced by success. This study examined whether the degree of success and the degree of predictability differentially affected MD's decision making. METHODS: Using functional magnetic resonance imaging, 14 MD were compared with 14 NC while performing the two-choice prediction task at three success rates and the two-choice response task. RESULTS: The increase in win-stay/lose-shift consistent responses by MD relative to NC was independent of success rate. Irrespective of success, MD showed less task-related activation in orbitofrontal cortex (Brodmann's area [BA] 10), dorsolateral prefrontal cortex (BA 9), anterior cingulate (BA 32), and parietal cortex (BA 7). Whereas NC showed success-related patterns of neural activation in the orbitofrontal, dorsolateral prefrontal, and parietal cortex, MD showed activation that was highest when the outcome was most unpredictable. CONCLUSIONS: Our results are consistent with the hypothesis of a more rigid stimulus-response relationship during MD's decision making, which may be due to a shift from processing "success" toward processing the degree of stimulus "predictability."

Adult↗
PubMed2003

Association of GABA(A) receptors and alcohol dependence and the effects of genetic imprinting.

GABA receptor genes have been postulated as candidates affecting the risk for alcoholism. The potential association between genes encoding five subunits of the GABA(A) receptors and alcoholism (alcohol dependence) was analyzed in the multiplex alcoholic pedigrees collected by the Collaborative Study on the Genetics of Alcoholism (COGA) using family-based association tests. We found consistent, although weak, linkage disequilibrium between GABRB1 (located on chromosome 4) and alcoholism (P < 0.03). Genes encoding GABRA1 and GABRA6, on chromosome 5, did not provide evidence for association with alcoholism. GABRA5 and GABRB3, on chromosome 15, were reported to be expressed uniparentally from the paternal chromosome. Analyses of paternal transmission of alleles of GABRA5 provided evidence for association with alcoholism, particularly in the Caucasian population and with the stricter ICD-10 definition of alcoholism (P < 0.004). Evidence of association was also observed during paternal transmission with GABRB3 in the Caucasian population (P < 0.007). Maternal transmissions provided no evidence for association. These data are consistent with an association between the expressed alleles in the GABA(A)-gene cluster on chromosome 15 and alcoholism that is modulated by genetic imprinting.

Alcoholism↗
PubMed2003

Level of response to alcohol measured on the self-rating of the effects of alcohol questionnaire in a group of 40-year-old women.

A low level of response (LR) to alcohol (i.e., the need for higher amounts to have an effect) is a genetically influenced characteristic that is both found in populations at high risk for future alcoholism and that predicts alcohol-related life problems in the future. A simple paper-and-pencil test that asks subjects to estimate the number of drinks required to produce each of four effects at different times in their lives, the Self-Rating of the Effects of Alcohol (SRE) questionnaire, was developed to facilitate studies of LR. However, data to date on this indirect measure of LR have focused primarily on young male populations. The current study reports SRE values from 121 middle class, middle-aged women who were selected because they were married to men who participated in a longitudinal study of sons of alcoholics and controls. As predicted, the SRE measure of LR, which records the perceived responses of alcohol early in the drinking career (FIRST 5), correlated significantly with recent drinks per drinking day (0.18, p < 0.05), a diagnosis of an alcohol use disorder (0.33, p < 0.001), and with a family history of alcohol dependence (0.20, p < 0.05). The LR value from the SRE reflecting the perceived number of drinks required for effects in the most recent 3 months correlated more closely with both quantity and frequency of drinking (0.36 and higher, p < 0.001), and related to recent nicotine use (0.23, p < 0.05). These data indicate the potential usefulness of the SRE as a measure of LR as a risk factor for alcoholism in relatively highly functioning middle-aged women.

Adult↗
PubMed2003

Genetics of alcoholism using intermediate phenotypes.

This article represents the proceedings of a symposium at the 2002 meeting of the Research Society on Alcoholism in San Francisco, CA. It was organized by Mary-Anne Enoch and David Goldman and chaired by David Goldman. The presentations were (1) Two functional polymorphisms and their intermediate phenotypes in complex behaviors: COMT/executive cognition and anxiety and HTT/anxiety, by David Goldman; (2) Role of the EEG in determining genetic risk for alcoholism and anxiety disorders, by Mary-Anne Enoch; (3) The response to alcohol as an intermediate phenotype for alcoholism, by Marc A. Schuckit; and (4) Pharmacogenomic approaches to alcoholism treatment: toward a hypothesis, by Bankole A. Johnson.

Alcohol Drinking↗
PubMed2003

The validity of DSM-IV alcohol dependence: what do we know and what do we need to know?

This article presents the proceedings of a symposium at the 2002 RSA Meeting in San Francisco, California. Deborah S. Hasin organized the symposium and co-chaired it with Marc Schuckit. The purpose of the symposium was to provide an overview of what is known about the validity of DSM-IV and ICD-10 alcohol dependence and abuse, with a focus on work done since 1994. Presentations included: (1) Validity of DSM-III-R alcohol dependence in adolescents, by Christopher S. Martin; (2) Reliability and validity of DSM and ICD formulations of alcohol use disorders: findings from epidemiology, by Bridget F. Grant; (3) Validity and reliability of the alcohol-dependence phenotype in the context of genetic studies, by Kathleen K. Bucholz; and (4) DSM-IV and beyond: uniting the clinical utility of categories with the precision of dimensions, by John E. Helzer. The findings supported the validity of DSM-IV alcohol dependence across numerous study designs and samples, suggested some value in a dimensional dependence measure, and raised questions about the validity of the diagnosis of alcohol abuse as currently defined. Marc Schuckit, as discussant for the symposium, placed the issues in perspective for the upcoming DSM-V.

Alcoholism↗
PubMed2003

Ethnicity and psychiatric comorbidity among alcohol-dependent persons who receive inpatient treatment: African Americans, Alaska natives, Caucasians, and Hispanics.

This study examined ethnic and gender differences of psychiatric comorbidity among alcohol dependent men and women from four ethnic groups: Alaska Native, Caucasians, African Americans, and Hispanics. The data were obtained through individual standardized interview; DSM-III-R diagnoses were obtained via a computer algorithm. The subjects included 1177 Caucasians, 361 African Americans, 93 Hispanics and 486 Alaska Natives. Significant ethnic differences were found in relation to age of onset of alcohol and multiple substance dependence and psychiatric comorbidity. Ethnic differences were also noted with regard to the health care utilization.

Adult↗
PubMed2003

Predictors and correlates of suicide attempts over 5 years in 1,237 alcohol-dependent men and women.

OBJECTIVE: In previous studies, factors related to a history of suicide attempts in persons with alcohol dependence have included sociodemographic variables, a more severe course of alcoholism, additional substance use disorders, and psychiatric comorbidity. This 5-year prospective study evaluated attributes associated with suicide attempts in a group of treatment-seeking persons with alcohol dependence. Psychiatric comorbidity was examined in terms of a distinction between substance-induced and independent psychiatric disorders. METHOD: Semistructured interviews were conducted with 1,237 alcohol-dependent subjects from the Collaborative Study on the Genetics of Alcoholism both at an initial evaluation and at a 5-year follow-up. Clinically relevant information was gathered at baseline, and suicidal behavior, aspects of alcohol dependence, and drug use were evaluated at the follow-up interview. RESULTS: Alcohol-dependent subjects (N=56) with suicide attempts during the follow-up period were more likely than subjects with no suicide attempts (N=1,181) to have made prior attempts. Other factors related to future suicide attempts in univariate analyses included younger age, being separated or divorced, other drug dependence, substance-induced psychiatric disorders, and indicators of a more severe course of alcoholism. Gender did not predict future attempts. CONCLUSIONS: 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.

Adult↗
PubMed2002

Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus.

Human brain oscillations represent important features of information processing and are highly heritable. A common feature of beta oscillations (13-28 Hz) is the critical involvement of networks of inhibitory interneurons as pacemakers, gated by gamma-aminobutyric acid type A (GABA(A)) action. Advances in molecular and statistical genetics permit examination of quantitative traits such as the beta frequency of the human electroencephalogram in conjunction with DNA markers. We report a significant linkage and linkage disequilibrium between beta frequency and a set of GABA(A) receptor genes. Uncovering the genes influencing brain oscillations provides a better understanding of the neural function involved in information processing.

Adolescent↗