Biomedical subjects

Marc A Schuckit

Publications and source records attributed to Marc A Schuckit.

At least 19 recordsLinked to original sources

PubMed2006

Delta and theta oscillations as risk markers in adolescent offspring of alcoholics.

BACKGROUND: Visual P300 is consistently lower in alcohol-dependent individuals, their offspring and subjects at risk. Delta and theta event-related oscillations (ERO) are the major contributors to the P300 signal. The total and evoked power in delta and theta bands in the 300 to 700 ms post-stimulus window (corresponding to the zone of P300 maxima) was compared between adolescent offspring of alcoholics (high-risk) and age-matched normal controls (low-risk), to assess the utility of the risk markers. METHODS: EEG was recorded during the performance of a visual oddball task. The S-transform algorithm decomposed the EEG signals into different frequency bands and the group differences in total and evoked power in the oscillatory responses during the P300 time window (300 to 700 ms) were analyzed using a multivariate design. Similar analysis was performed on P300 peak amplitude for the target. RESULTS: The high-risk group showed significantly lower parietal post-stimulus evoked and total power in the delta band for targets. A decrease in total power was seen centrally and parietally in the theta band. The P300 peak amplitude in the parietal electrodes was also significantly lower in the high-risk group. CONCLUSIONS: The decreased total theta power and total and evoked delta power for visual targets in high risk individuals may serve as an endophenotypic marker in the development of alcoholism and other disinhibitory disorders. The differences seen between the offspring of alcoholics and controls may have a cholinergic basis. The ERO measures appear to be more robust than the P300 amplitude in differentiating the groups.

Adolescent↗

PubMed2006

Evoked gamma band response in male adolescent subjects at high risk for alcoholism during a visual oddball task.

This study investigates early evoked gamma band activity in male adolescent subjects at high risk for alcoholism (HR; n=68) and normal controls (LR; n=27) during a visual oddball task. A time-frequency representation method was applied to EEG data in order to obtain stimulus related early evoked (phase-locked) gamma band activity (29-45 Hz) and was analyzed within a 0-150 ms time window range. Significant reduction of the early evoked gamma band response in the frontal and parietal regions during target stimulus processing was observed in HR subjects compared to LR subjects. Additionally, the HR group showed less differentiation between target and non-target stimuli in both frontal and parietal regions compared to the LR group, indicating difficulty in early stimulus processing, probably due to a dysfunctional frontoparietal attentional network. The results indicate that the deficient early evoked gamma band response may precede the development of alcoholism and could be a potential endophenotypic marker of alcoholism risk.

Adolescent↗

PubMed2006

Low level of response to alcohol as associated with serotonin transporter genotype and high alcohol intake in adolescents.

BACKGROUND: A low level of response to alcohol has been associated with both the genetic constitution of the regulatory region (SLC6A4) of the human serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) and with future alcohol intake and an increased risk for alcoholism. To date, all studies of relevant polymorphisms have been carried out in populations in the United States. METHODS: Data were extracted from a subset (n = 243) of a cohort of children who have been observed since birth through evaluation of the family history of alcoholism and psychosocial risk influences. At age 16 years, the response to alcohol was assessed with the Self-Rating of the Effects of Alcohol (SRE) questionnaire, and the average amount of alcohol intake per month was assessed during the prior 6 months. Additional variables that were measured included the 5-HTT genotype, externalizing behavior, and sociodemographic variables, such as gender and age. RESULTS: The level of response to alcohol was significantly lower among carriers of two long alleles of the 5-HTT regulatory region compared with carriers of one or two short alleles (Mann-Whitney U = 5225.0, p = .005). In a multiple regression analysis, the level of response to alcohol and externalizing behavior but not psychosocial factors significantly predicted the average amount of alcohol intake per month. CONCLUSIONS: This study demonstrates that, independent of the assessed psychosocial variables, the 5-HTT genotype correlated with the level of response to alcohol and predicted alcohol intake among 16-year-old adolescents.

Adolescent↗

PubMed2006

Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample.

Results from twin studies suggest that overlapping genetic factors influence alcohol dependence and illicit drug dependence. Using data from the Collaborative Study on the Genetics of Alcoholism (COGA), we examined the association between 69 SNPs in the GABAA receptor gene cluster on chromosome 4 and marijuana and illicit drug dependence, individually, and as co-occurring phenotypes with alcohol dependence. Results suggested association between marijuana dependence and illicit drug dependence with SNPs in the GABRA2 gene. Interestingly, the evidence for association previously observed with alcohol dependence came only from individuals with comorbid illicit drug dependence. There was no association with other genes in the GABAA cluster on chromosome 4 with illicit drug dependence.

Alcoholism↗

PubMed2006

A cholinergic receptor gene (CHRM2) affects event-related oscillations.

We report genetic linkage and association findings which implicate the gene encoding the muscarinic acetylcholine receptor M2 (CHRM2) in the modulation of a scalp-recorded electrophysiological phenotype. The P3 (P300) response was evoked using a three-stimulus visual oddball paradigm and a phenotype that relates to the energy in the theta band (4-5 Hz) was analyzed. Studies have shown that similar electrophysiological measures represent cognitive correlates of attention, working memory, and response selection; a role has been suggested for the ascending cholinergic pathway in the same functions. The results of our genetic association tests, combined with knowledge regarding the presence of presynaptic cholinergic M2 autoreceptors in the basal forebrain, indicate that the cognitive processes required by the experiment may in part be mediated by inhibitory neural networks. These findings underscore the utility of electrophysiology and neurogenetics in the understanding of cognitive function and the study of brain-related disorders.

Chromosome Mapping↗

PubMed2006

The relationship of behavioural undercontrol to alcoholism in higher-functioning adults.

Externalising behaviours, including the personality characteristics of behavioural undercontrol (BU), represent one of several genetically influenced domains that impact on the alcoholism risk. Because genes explain only about 60% of the vulnerability toward alcohol use disorders (AUDs), an optimal understanding of how such behaviours affect the risk requires evaluation of their impact in the context of additional influences. Few studies have addressed this question regarding BU among relatively well-functioning adults. This paper presents results from testing a BU-based mediational model of risk in men from the San Diego Prospective Study. Structured research instruments were used with 430 adult Caucasian males to evaluate the performance of BU in predicting AUDs at the 15-year follow-up using Pearson product - moment correlations among domains and an AMOS-based structural equation model (SEM). While both the family history of AUDs (FHalc) and BU predicted alcohol-related outcome, BU by itself did not mediate the relationship of the FH to alcohol disorders. The impact of BU on alcohol problems was mediated by alcohol expectancies, peer drinking and by coping. The SEM explained 42% of the variance for AUDs. The current results indicate that BU contributed to the risk for alcohol-related problems, even among more highly functional subjects and after excluding the impact of the antisocial personality disorder, but by itself did not mediate the relationship of FH to outcome in these subjects.

Adaptation, Psychological↗

PubMed2006

Comorbidity between substance use disorders and psychiatric conditions.

AIM: To review information relevant to the question of whether substance-induced mental disorders exist and their implications. DESIGN AND METHOD: This paper utilized a systematic review of manuscripts published in the English language since approximately 1970 dealing with comorbid psychiatric and substance use disorders. FINDINGS: The results of any specific study depended on the definitions of comorbidity, the methods of operationalizing diagnostic criteria, the interview and protocol invoked several additional methodological issues. The results generally support the conclusion that substance use mental disorders exist, especially regarding stimulant or cannabinoid-induced psychoses, substance-induced mood disorders, as well as substance-induced anxiety conditions. CONCLUSIONS: The material reviewed indicates that induced disorders are prevalent enough to contribute significantly to rates of comorbidity between substance use disorders and psychiatric conditions, and that their recognition has important treatment implications. The current literature review underscores the heterogeneous nature of comorbidity.

Affective Disorders, Psychotic↗

PubMed2006

The empirical basis of substance use disorders diagnosis: research recommendations for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V).

AIMS: This paper presents the recommendations, developed from a 3-year consultation process, for a program of research to underpin the development of diagnostic concepts and criteria in the Substance Use Disorders section of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and potentially the relevant section of the next revision of the International Classification of Diseases (ICD). METHODS: A preliminary list of research topics was developed at the DSM-V Launch Conference in 2004. This led to the presentation of articles on these topics at a specific Substance Use Disorders Conference in February 2005, at the end of which a preliminary list of research questions was developed. This was further refined through an iterative process involving conference participants over the following year. RESULTS: Research questions have been placed into four categories: (1) questions that could be addressed immediately through secondary analyses of existing data sets; (2) items likely to require position papers to propose criteria or more focused questions with a view to subsequent analyses of existing data sets; (3) issues that could be proposed for literature reviews, but with a lower probability that these might progress to a data analytic phase; and (4) suggestions or comments that might not require immediate action, but that could be considered by the DSM-V and ICD 11 revision committees as part of their deliberations. CONCLUSIONS: A broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.

Diagnostic and Statistical Manual of Mental Disord↗

PubMed2006

The development of a research agenda for substance use disorders diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V).

AIMS: This paper describes the background to the establishment of the Substance Use Disorders Workgroup, which was charged with developing the research agenda for the development of the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). It summarizes 18 articles that were commissioned to inform that process. METHODS: A preliminary list of research topics, developed at the DSM-V Launch Conference in 2004, led to the identification of subjects that were subject to formal presentations and detailed discussion at the Substance Use Disorders Conference in February 2005. RESULTS: The 18 articles presented in this supplement examine: (1) categorical versus dimensional diagnoses; (2) the neurobiological basis of substance use disorders; (3) social and cultural perspectives; (4) the crosswalk between DSM-IV and the International Classification of Diseases Tenth Revision (ICD-10); (5) comorbidity of substance use disorders and mental health disorders; (6) subtypes of disorders; (7) issues in adolescence; (8) substance-specific criteria; (9) the place of non-substance addictive disorders; and (10) the available research resources. CONCLUSIONS: In the final paper a broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.

Diagnostic and Statistical Manual of Mental Disord↗

PubMed2006

Understanding and treating alcohol dependence.

This article represents the proceedings of a symposium presented at the 158th Annual Meeting of the American Psychiatric Association held in Atlanta, Georgia, on May 24, 2005. The organizer/chairman was Bankole A. Johnson, DSc, MD, PhD. The presentations included the following: (1) Neuropharmacological Basis of Alcohol Dependence, by George F. Koob, PhD; (2) Recent Developments in the Genetics of Alcohol Dependence, by Marc A. Schuckit, MD; (3) New Pharmacological Strategies for Treating Alcohol Dependence, by Barbara J. Mason, PhD; (4) New Medications: The Use of Anticonvulsants, Both Alone and in Combination, with Various Forms of Psychotherapy, by Bankole A. Johnson, DSc, MD, PhD; and (5) Differential Effects of Pharmacological Agents on Craving, by Nassima Ait-Daoud, MD.

Alcoholism↗

PubMed2006

Should DSM-V include dimensional diagnostic criteria for alcohol use disorders?

This program calls attention to the upcoming timetable for the revision of the Diagnostic and Statistical Manual (DSM)-IV and the publication of DSM-V. It is vitally important for Research Society of Alcoholism members to be aware of the current discussions of the important scientific questions related to the next DSM revision and to use the opportunity for input. The title of the symposium highlights 1 key question, i.e., whether the DSM definitions should remain strictly categorical as in the past or whether a dimensional component should be included in this revision. Two substantive and 1 conceptual paper are included in this portion of the symposium. The fourth and final presentation detailing the revision timetable and the opportunities for input is by Dr. Darrel Regier. Dr. Regier is the director of American Psychiatric Institute for Research and Education the research and education branch of the American Psychiatric Association and the organization within the APA that will oversee the DSM revision. The discussion is by Marc Schuckit, who was chair of the Substance Use disorders (SUD) Committee for DSM-IV and cochair of the international group of experts reviewing the SUD definitions for DSM-V.

Alcohol Drinking↗

PubMed2006

Searching for the full picture: structural equation modeling in alcohol research.

This article summarizes the proceedings of a symposium presented at the 2005 Research Society on Alcoholism meeting in Santa Barbara, California. This symposium begins with a description by Michael Windle of structural equation modeling (SEM), including the assets and liabilities of this approach. Next, Marc Schuckit and Tom Smith demonstrate the application of an SEM approach to understanding the impact of a low level of response to alcohol, using data from both adolescent and adult populations. Victor Hesselbrock and colleagues next review the results when an SEM approach is used in the longitudinal study of externalizing behaviors. This is followed by a description of the application of SEM to an affect-related model as discussed by John Kramer and Kathleen Bucholz. Finally, Kenneth Sher offers thoughts on how to place these findings into perspective.

Adaptation, Psychological↗

PubMed2006

Alcohol attenuates load-related activation during a working memory task: relation to level of response to alcohol.

BACKGROUND: A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. METHOD: Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level-dependent activation to an event-related visual working memory test was examined. RESULTS: The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load-dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. CONCLUSION: Low-level responders relative to high-level responders exhibited an increased working memory load-dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol.

Adult↗

PubMed2006

Associations of variations in alcohol dehydrogenase genes with the level of response to alcohol in non-Asians.

BACKGROUND: Risk and protective factors for alcohol use disorders (AUDs) are complex and reflect both environmental and genetic factors. Genetic components account for about 50% of the variation and influence several phenotypes, including the level of response (LR) to alcohol as well as alcohol-metabolizing enzyme polymorphisms. Variations in the ADH1B and ADH1C genes may influence the LR to alcohol by increasing levels of acetaldehyde during alcohol metabolism, although most data on this question come from Asian populations. METHODS: This study evaluated associations of ADH1B and ADH1C genotypes in a non-Asian sample. Participants (N = 117, 69.2% female) were 18- to 29-year-old men and women, primarily Caucasian (70.1%) and black (26.5%), recruited in San Diego, California. The Semi-Structured Assessment for the Genetics of Alcoholism Interview was used to assess demographic, substance use, and psychiatric history information, and the Family History Assessment Module was used to determine first-degree family history of alcohol dependence. An alcohol challenge paradigm was used to gather data on the LR to alcohol over 210 minutes. RESULTS: Participants with the ADH1B*1/*2 genotype had a higher LR to alcohol early in the alcohol challenge (i.e., 30, 60, and 90 minutes after drinking) as measured by both alcohol-related changes in subjective feelings of intoxication and body sway, even when controlling for sex and Russian/Eastern European ancestry. A similar trend was seen for ADH1C*1/*1 genotype, although the results were not significant. CONCLUSIONS: These findings suggest that studies searching for genes relating to the LR to alcohol as a vulnerability factor for AUDs should consider controlling for ADH1B genotype, as the ADH1B*2 allele could obscure the impact of other genetic polymorphisms.

Adolescent↗

PubMed2006

Comparison of psychiatric diagnoses from interview reports with those from best-estimate procedures.

OBJECTIVE: The aim of this study was to compare psychiatric diagnoses based on interview information with those based on best-estimate procedures, to evaluate information used in such procedures, and to use 5-year follow-up data to determine whether the best-estimate diagnosis is an improvement over the interview-based diagnosis. METHOD: Psychiatric diagnoses were based on interview reports from 373 probands and 2615 relatives participating in a high-risk family study of alcoholism. The diagnosis also included clinician ratings in a best-estimate procedure of this study. RESULTS: For most diagnoses, both sensitivity and specificity, using the best-estimate diagnosis (BED) as the gold standard, were excellent, in both relatives and probands. Substance abuse was an exception, with very low sensitivity, although specificity rates were excellent. For nonsubstance diagnoses, specificity was high, but sensitivity ranged from 59% to 84% across relatives and probands. In general, BED procedures led to higher prevalence estimates than those from the interview only. In the BED process, family history data were especially useful for conduct and antisocial personality disorders. Follow-up interview data supported the fact that BED procedures led to both enhancements of, as well as errors in, diagnosis. CONCLUSIONS: Our data attest to the utility of family history information, particularly for antisocial personality disorder and conduct disorder, and indicate that, for the phenotype of substance-dependence disorder, an interview-based diagnosis alone is adequate in classifying individuals with a minimum of error. These results should be reassuring for research studies in which costs and resources required for best-estimate procedures are not affordable.

Adult↗

PubMed2006

Marital status, alcohol dependence, and GABRA2: evidence for gene-environment correlation and interaction.

OBJECTIVE: The gene GABRA2 has been associated with the risk for alcohol dependence in independent samples. This article explores how this genetic risk factor interacts with marital status, another factor previously shown to be associated with the risk for alcohol dependence. METHOD: Data from more than 1,900 male and female subjects from the Collaborative Study of the Genetics of Alcoholism (COGA) sample were analyzed. Subjects were recruited based on membership in a family with multiple individuals with alcoholism. A series of analyses was performed to evaluate the relationship between the following: (1) GABRA2 and alcohol dependence, (2) marital status and alcohol dependence, (3) GABRA2 and marital status, and (4) interactions between GABRA2 and marital status on the development of alcohol dependence in the high-risk COGA sample. Additional analyses were carried out in a sample of approximately 900 individuals from control families to test the generalizability of results. RESULTS: Both GABRA2 and marital status contributed independently to the development of alcohol dependence in the COGA sample. The high-risk genotype at GABRA2 was also related to a decreased likelihood of marrying and an increased likelihood of divorce, which appeared to be mediated in part by personality characteristics. There was also differential risk associated with the GABRA2 genotype according to marital status. CONCLUSIONS: These analyses provide evidence of both gene-environment correlation and gene-environment interaction associated with GABRA2, marital status, and alcohol dependence. They illustrate the complex pathways by which genotype and environmental risk factors act and interact to influence alcohol dependence and challenge traditional conceptualizations of "environmental" risk factors.

Adolescent↗

PubMed2006

An evaluation of the level of response to alcohol, externalizing symptoms, and depressive symptoms as predictors of alcoholism.

OBJECTIVE: The development of alcohol-use disorders (AUDs) reflects a complex relationship between genetic influences and environmental/cultural forces. Some genes operate through intermediate phenotypes, including a low level of response (LR) to alcohol, externalizing symptoms (EXT), and internalizing characteristics such as depressive syndromes (DEP). This article evaluates the impact of these three intermediate phenotypes and additional domains in a structural equation model (SEM). METHOD: Data were available from baseline at approximately age 20 for LR, as well as from additional domains at the 10- and 15-year follow-up periods for 393 men from the San Diego Prospective Study. Correlational analyses and an AMOS-based SEM were used to evaluate the development of alcohol problems, including AUDs, with the hypothetical model based on results from prior studies evaluating each key intermediate phenotype separately. RESULTS: The SEM explained 51% of the variance of the 15-year outcome, and had good fit characteristics. The family history ofAUDs (FHalc) was linked, directly or indirectly, to all three key domains. The combination of LR and EXT mediated the relationship between FHalc and 15-year alcohol outcomes, with a trend (p = .07) for LR to mediate between FHalc and the 10-year outcome. DEP, by itself, did not mediate FHalc to alcoholism. The LR predicted the 15-year outcome both through alcohol problems at 10 years and via drinking to cope (COPE), with each of these domains functioning as mediators. The relationship of EXT to outcome was mediated by alcohol expectations (EXPECT) and by COPE. DEP added to the model in the context of an FH of independent depressions, stress, and lower social supports, subsequently affecting COPE. CONCLUSIONS: The results indicate that the development of AUDs reflects several genetically influenced endophenotypes in the context of multiple additional domains. Both EXPECT and COPE represented important pathways through which the phenotypes influenced the AUD risk.

Adaptation, Psychological↗

PubMed2006

An evaluation of the performance of the self-rating of the effects of alcohol questionnaire in 12- and 35-year-old subjects.

OBJECTIVE: A low level of response (LR) to alcohol was originally established through evidence of less alcohol-related change in several parameters at a given blood alcohol level. This is a genetically influenced phenotype associated with an increased risk for alcoholism. When measured by a retrospective questionnaire (the Self-Rating of the Effects of Alcohol [SRE] scale), a lower LR (here indicated by a report that more drinks were historically needed for various effects) correlates with a family history of alcoholism and numerous alcohol use-related variables. The current analyses address the questions of how higher SRE scores (as indicators of a low LR) relate to alcohol use and problems across different age groups and when considered in the context of demography (e.g., age, gender, and weight), as well as the number of items endorsed on the questionnaire. METHOD: SRE data (scores and numbers of items endorsed), demography, and alcohol-related variables (quantity, frequency, and problems) were evaluated in two populations. The first population included 334 12-year-old children from the Avon Longitudinal Study of Parents and Children, and the second included more than 400 35-year-old men from the San Diego Prospective Study. In each group, Pearson correlations were established among all variables, and items that were significantly linked to alcohol-related outcomes were entered into regression analyses as predictors of these outcomes. RESULTS: In both samples, SRE scores correlated with all alcohol-related outcomes, with the highest values for the maximum quantity of alcohol consumed. Relationships between the SRE score and alcohol-related variables remained robust in both populations when entered into regression analyses incorporating demography and the number of SRE items answered by subjects. CONCLUSIONS: The SRE score appears to perform relatively similarly across the two populations regarding relationships with alcohol quantity, frequency, and problems. The most consistent results were observed for the maximum quantity of alcohol consumed.

Adolescent↗