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M Schuckit

Publications and source records attributed to M Schuckit.

At least 19 recordsLinked to original sources
PubMed2006

Association of the kappa-opioid system with alcohol dependence.

Opioid receptors and their endogenous peptide ligands play important roles in the reward and reinforcement of drugs such as heroin, cocaine, and alcohol. The binding of dynorphins to the kappa-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the kappa-opioid receptor, and PDYN, which encodes its ligand prodynorphin, in a group of 1860 European American individuals from 219 multiplex alcohol dependent families. Family-based analyses demonstrated associations between alcohol dependence and multiple SNPs in the promoter and 3' end of PDYN, and in intron 2 of OPRK1. Haplotype analyses further supported the association of PDYN. Thus, variations in the genes encoding both the kappa-opioid receptor and its ligand, OPRK1 and PDYN, are associated with the risk for alcohol dependence; this makes biological sense as variations in either should affect signaling through the kappa-opioid system.

Alcoholism↗
PubMed2001

Evidence for a locus on chromosome 1 that influences vulnerability to alcoholism and affective disorder.

OBJECTIVE: Depression (major depression or depressive syndrome) is more prevalent in alcoholic than in nonalcoholic subjects in families with multiple members with alcoholism studied as part of the Collaborative Study on the Genetics of Alcoholism (National Institute on Alcohol Abuse and Alcoholism). First-degree relatives of probands with comorbid alcoholism and depression have a higher prevalence of both disorders than relatives of probands with alcoholism alone, and both groups have a higher prevalence than the relatives of comparison subjects selected without regard to psychopathology. Data from the collaborative study were used to test three phenotypes (comorbid alcoholism and depression, alcoholism or depression, and depression) for genetic linkage. METHOD: Genome-wide sibling-pair linkage analyses were performed with the phenotypes comorbid alcoholism and depression, alcoholism or depression, and depression (major depression or depressive syndrome). Analyses were performed in two data sets (initial and replication data sets) from subject groups ascertained with identical criteria, as well as in the combined data set. RESULTS: Peak lod scores on chromosome 1 (near 120 centimorgan) for the alcoholism or depression phenotype were 5.12, 1.52, and 4.66 in the initial, replication, and combined data sets, respectively. The corresponding lod scores on chromosome 2 were 2.79, 0.20, and 3.26; on chromosome 6, they were 3.39, 0.00, and 0.92; and on chromosome 16, they were 3.13, 0.00, and 2.06. Lod scores on chromosome 2 for the comorbid alcoholism and depression phenotype in the three data sets were 0.00, 4.12, and 2.16, respectively. CONCLUSIONS: The results suggest that a gene or genes on chromosome 1 may predispose some individuals to alcoholism and others to depression (which may be alcohol induced). Loci on other chromosomes may also be of interest.

Adult↗
PubMed2000

Alcoholism susceptibility loci: confirmation studies in a replicate sample and further mapping.

BACKGROUND: There is substantial evidence for a significant genetic component to the risk for alcoholism. A previous study reported linkage to chromosomes 1, 2, and 7 in a large data set that consisted of 105 families, each with at least three alcoholic members. METHODS: Additional genotyping in the 105 families has been completed in the chromosomal regions identified in the initial analyses, and a replication sample of 157 alcoholic families ascertained under identical criteria has been genotyped. Two hierarchical definitions of alcoholism were employed in the linkage analyses: (1) Individuals who met both Feighner and DSM-III-R criteria for alcohol dependence represented a broad definition of disease; and (2) individuals who met ICD-10 criteria for alcoholism were considered affected under a more severe definition of disease. RESULTS: Genetic analyses of affected sibling pairs supported linkage to chromosome 1 (LOD = 1.6) in the replication data set as well as in a combined analysis of the two samples (LOD = 2.6). Evidence of linkage to chromosome 7 increased in the combined data (LOD = 2.9). The LOD score on chromosome 2 in the initial data set increased after genotyping of additional markers; however, combined analyses of the two data sets resulted in overall lower LOD scores (LOD = 1.8) on chromosome 2. A new finding of linkage to chromosome 3 was identified in the replication data set (LOD = 3.4). CONCLUSIONS: Analyses of a second large sample of alcoholic families provided further evidence of genetic susceptibility loci on chromosomes 1 and 7. Genetic analyses also have identified susceptibility loci on chromosomes 2 and 3 that may act only in one of the two data sets.

Alcoholism↗
PubMed1999

Description of the Genetic Analysis Workshop 11 Collaborative Study on the Genetics of Alcoholism.

Problem 1 of Genetic Analysis Workshop 11 consists of data from a family study of the genetics of alcoholism and related traits contributed by the six centers making up the National Institute for Alcohol Abuse and Alcoholism sponsored by the Collaborative Study on the Genetics of Alcoholism (COGA). The family data included 1,214 members of 105 pedigrees ascertained for having three or more individuals affected with alcoholism. Data available to workshop participants included clinical phenotypes, personality measures, smoking behavior, event-related potentials, platelet monamine oxidase B activity, and a genome scan of 296 markers.

Alcoholism↗
PubMed1999

A validity study of the SSAGA--a comparison with the SCAN.

OBJECTIVE: This study examined the concurrent diagnostic validity of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) across alcohol and drug dependencies, major depression, anxiety disorders and ASPD. The Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was selected as the comparison instrument because it arises from a different tradition and uses a different format for its administration. The SCAN has been shown to be valid and applicable cross-culturally. METHOD: Subjects included 38 men and 42 women volunteers from another study and from an outpatient psychiatry clinic. Selected sections of both the SSAGA and the SCAN interviews were administered to all subjects, approximately 1 week apart, in a randomized order. Because the SCAN does not assess Antisocial Personality Disorder (ASPD), the ASPD section of the Structured Clinical Interview for DSM-III-R (SCID) was substituted for this comparison. RESULTS: The Kappa statistic was used to measure concordance between the two instruments. Kappa for alcohol dependence was in the acceptable range (0.63). Kappas were lower for sedative dependence (0.48) and for cannabis dependence (0.53), but higher for cocaine and stimulant dependence (0.85) and for opioid dependence (0.73). Kappa for major depression and the ASPD diagnoses were high (0.71 and 0.70), but slightly lower agreement was found for panic disorder (0.62). Kappa for social phobia was 0.47. CONCLUSION: These data, combined with results from two previous studies which examined reliability, indicate that the SSAGA is a highly reliable and valid instrument for use in studies of a variety of psychiatric disorders, including alcohol and drug dependence.

Adolescent↗
PubMed1998

Anxiety proneness linked to epistatic loci in genome scan of human personality traits.

A genome-wide scan between normal human personality traits and a set of genetic markers at an average interval of 13 centimorgans was carried out in 758 pairs of siblings in 177 nuclear families of alcoholics. Personality traits were measured by the Tridimensional Personality Questionnaire. We detected significant linkage between the trait Harm Avoidance, a measure of anxiety proneness, and a locus on chromosome 8p21-23 that explained 38% of the trait variance. There was significant evidence of epistasis between the locus on 8p and others on chromosomes 18p, 20p, and 21q. These oligogenic interactions explained most of the variance in Harm Avoidance. There was suggestive evidence of epistasis in other personality traits. These results confirm the important influence of epistasis on human personality suggested by twin and adoption studies.

Anxiety↗
PubMed1998

Increased REM sleep density at admission predicts relapse by three months in primary alcoholics with a lifetime diagnosis of secondary depression.

BACKGROUND: Having previously reported that 3-month relapse was associated with increased admission REM pressure in nondepressed primary alcoholics, we hypothesized that baseline polysomnography would predict outcome in primary alcoholics with a lifetime diagnosis of secondary depression. METHODS: Twenty-one primary alcoholics with secondary depression received polysomnography and the Hamilton Depression Rating Scale during the first and fourth weeks of a 1-month inpatient alcohol treatment program. Exclusion criteria included serious illness, current major alcohol withdrawal symptoms, other Axis I diagnoses, sleep apnea, nocturnal myoclonus, and psychoactive substances within 14 days of polysomnography. Relapse was defined as drinking any alcohol between hospital discharge and 3-month follow-up. RESULTS: Relapsers' total sleep time was reduced, and REM density (reflecting REM sleep ocular activity) was increased significantly throughout admission compared with abstainers. Sleep continuity and Hamilton scores improved by discharge in sober and relapsing alcoholics. Factors derived from admission REM latency, REM percent, and REM density predicted sobriety vs. relapse within 3 months after hospital discharge in 76% of patients. Admission REM density was greater, and total sleep time was less in relapsers than in patients sober at 3 months. CONCLUSIONS: Results suggest that increased REM density and decreased total sleep time at about 2-4 weeks of abstinence predict relapse by 3 months in depressed alcoholics.

Adult↗
PubMed1998

A family-based analysis of the association of the dopamine D2 receptor (DRD2) with alcoholism.

The possible association of the DRD2 locus, and in particular the Taql-A1 allele, with alcoholism remains controversial, in part because of differences in allele frequencies among populations. To avoid problems associated with differences in allele frequencies in different populations, we tested whether the DRD2 locus is associated with alcohol dependence in a large family-based sample. Neither the transmission/disequilibrium test nor the Affected Family-Based Controls test provide any evidence of linkage or association between the DRD2 locus and alcohol dependence.

Alcoholism↗
PubMed1998

A family-based analysis of whether the functional promoter alleles of the serotonin transporter gene HTT affect the risk for alcohol dependence.

A population association between a regulatory variation in the promoter of the serotonin transporter gene (HTT) and severe alcohol dependence was recently reported. We analyzed this potential association in a large number of systematically ascertained families in the United States; these families had at least three first-degree relatives who were alcohol-dependent. Analyses focused on individuals defined as alcohol-dependent by criteria from ICD-10 and on subsets of these individuals reporting withdrawal-related symptoms. Application of the transmission disequilibrium test did not provide support for either linkage or association between this functional polymorphism and alcohol dependence; there was no significant bias in the transmission of either allele to the alcohol-dependent offspring. We also report that African Americans differ from Caucasians in allele frequencies for this polymorphism.

Adult↗
PubMed1998

Linkage of an alcoholism-related severity phenotype to chromosome 16.

There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four-class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes 3 and 4 had higher symptom endorsement probabilities than classes 1 and 2 for items reflecting severe alcohol dependence, and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met the Collaborative Study of the Genetics of Alcoholism, and >99% met ICD-10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15 cM interval.

Adult↗
PubMed1994

Increased pressure for rapid eye movement sleep at time of hospital admission predicts relapse in nondepressed patients with primary alcoholism at 3-month follow-up.

OBJECTIVE: To determine whether polygraphic sleep recordings, obtained at the time of admission to an inpatient alcohol treatment program, predict abstinence and relapse 3 months following hospital discharge in nondepressed patients with primary alcoholism. DESIGN: Two independent, consecutive cohorts of patients (group 1, n = 28; group 2, n = 17) underwent all-night polygraphic sleep recordings and other clinical evaluations during the first and fourth weeks of a 1-month inpatient treatment program within a Veteran Affairs Medical Center. They were reevaluated 3 months following discharge to the community. None were treated with disulfiram or other medications during or after hospitalization. PATIENTS: All subjects were male veterans with primary alcoholism and without significant preexisting, secondary, or comorbid diagnoses such as major medical problems, depression, antisocial personality, or drug addiction. OUTCOME MEASURES: Relapse was defined as any alcohol consumption between discharge from the hospital and 3-month follow-up. RESULTS: Ten (36%) of 28 patients in group 1 were Relapsers at 3-month follow-up. Relapsers in group 1 showed significantly shorter Rapid Eye Movement (REM) latency, increased Rapid Eye Movement percent (REM%), and increased REM Density during their admission sleep studies compared with Abstainers. To replicate these observations, group 2 was then studied as a validation sample. Six (35%) of 17 patients relapsed. As in group 1, Relapsers had significantly shorter REM latency and increased REM% compared with Abstainers; REM Density was not significantly different in the Relapsers as compared with Abstainers in group 2. Using a principal components analysis based on these three REM sleep measures to determine "REM pressure," three separate discriminant function analyses (DFAs) were calculated: one for each group and one for all patients (n = 45) together. The DFA from group 1 correctly classified 22 (78.6%) of the 28 patients in group 1 and 13 (76.5%) of the 17 patients in group 2 as Relapsers or Abstainers. The DFA from group 2 correctly classified 13 (76.5%) of the 17 patients in group 2 and 23 (82.1%) of the 28 patients in group 1. The DFA formed from both groups together correctly classified 36 (80%) of the 45 patients. When the REM sleep measures at hospital admission and discharge were compared, no statistically significant effect of time was observed. Abstinence and relapse were not consistently related to other clinical measures at the time of hospital admission such as age, duration and severity of alcoholism, marital status, employment, hepatic enzyme levels, cognitive performance, or depression ratings. CONCLUSION: Short REM latency, increased REM%, and, possibly, increased REM Density at the time of admission to a 1-month inpatient alcohol treatment program predict relapse in nondepressed patients with primary alcoholism by 3 months following hospital discharge.

Alcohol Drinking↗
PubMed1993

A comparison of sleep EEGs in patients with primary major depression and major depression secondary to alcoholism.

Polygraphic sleep recordings were compared between patients with primary major depression (MDD), patients with primary alcoholism and secondary MDD, and normals. Patients differed significantly from normals on the following measures: both patient groups showed short REM latency, and REM latency corrected, along with prolonged sleep latency. Secondary depressives differed from controls on several other measures: sleep onset time, total sleep time, delta sleep, REM percent, stage one sleep, stage three sleep, non-REM sleep, stage three and delta sleep in the first non-REM period. Prior research has shown a decrease in non-REM sleep and total sleep time in alcoholic patients who are not currently depressed, and short REM latency in patients with MDD. Thus, our findings suggest an additive effect of two disorders known to affect sleep: alcoholism and depression.

Adult↗
PubMed1993

A review of the substance use disorders section of the DSM-IV.

The DSM-IV work groups are the first to be given the opportunity to document carefully all stages of deliberations and make decisions based on carefully constructed and data-based criteria. The 5-year process has encouraged the use of detailed literature reviews and allowed members of the working groups to generate data from both MacArthur analyses and field trials to make the most appropriate decisions possible. The Substance Use Disorders Work Group was faced with a potentially infinite number of questions that could be asked. The guidelines presented at the beginning of this article, especially the focus on areas in which data are already available or might potentially be generated from a field trial, allowed our Work Group to focus on a limited number of questions. With rare exceptions, each of these areas was evaluated by the thorough literature reviews that have formed the chapters that make up this section of the Sourcebook. Our goals are relatively straightforward. It is important that clinicians, researchers, administrators, and those who will work the DSM-IV process have full access to the state of the literature that existed in the late 1980s and early 1990s, and the decision-making process that was used to address the issues that affected the DSM-IV. It is hoped that this article will not only help readers to understand both how and why the DSM-IV Substance Use Disorders Work Group made the relevant decisions, but will also encourage active research to answer more fully the potentially important questions raised in these reviews.

Humans↗
PubMed1992

Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism.

Blum et al (1990) have recently examined a restriction fragment length polymorphism (RFLP) detected by TaqI RFLP to the dopamine D2 receptor gene (DRD2) in deceased alcoholics and nonalcoholics, and reported an association between alcoholism and the A1 allele. Subsequent studies, however, by other investigators have failed to confirm this. We have examined the DRD2 TaqI RFLP in 47 living Caucasian males with severe alcoholism. All alcoholic subjects were thoroughly characterized by a structured interview, and met DSM-III-R criteria for alcohol dependence. Only 9/47 (19%) (1990) of these alcoholics had the AI allele compared to 14/22 (64%) reported by Blum et al. This rate was not significantly different from the rates reported in control populations by Blum et al (1990), CEPH, or Bolos et al (1990), and differed only slightly from those reported by Grandy et al (1990). Alcoholics selected for severe medical complications also displayed a similar rate. Our data do not support an association between alcoholism and the D2 dopamine receptor gene in this population.

Adult↗
PubMed1991

Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging.

Twenty-eight chronic alcoholics and 36 age- and sex-matched non-alcoholic controls were examined with magnetic resonance imaging and brain morphometric analyses. Results confirmed large increases in subarachnoid cerebrospinal fluid (CSF) volume and mild ventricular enlargement in the alcoholics and revealed associated volume reductions of localized cortical and subcortical cerebral structures. Volume losses in the diencephalon, the caudate nucleus, dorsolateral frontal and parietal cortex, and mesial temporal lobe structures were the most prominent. Significant correlations between increments in cortical and ventricular CSF and decrements in the volume of cortical and subcortical grey matter were noted. Although there was little evidence for relationships between performance on neuropsychological tests and volume of grey matter structures, significant correlations between some cognitive measures and subcortical and cortical fluid volumes were found. The parallels between this pattern of affected structures and recent neuropathological findings are discussed.

Adult↗
PubMed1991

Cognitive performance of alcoholics: a longitudinal evaluation of the role of drinking history, depression, liver function, nutrition, and family history.

To assess the role of drinking history, depression, liver function, nutrition, and family history on cognitive performance, 171 detoxified male alcoholics were administered a brief neuropsychological examination at admission and discharge from an inpatient treatment program and at a 3-month follow-up evaluation. Regression analyses showed that at admission, depression and liver function were significant predictors of neuropsychological performance, whereas at discharge 3 to 4 weeks later only age and an estimate of premorbid intelligence were significant predictors. At the 3-month follow-up, estimates of drinking following discharge and severity of depressive symptoms were major significant predictors of neuropsychological performance. Indices of drinking prior to admission to the treatment program, nutrition, and family history for alcoholism did not predict performance on any of the three test occasions. These findings indicate that in addition to the chronic neurotoxic effect of alcohol a number of different medical and psychiatric factors, as well as the acute effects of alcohol, contribute to the cognitive scores of patients at various points in the clinical course.

Adult↗
PubMed1990

EEG sleep studies in "pure" primary alcoholism during subacute withdrawal: relationships to normal controls, age, and other clinical variables.

Electroencephalogram (EEG) sleep recordings were compared in 34 normal controls and 31 inpatients with relatively pure primary alcoholism who had been abstinent for about 17 days. Compared with normal controls, primary alcoholics took longer to fall asleep, slept less, and had poor sleep efficiency. Sleep loss reflected reduced non-rapid eye movement (NREM) sleep, especially stage 2 sleep, stage 4 sleep, and total delta (stage 3 and 4) sleep. Alcoholic patients had higher REM density of the first REM period. Sleep deteriorated with age in both normal controls and patients, with younger alcoholics showing sleep patterns typical of older controls. Among other clinical-demographic variables examined, the shorter the duration of sobriety at the time of the study, the later patients went to bed and fell asleep. The number of drinks per drinking day in the 3 months before admission was directly related to the duration of the first REM period. In addition, the maximum number of withdrawal symptoms the patient had ever experienced was inversely related to the amount of delta sleep. Sleep measures were not correlated with depression rating, liver enzymes, or other measures of alcohol consumption.

Adult↗