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H Begleiter

Publications and source records attributed to H Begleiter.

At least 37 records · Page 2Linked to original sources
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

Structural decomposition of genetic diversity in families with alcoholism.

Using genotypes of 280 marker loci on the 22 autosomes of 105 alcohol-dependent probands, their affected and unaffected sibs, as well as their parents, we iteratively constructed a genetic similarity function that enabled us to quantify the interindividual genetic distances d(x(i), xj) between feature vectors x(i), xj made up by the allelic patterns of individuals i, j with respect to loci l1, l2,...,ln. Based on this similarity function, we investigated the sib-sib similarities that are expected to deviate from "0.5" in affected sib pairs if the region of interest contains markers close to disease-causing genes. The reference value "0.5" was derived from the parents-offspring similarities, because these are independent of the affection status. The question of population admixture was addressed by means of multivariate structural analyses. These analyses led to four "natural" groups whose validity was tested through the father-mother similarities. Additionally, we determined the eigenvectors that optimally represented the genetic variation and found several marker configurations on chromosomes 1, 3, 7, 15, and 17 that reproducibly discriminated (p < or = 0.01) affected probands/sibs from unaffected sibs, while no such differences were found between affected probands and affected sibs.

Alcoholism↗
PubMed1999

Local polynomial estimate of surface Laplacian.

This paper describes a method for estimating the surface Laplacian of brain potentials. The method consists of two steps: local surface approximation by its tangent plane and local polynomial fitting. Compared to previous methods for estimating surface Laplacian, this method has some new features. First, it can estimate the surface Laplacian at any point of the scalp, including the locations of the peripheral electrodes. Secondly, it estimates the brain potential and the surface Laplacian at any point simultaneously. This reduces the risk of error propagation, which occurs when the brain potential is interpolated first and the surface Laplacian is then computed based on the interpolated brain potential. Finally, the method automatically adapts to noisy data by using more or less measurements at neighboring electrodes based on estimated noise level. Simulations suggest that this method is effective. Application to event-related potentials are also presented.

Action Potentials↗
PubMed1999

P300: the similarities and differences in the scalp distribution of visual and auditory modality.

PURPOSE: To examine the topographic relationship of P3(00) between the visual and auditory modalities, especially to examine whether there are any modality-specific hemispheric differences of P3 in normal adults. METHODS: The P3s were recorded from the same 41 normal right-handed males between the ages of 20 and 33 in both a typical auditory oddball task and a visual oddball paradigm with novel stimuli, with an extensive set of 61 scalp electrodes. In addition to the visual comparison and quantitative assessment of current source density (CSD) maps between the two modalities, canonical correlation analyses on the P3 raw amplitudes and examination of interaction effects of modality x location on both raw and normalized P3 data were performed. RESULTS: The canonical correlation between modalities was generally high, especially at the left parietal brain region. There were no significant hemispheric effects in anterior brain but significant left-greater-than-right hemispheric effects in posterior brain regions in both modalities; modality-specific hemispheric effect was observed only at the parietal region. Strong surface current density activities were observed in the midline parietal-occipital area, and left and right boundary areas of temporal and inferior frontal region. CONCLUSIONS: The topographic similarities between P3s recorded in the visual and auditory modality outnumber the differences. Combining data from CSD assessments and profile analysis of P3 topography support the hypothesis of multiple generators of P3 that are differentially active in processing stimuli from different sensory modalities and are not symmetrically distributed between the two hemispheres.

Acoustic Stimulation↗
PubMed1999

Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. II. Alcoholism and event-related potentials.

The availability of robust quantitative biological markers that are correlated with qualitative psychiatric phenotypes can potentially improve the power of linkage methods to detect quantitative-trait loci influencing psychiatric disorders. We apply a variance-component method for joint multipoint linkage analysis of multivariate discrete and continuous traits to the extended pedigree data from the Collaborative Study on the Genetics of Alcoholism, in a bivariate analysis of qualitative alcoholism phenotypes and quantitative event-related potentials. Joint consideration of the DSM-IV diagnosis of alcoholism and the amplitude of the P300 component of the Cz event-related potential significantly increases the evidence for linkage of these traits to a chromosome 4 region near the class I alcohol dehydrogenase locus ADH3. A likelihood-ratio test for complete pleiotropy is significant, suggesting that the same quantitative-trait locus influences both risk of alcoholism and the amplitude of the P300 component.

Alcohol Dehydrogenase↗
PubMed1999

Evaluation of ADHD typology in three contrasting samples: a latent class approach.

OBJECTIVE: To identify subtypes of attention-deficit/hyperactivity disorder (ADHD) and characterize them as either categorical or continuous; to investigate familial resemblance for ADHD among sibling pairs; and to test the robustness of all results by using contrasting data sets. METHOD: Latent class analysis was applied to the ADHD symptom profiles obtained from parents or best informant about their offspring in 3 samples: a population-based set of female adolescent twins (724 monozygotic pairs, 594 dizygotic pairs) and male (N = 425) and female (N = 430) child and adolescent offspring ascertained from high-risk alcoholic families. RESULTS: Latent class analysis revealed 2 categories of clinically significant ADHD which were replicated in all 3 study groups: a subtype with high endorsements of ADHD inattention symptoms and a second combined type with high endorsements of both inattention and hyperactivity-impulsivity items. Both appeared to be continuous across all 3 data groups. The high-risk families contained a class in which members heavily endorsed the ADHD "fidget" item but not other ADHD items. A large proportion of the monozygotic sibs (80%) versus a smaller proportion of dizygotic sibs (52%) were assigned to the same latent class. Among the high-risk children and adolescents, 51% of the female and 41% of the male siblings were concordant for class membership. CONCLUSIONS: The pattern of latent classes suggested that ADHD consists of an inattentive and a combined subtype, within each of which lies a dimensional domain. These analyses further support that genetic factors are significant determinants of latent class membership.

Adolescent↗
PubMed1999

What is inherited in the predisposition toward alcoholism? A proposed model.

BACKGROUND: The etiological factors associated with the predisposition to develop alcohol dependence remain largely unknown. In recent years, neurophysiological anomalies have been identified in young and adult offspring of alcoholic probands. These neuroelectric features have been replicated in several laboratories across many different countries and are observed in male and female alcoholics and some of their relatives and offspring. Moreover, these electrophysiological abnormalities are heritable and predictive of future alcohol abuse or dependence. METHODS: A model is presented which hypothesizes that the genetic predisposition to develop alcoholism involves an initial state of central nervous system (CNS) disinhibition/hyperexcitability. We propose that the event-related brain potential (ERP) anomalies reflect CNS disinhibition. This homeostatic imbalance results in excess levels of CNS excitability which are temporarily alleviated by the ingestion of alcohol. It is hypothesized that this hyperexcitability is heritable, and is critically involved in the predisposition toward alcoholism and the development of dependence. A brief review of the relevant literature is presented. RESULTS: Neurophysiological, neurochemical, and genetic evidence support the proposed model. In addition, strikingly similar observations between animal research and the human condition are identified. Finally, it is asserted that the proposed model is primarily biological in nature, and therefore does not account for the entire clinical variance. CONCLUSION: A putative CNS homeostatic imbalance is noted as a critical state of hyperexcitability. This hyperexcitability represents a parsimonious model of what is inherited in the predisposition to develop alcoholism. It is our hope that this model will have heuristic value, resulting in the elucidation of etiological factors involved in alcohol dependence.

Adult↗
PubMed1999

Visual P3a in male alcoholics and controls.

The goal of this study was to assess the P3a component of event-related potentials in a population of abstinent, chronic alcoholics. A three-stimulus visual oddball paradigm was used to elicit robust P3a components in a large group of well-characterized male alcoholics (n = 44) and controls (n = 28). The task required subjects to make a difficult perceptual discrimination between randomly presented, frequently occurring vertical lines (.80) and infrequent target lines that were tilted 2 degrees to the right of vertical (.10) by only responding with a button press to the target stimuli. A nontarget infrequent horizontal line occurred (.10) randomly to which no response was made. The target stimulus elicited robust late P3b components with a parietal maximum amplitude, and the nontarget stimulus elicited reliable P3a components with a fronto-central maximum amplitude distribution. Group differences in P3a were assessed using repeated measures ANCOVA analyses in five scalp regions. Alcoholic subjects produced smaller P3a amplitudes over the central, parietal, temporal, and occipital areas compared with controls. Current source density analyses supported these findings with extension of the differences between the groups to the frontal region. The results suggest that the P3a may be important in the evaluation of alcoholism and its heritability. Theoretical implications are discussed.

Adult↗
PubMed1998

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

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

Adolescent↗
PubMed1998

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

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

Adolescent↗
PubMed1998

ERP components in category matching tasks.

The current experiment attempts to investigate (1) the effect of semantic information on the ERP correlate of visual short-term memory (VMP) and (2) the utilizing of the ERP as an objective investigative tool for the clinical observation of the existence of category-specific brain systems. Event-related potentials (ERPs) were recorded from 61 locations on the scalp of 39 healthy adults in a category (either animals or fruits/vegetables) match/non-match S1-S2 paradigm. The ERPs revealed a substantially smaller amplitude for the category matching than for non-matching pictures at the posterior brain regions, with greater activation of temporo-occipital brain regions changing from the right hemisphere at first to the left hemisphere later, as demonstrated by the current source density (CSD) maps. The ERPs elicited by the category of animal were larger than the vegetable category, similarly, the animal-animal matching condition elicited larger ERPs than did the vegetable-vegetable matching condition. In addition, the topographic distribution of the vegetable-elicited ERPs revealed additional involvement of the right frontal cortex which was absent in the topographic distribution of the animal-elicited ERPs. The spatial pattern of the VMP possesses features specific to semantic processing, and the ERPs differentiate the animal category from the vegetable category, suggesting an objective on-line method to investigate the category-specific information processing among brain-damaged patients.

Adult↗
PubMed1998

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

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

Alcoholism↗
PubMed1998

Event-related potentials during digit recognition tasks.

OBJECTIVE: An event-related potential (ERP) correlate of visual short-term memory (VMP) has been identified in our laboratory. This study aims to determine how stimulus load modulates recognition processing of digits. METHODS: ERPs were recorded from 117 healthy right-handed subjects during a delayed matching-to-sample paradigm, using number stimuli that were either low load (three digits long) or high load (five digits long). The bootstrap method [R. Srebro, A bootstrap method to compare the shapes of two scalp fields, Electroenceph. Clin. Neurophysiol. 100 (1996) 25-32.] was employed to evaluate the topographic features of the VMP revealed in the current source density (CSD) maps. RESULTS: Response times were significantly shorter for matching stimuli than for non-matching stimuli only for low loads; longer response times were related to higher loads compared to low loads only for matching stimuli. The high loads were related to larger ERP responses. The ERP was significantly smaller for matching than for non-matching three-digit numbers, but not for five-digit numbers. The ERP was also reduced to the test stimuli compared to sample stimuli regardless of stimulus load. Both temporal and frontal regions were involved in the recognition of the digit stimuli, and the left hemisphere was more active in the non-matching processing of digits. CONCLUSIONS: The VMP spatial pattern in addition to its amplitude is sensitive to stimulus load in the encoding process.

Adult↗
PubMed1998

Spatial enhancement of event-related potentials using multiresolution analysis.

Multiresolution analysis is a potentially useful tool to enhance the brain's electrical fields (spatial distributions of event-related potentials (ERP)), and to bring out spatial features which may not be seen in the fields before enhancement. For comparing different images (slices from ERP of different subjects or from the same subject but evoked by different stimuli), we define a measure (surface energy) at each decomposition scale and for different wavelets. The best wavelet and the best level for comparing the given images can be chosen based on this measure. Our experiments show that for very similar images, their difference can be brought out at some scale level. Three preprocessing steps are needed in order to carry out this wavelet analysis. First, a wavelet denoising step is needed to remove noise from the raw ERP. Secondly, a one-to-one mapping is needed to map scalp surface into a square, because the current wavelet analysis theory and algorithm are constructed on regular domains. Finally, a fitting or interpolation step is needed to construct an image on a regular grid in order to apply the fast wavelet transform algorithms.

Brain↗
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

Effects of ethanol on temporal recovery of auditory-evoked potentials in individuals at risk for alcoholism.

The present investigation examined the effects of placebo (P), low dose (LD), and high dose (HD) ethanol on auditory event-related potential (AEP) recovery functions in a group of males at high risk to develop alcoholism (HR; n = 23, mean = 22.3 years) and a low risk (LR; n = 27, mean = 23.0 years) control group. Condition order was randomized, with one condition (P, LD, or HD) per day and a minimum 1-day interval between conditions. For each subject, both blood alcohol levels (BALs) measured via breathalyzer, and event-related potentials recorded with the entire 10/20 International System, were assessed prior to and at mean intervals of 20, 60, 90, and 130 min after P, LD, or HD administration. A series of binaural auditory stimuli with randomly interposed interstimulus intervals of 0.5, 1.0, and 10.0 sec were used to elicit the N100 and P200 components of the AEP. Between-groups comparisons indicated that ethanol elicited risk group differences in recovery functions not present at baseline. The differences were manifested in the HR group as larger decrements in P200 amplitude during the ascending blood alcohol curve (acute sensitivity) and more rapid returns of both N100 and P200 to baseline levels during the descending blood alcohol curve (acute tolerance). These findings support Newlin and Thomson's (1990) Differentiator Model, suggesting that LR and HR individuals are differentially sensitive to the effects of ethanol.

Adolescent↗
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↗