H Begleiter

..CIDR, Affymetrix, and Illumina provided single-nucleotide polymorphism genotyping of a large subset of the COGA subjects. This article briefly describes the dataset that was provided...

..Moreover, these electrophysiological abnormalities are heritable and predictive of future alcohol abuse or dependence...

..It is concluded that the advent of genomics and proteomics and a fuller understanding of gene regulation will open new horizons on the critical electrical events so essential for human brain function...

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..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...

..There also was no evidence for unequal transmission of DRD2 alleles for the phenotypes "ever smoker" or comorbid alcohol dependence and habitual smoking. This study does not support linkage of the DRD2 with smoking...

..Identification of differences between smokers and non-smokers on basic characteristics of neurocognitive functioning may help to elucidate the mechanisms of tobacco dependence...

..The lower P3a amplitude coupled with more disorganized current source density maps suggest inefficient brain functioning in high-risk subjects...

..These data provide significant support for P300 as an endophenotype for alcohol dependence...

..The present analysis on log(M) allows more individuals to be included and thus is potentially more powerful...

..To align the repeated single trials of the event-related potential (ERP) in order to get an improved estimate of the ERP...

..The presence of these preexisting central nervous system states may lead to ethanol use for self-medication, which then may facilitate the development of both tolerance to and dependence on ethanol...

..The findings are discussed in terms of functional and physiologic significance of the P3 amplitude in alcoholic women and its relationship to drinking behaviors...

..This perhaps can be characterized by a deficient top-down processing mechanism...

..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...

..6%), whereas 45% of African Americans carry the allele (MAF 26%), which makes it a much more significant risk factor in the African American population...

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..Our results provide an illustration of the successful use of endophenotypes to identify genes involved in the predisposition to a complex psychiatric phenotype, a strategy originally proposed by Gottesman and Shields in 1972...

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..There was no association with other genes in the GABAA cluster on chromosome 4 with illicit drug dependence...

..These findings underscore the utility of electrophysiology and neurogenetics in the understanding of cognitive function and the study of brain-related disorders...

..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...

..We also obtain evidence for epistatic interaction between a region on Chromosome 1 and one on Chromosome 15. Although alcoholism as a covariate does not have any effect on the linkage scan, it has an effect on the epistatic interaction...

..Recently the genetic polymorphism most widely analyzed in DRD2, Taq1A, has been discovered to reside in a neighboring gene, ankyrin repeat and kinase domain containing 1 (ANKK1), located 10 kb downstream from DRD2...

..Other heritability patterns were also identified within each frequency band. Our results suggest that substantial proportions of the variability in the bipolar EEG measures are explained by genetic factors...

..This study assessed whether there is a relationship between impulsivity and alcohol dependence, and their correlations with P3 (P300) amplitude, a proposed endophenotype of alcoholism...

..The results from the bipolar derivations are in greater accord with genetic findings in brain anatomy and show the possibility of multiple genetic sources for the phenotypic variability of EEG activity...

..These results remain significant after taking into account alcohol dependence and depression diagnoses in the sample...

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..It is also unclear whether psychiatric comorbidity in AD subjects accounts for additional variance in frontal asymmetry, beyond a diagnosis of AD alone...

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..It is proposed that the No-Go P3, the electrophysiological signature of response inhibition, can be considered as an endophenotypic marker in alcoholism...

..SIGNIFICANCE: Dysfunctional neural and response inhibition in the offspring of alcoholics perhaps provides an endophenotypic marker of risk for the development of alcoholism and related disorders...

..The utility of these neuroelectric measures as endophenotypes for psychiatric genetics is evaluated...

..Uncovering the genes influencing brain oscillations provides a better understanding of the neural function involved in information processing...

..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...

..Activation of thalamus, insula, and the occipitotemporal cortex has been reported less consistently. The present study lends further support to the involvement of these structures in visual target detection...

..Applying principal component analysis in the COGA sample provided support for some regions of linkage previously reported in COGA, and identified other new, promising regions of linkage...

..The advent of genomics and proteomics and a fuller understanding of gene regulation, will open new horizons on the critical electrical events so essential for human brain function...

..This feature is more prominent in male alcoholics. The increased beta power in the resting EEG may be an electrophysiological index of the imbalance in the excitation-inhibition homeostasis in the cortex...

..Parametric and non-parametric analyses show differences in the complexity data which are significant between the control group and the alcoholic and high-risk groups...

..ERP topographic features are more sensitive than amplitude measurements in assessing alcoholic-related modality effects...

..Genetic analyses have identified regions on several chromosomes that are associated with these phenotypes and need to be studied further...

..Finally, there is also evidence of an area on chromosome 2 that may reflect a common genetic vulnerability locus to both habitual smoking and alcohol dependence...

..This finding indicates that a dysfunctional frontoparietal circuit may underlie the low P300 responses seen in HR subjects. This perhaps implies a deficiency in the rehearsal component of the working memory system...

..These differences are consistent with an imbalance between excitation and inhibition processes in the brains of alcoholics...

..A neuro-cognitive model has been provided to explain the findings. It is suggested that the oscillatory correlates during cognitive processing can be an endophenotypic marker in alcoholism...

..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...

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..The results indicate that increased EEG beta power can be considered as a likely marker of risk for developing alcoholism and may be used as a predictive endophenotype...

..Both linkage and association to the region on chromosome 15q that contains a cluster of GABAA receptor genes have previously been reported, but the role of these genes in alcoholism remains inconclusive...

..These findings provide strong evidence that variants within or close to the CHRM2 locus influence risk for two common psychiatric disorders...

..01) There was weaker evidence that variations in ADH1A and ADH1B might also play a role in modifying risk. Among African-Americans, there was evidence that the ADH1B*3 allele was protective...

..Alcoholic subjects have low levels of dopamine D(2) receptors in striatum, and increasing D(2) receptor levels in laboratory animals reduces alcohol consumption...

..While regressing out the effect of alcoholism does not affect the linkage findings, the epistatic interactions become statistically insignificant...

..It is likely that the theta power increase is a trait-related phenomenon and is expressed to differing degrees in the two genders...

..GABRA2 is also associated with other drug dependence in our sample, both in adolescence and adulthood...

..Family density effects further support the evidence that these findings are heritable. These results suggest that P3 can be considered as a phenotypical marker of vulnerability to alcoholism in women...

..The electrophysiological results obtained from this application may find that aspects of brain dysfunction (i.e. lack of differential inhibition) may be involved in a predisposition for alcoholism. ..

..Finally, the eighth IRPG site (Rutgers University) will be responsible for DNA extraction and cell lines, as well as a major repository. ..

..We propose to identify brain oscillations that are predictive of relapse and explore the role of neurophysiological features of CNS disinhibition in predicting relapse in alcoholic patients ..

..We also plan to retest these patients one year after the initial studies. We propose to conduct parallel studies with neurological patients who have unilateral lesions in either frontal cortex or parietal cortex...

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