PubMed · 15318129
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Mark Gillman, Fred Lichtigfeld. 2004. An incorrect technique guarantees failure.. https://doi.org/10.1097/01.alc.0000133393.27278.c6
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Dorsal striatum is regulated by the serotonergic system, and it is a brain area with a role in the development of obsessive thought patterns, which may be related to addiction. In this study, possible alterations of [(3)H]citalopram binding to serotonin transporter (SERT) were evaluated in the dorsal striatum of Cloninger type 1 and 2 alcoholics, and nonalcoholic control subjects by postmortem whole-hemisphere autoradiography in humans. The SERT binding was significantly lower (-26%, effect size 1.74) in the caudate body of alcoholics. The SERT binding tended to be lower also in the other parts of the dorsal striatum in alcoholics, but the results did not reach significance. In addition, there was a significant positive correlation, especially in type 1 alcoholics, between the SERT binding in the body of the caudate and in the perigenual anterior cingulate cortex, an area in which the SERT binding has been shown to be lower among alcoholics. These results give preliminary evidence to suggest that the SERT binding in the dorsal striatum may be lower in alcoholics, and that the serotonergic system may be affected in cortical and striatal areas simultaneously. The cortico-striatal-thalamic axis may have an important role in fully developed addictions and the characterization of these correlations within the serotonergic system may lead to a better understanding of the anatomical dynamics underlying the neurochemistry of alcoholism.
OBJECTIVE: To extract the relevant SNPs for alcoholism using sib-pair IBD profiles of pedigrees. METHODS: We used the ensemble decision approach, a supervised learning approach based on decision forests, to locate alcoholism relevant SNPs using genome-wide SNP data. RESULTS: Application to a publicly available large dataset of 100 simulated replicates for three American populations (http://www.gaworkshop.org/) demonstrates that the proposed approach has successfully located all of the simulated true loci. CONCLUSION: The numerical results establish the proposed decision forest analysis to be a powerful and practical alternative for large-scale family-based association study.
OBJECTIVE: To develop novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context. METHODS: In the proposed strategies, we define four relevancy criteria for mapping SNP-phenotype relationships-point-wise IBD mean difference, averaged IBD difference for window, Z curve and averaged slope for window. RESULTS: Application of these criteria and permutation test to 100 simulated replicates for two hypothetical American populations to extract the relevant SNPs for alcoholism based on sib-pair IBD profiles of pedigrees demonstrates that the proposed strategies have successfully identified most of the simulated true loci. CONCLUSION: The data mining practice implies that IBD statistic and genomic context could be used as the informatics for locating the underlying genes for complex human diseases. Compared with the classical Haseman-Elston sib-pair regression method, the proposed strategies are more efficient for large-scale genomic mining.