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A human tryptophan hydroxylase intron seven polymorphism previously associated with low CSF 5-HIAA and suicidal behavior was sequenced and characterized for its potential role in TPH pre-mRNA splicing. Two polymorphic sites were identified: A218C and A779C. The 779A allelic frequency in various populations ranged from 0.43 to 0.61 and was in strong linkage(More)
Genetic variation may partially underlie complex personality and physiological traits--such as impulsivity, risk taking and stress responsivity--as well as a substantial proportion of vulnerability to addictive diseases. Furthermore, personality and physiological traits themselves may differentially affect the various stages of addiction, defined(More)
Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify genetic variants that are associated with susceptibility to develop heroin addiction by analyzing 1350 variants in 130 candidate genes. All subjects had Caucasian ancestry. The sample consisted of 412 former severe heroin addicts in(More)
Opiate and cocaine addictions are major social and medical problems that impose a significant burden on society. Despite the size and scope of these problems, there are few effective treatments for these addictions. Methadone maintenance is an effective and most widely used treatment for opiate addiction, allowing normalization of many physiological(More)
Alterations in the expression of multiple genes in many brain regions are likely to contribute to psychostimulant-induced behaviours. Microarray technology provides a powerful tool for the simultaneous interrogation of gene expression levels of a large number of genes. Several recent experimental studies, reviewed here, demonstrate the power, limitations(More)
Dynorphin peptides and the kappa-opioid receptor are important in the rewarding properties of cocaine, heroin, and alcohol. We tested polymorphisms of the prodynorphin gene (PDYN) for association with cocaine dependence and cocaine/alcohol codependence. We genotyped six single nucleotide polymorphisms (SNPs), located in the promoter region, exon 4 coding,(More)
The most common single nucleotide polymorphism in the coding region of the human mu opioid receptor gene is the A118G variant, an adenine to guanine transition at nucleotide position 118 of the coding sequence of the gene. This polymorphism codes for an asparagine to aspartic acid substitution at amino acid 40 in the amino-terminus, thereby removing a(More)
Drug addiction is a complex disorder that has a large spectrum of causes. Vulnerability to addiction has been shown in twin studies to have a robust genetic component. This genetic basis for addiction has general and specific components for each drug abused. Although many genes have been implicated in drug addiction, only a handful have either been(More)
BACKGROUND To examine whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme in the biosynthesis of serotonin, may be a factor influencing serotonin turnover and behaviors controlled by serotonin. METHODS Using a polymerase chain reaction-based method, TPH genotype was determined in DNA samples from 56 impulsive and 14(More)
To assess the relationship between two phenotypes in an extremely well-characterized population of personality disorder patients-impulsive aggression and prolactin response to fenfluramine-and tryptophan hydroxylase (TPH) genotype, TPH genotype (at an intronic polymorphic site) and prolactin response to fenfluramine were assessed in 40 Caucasian patients(More)