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Biomedical subjects

Sean P David

Publications and source records attributed to Sean P David.

13 recordsLinked to original sources
PubMed2006

Fellowship training in family medicine at Brown: adding depth to breadth.

The Brown Family Medicine fellowship programs share a common goal of nurturing the future leaders of our specialty. In a complex and demanding practice environment our fellowships have contributed to the development and propagation of an adept Family Medicine specialist. These fellowships endorse our specialty's broad approach to healthcare through addressing primary care and prevention, but also enhance the future of our field through melding the breadth of our discipline with the depth of expertise and the stewardship of responsible leadership.

Academic Medical Centers↗
PubMed2005

Ventral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: a functional magnetic resonance imaging study.

BACKGROUND: Converging evidence from several theories of the development of incentive-sensitization to smoking-related environmental stimuli suggests that the ventral striatum plays an important role in the processing of smoking-related cue reactivity. METHODS: Twenty-six healthy right-handed volunteers (14 smokers and 12 nonsmoking controls) underwent functional magnetic resonance imaging (fMRI) during which neutral and smoking-related images were presented. Region of interest analyses were performed within the ventral striatum/nucleus accumbens (VS/NAc) for the contrast between smoking-related (SR) and nonsmoking related neutral (N) cues. RESULTS: Group activation for SR versus N cues was observed in smokers but not in nonsmokers in medial orbitofrontal cortex, superior frontal gyrus, anterior cingulate cortex, and posterior fusiform gyrus using whole-brain corrected Z thresholds and in the ventral VS/NAc using uncorrected Z-statistics (smokers Z = 3.2). Region of interest analysis of signal change within ventral VS/NAc demonstrated significantly greater activation to SR versus N cues in smokers than controls. CONCLUSIONS: This is the first demonstration of greater VS/NAc activation in addicted smokers than nonsmokers presented with smoking-related cues using fMRI. Smokers, but not controls, demonstrated activation to SR versus N cues in a distributed reward signaling network consistent with cue reactivity studies of other drugs of abuse.

Adult↗
PubMed2005

A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans.

In humans, 5-HT1A receptors are implicated in anxiety and depressive disorders and their treatment. However, the physiological and genetic factors controlling 5-HT1A receptor expression are undetermined in health and disease. In this study, the influence of two genetic factors on 5-HT1A receptor expression in the living human brain was assessed using the 5-HT1A-selective positron emission tomography (PET) ligand [11C]WAY 100635. After the genotyping of 140 healthy volunteers to study population frequencies of known single nucleotide polymorphisms (SNPs) in the 5-HT1A receptor gene, the influence of the common SNP [(-1018) C>G] on 5-HT1A receptor expression was examined in a group of 35 healthy individuals scanned with [11C]WAY 100635. In the PET group, we also studied the influence of a common variable number tandem repeat polymorphism [short (S) and long (L) alleles] of the 5-HT transporter (5-HTT) gene on 5-HT1A receptor density. Whereas, the 5-HT1A receptor genotype did not show any significant effects on [11C]WAY 100635 binding, 5-HT1A receptor binding potential values were lower in all brain regions in subjects with 5-HTTLPR short (SS or SL) genotypes than those with long (LL) genotypes. Although the PET groups are necessarily a small sample size for a genetic association study, our results demonstrate for the first time that a functional polymorphism in the 5-HTT gene, but not the 5-HT1A receptor gene, affects 5-HT1A receptor availability in man. The results may offer a plausible physiological mechanism underlying the association between 5-HTTLPR genotype, behavioral traits, and mood states.

Adult↗
PubMed2004

Pharmacogenetics.

This article provides an introduction to the discipline of pharmacogenetics and discusses the implications of pharmacogenetics research for primary care practice. Examples are given of how genetic information can predict and inform; drug interactions influencing drug efficacy, metabolism, dosing, and toxicity. Caveats on the need for vigilance in the interpretation of pharmacogenetics studies are discussed briefly, together with the need for a convergence of biomolecular research, translational research, education,and policy to promote evidence-based genetic medicine.

Drug Design↗
PubMed2003

Does the DRD2-Taq1 A polymorphism influence treatment response to bupropion hydrochloride for reduction of the nicotine withdrawal syndrome?

Bupropion hydrochloride is effective in promoting long-term abstinence from smoking and may reduce risk for relapse through attenuation of withdrawal symptoms and craving. Bupropion is a weak dopamine reuptake inhibitor, and individual genetic variation in the dopamine D2 receptor has been associated with nicotine dependence in case-control studies. Thirty smokers were randomly assigned to bupropion or placebo and interviewed using the Minnesota Nicotine Withdrawal Scale on two occasions: prior to starting medication and after 14 days on bupropion or placebo. The individual symptoms of craving, irritability, and anxiety were significantly reduced in the bupropion group, whereas no withdrawal symptoms were diminished in the placebo group. Within the bupropion group, subgroup analyses with stratification by genotype demonstrated that craving, irritability, and anxiety were significantly attenuated only among subjects with DRD2-Taq1 A2/A2 genotypes. In the DRD2-Taq1 A1/A1 and A1/A2 groups, no significant reduction was seen in any individual symptom of the nicotine withdrawal syndrome. These data suggest that bupropion attenuates specific symptoms of the nicotine withdrawal syndrome and that this effect may be modified by genotype for the dopamine D2 receptor.

Adult↗
PubMed2002

No association between functional catechol O-methyl transferase 1947A>G polymorphism and smoking initiation, persistent smoking or smoking cessation.

Nicotine stimulates dopamine release and activates dopaminergic reward neurones in central pathways giving rise to dependence. Catechol O-methyl transferase (COMT) inactivates extraneuronally released dopamine and is present in dopaminergic brain regions. A functional polymorphism (COMT 1947A>G) resulting in increased enzyme activity has been associated with alcoholism and polysubstance abuse. We examined the relationship between the COMT 1947A>G polymorphism and smoking initiation, smoking persistence and smoking cessation. We genotyped 266 current smokers, 270 ex-smokers and 265 lifetime non-smokers (never smokers), matched for age and gender, for the COMT 1947A>G polymorphism. Smoking status was ascertained by self-report. There was no difference in genotype frequencies between never smokers and ever smokers (current + ex-smokers); between non-smokers (never + ex-smokers) and current smokers; or between current smokers and ex-smokers. These data suggest that the COMT 1947A>G polymorphism is not associated with smoking initiation, smoking persistence or smoking cessation.

Adult↗