DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues

McClernon, F. Joseph; Hutchison, Kent E.; Rose, Jed E.; Kozink, Rachel V.

doi:10.1007/s00213-007-0860-6

Cited by 82 publications

(78 citation statements)

References 59 publications

(78 reference statements)

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“…Our results concur with some [17,20,23,34,38], but disagree with other [6,11,18,24,29] results. Although there are findings showing an association of long DRD4 gene allele and smoking only in men [17], the majority of previous studies did not find sex differences in the distribution of long and short alleles [6,24,34] and our data are in line with these findings.…”

Section: Discussionsupporting

confidence: 63%

“…The influence of VNTR in the third exon of DRD4 gene on the brain of smokers is confirmed with neuroimaging findings. Differential activation of brain parts was observed for smokers, long and short allele carriers, after exposure to different smoking-related cues [29]. This study was performed on 15 smokers from USA.…”

Section: Discussionmentioning

confidence: 98%

“…Long allele carriers had a greater activity in brain areas involved in response to urge (right frontal gyrus and right insula). It was assumed that in these brain areas DRD4 receptors are expressed in high amount [29]. In Caucasian subjects, long allele carriers who smoked, needed more time for solving the Stroop test after the exposure to smoking-related cues, than smokers which were DRD4 gene short allele carriers [24].…”

Section: Discussionmentioning

confidence: 99%

“…The results showing the association between nicotine addiction and DRD4 VNTR are conflicting. No association between DRD4 VNTR polymorphism and smoking [17,20,23,34,38], or significant association between DRD4 VNTR and nicotine dependence [6,11,18,24,29] was previously reported.…”

Section: Introductionmentioning

confidence: 92%

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Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking

Babić

Nedić

Mück‐Šeler

et al. 2012

Neuroscience Letters

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

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Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking

Babić

Nedić

Mück‐Šeler

et al. 2012

Neuroscience Letters

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“…A majority of studies have focused on genetic variation in the dopamine system. For example, the 7-repeat allele of a common variable number tandem repeat (VNTR) in the dopamine D4 receptor (DRD4) gene, associated with decreased dopaminergic tone and increased craving (Hutchison et al, 2002), is associated with enhanced cue reactivity in drug reward-related regions among alcohol drinkers and regular smokers (McClernon et al, 2007;Filbey et al, 2008). The SNCA rs2583985 A allele, which may alter alpha synuclein expression in dopaminergic neurons, was also associated with increased cue reactivity in heavy drinkers (Wilcox et al, 2013).…”

Section: Cue Reactivity Assessed With Fmri or Perfusion Mrimentioning

confidence: 99%

Neuroimaging in Psychiatric Pharmacogenetics Research: The Promise and Pitfalls

Falcone

Smith

Chenoweth

et al. 2013

Neuropsychopharmacol

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The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype Â drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment.

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Genetics of Nicotine Addiction

Bloom

Goate

2014

Encyclopedia of Life Sciences

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Diseases associated with addiction to nicotine, the key reinforcing constituent of tobacco, remain the largest cause of preventable death worldwide. Although twin studies indicate a large genetic contribution to the variation in smoking‐related behaviours, the polymorphisms underlying this heritability remain largely unidentified. Candidate gene studies have investigated several pathways, but thus far only those few genetic loci identified in unbiased genome‐wide association studies have been consistently replicated; these are the direct targets of nicotine in the nervous system, the nicotinic acetylcholine receptor subunit genes CHRNA5–CHRNA3–CHRNB4 and the primary nicotine metabolism gene CYP2A6 . These variants may differ in their influences regarding different aspects of smoking behaviour, and their frequencies vary widely among different ethnic populations. Use of more‐targeted phenotypes including biomarkers of smoke exposure such as cotinine, nicotine's major metabolite, and exhaled carbon monoxide, may provide the key to detecting further genetic correlates of nicotine dependence and related diseases. Key Concepts: Variation in nicotine addiction‐related traits have large genetic components. Genetic studies of nicotine addiction seek to identify drug targets for smoking cessation treatment and to improve treatments using genotype‐based personalised medicine. Candidate gene studies have focussed on the nicotinic acetylcholine receptors and genes in the nicotine metabolism, dopaminergic, serotonergic, GABAergic, and opioid pathways, but few associations have been convincingly replicated. Unbiased genome‐wide studies have identified very few consistent genetic associations with smoking‐related phenotypes. A functional variant in the CHRNA5–CHRNA3–CHRNB4 gene cluster is robustly associated with multiple smoking behaviours and related disease risk. Functional variation in the CYP2A6 nicotine metabolism gene is associated with cigarette consumption and related disease risk. Genetic factors contributing to nicotine addiction vary by ethnic population. Genotype–environment and genotype–treatment interactions are important factors determining smoking initiation, dependence and cessation outcomes. Use of biomarkers and other endophenotypes may provide greater power to identify genetic correlates of nicotine dependence.

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DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues

Abstract: These brain imaging results suggest that DRD4 VNTR polymorphism is related to transient brain responses to smoking cues in regions subserving executive and somatosensory processes.

Cited by 82 publications

References 59 publications

Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking

Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking

Neuroimaging in Psychiatric Pharmacogenetics Research: The Promise and Pitfalls

Genetics of Nicotine Addiction

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