DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues.
BACKGROUND
A dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism has been related to reactivity to smoking cues among smokers, but the effect of this genetic variation on brain responses to smoking cues has not been evaluated.


OBJECTIVE
The present study evaluated the relationship between carrying the DRD4 VNTR 7-repeat allele and transient functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent responses to smoking cues among adult dependent cigarette smokers.


METHODS
Smokers (n = 15) underwent fMRI scanning after 2-h abstinence. During scanning, they viewed visual smoking and control cues. A blood sample was assayed for the DRD4 VNTR polymorphism, and participants were categorized based on whether they carried one or two copies of the 7-repeat allele (DRD4 L, n = 7) or not (DRD4 S, n = 8).


RESULTS
Contrasts in brain cue-reactivity (smoking minus control cues) between DRD4 groups were conducted using SPM2. Smoking cues as compared to control cues elicited transient brain responses in right superior frontal gyrus (BA 8/9/10/32), left anterior cingulate gyrus (BA 32), and right cuneus (BA 19). Exposure to smoking cues resulted in greater activation of right superior frontal gyrus (BA 10) and right insula in DRD4 L compared to DRD4 S individuals. By contrast, exposure to smoking cues among DRD4 S individuals resulted in no significant increases in activation compared to DRD4 L individuals.


CONCLUSIONS
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.
McClernon
F Joseph
FJ
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27708, USA. mccle011@mc.duke.edu
Hutchison
Kent E
KE
Rose
Jed E
JE
Kozink
Rachel V
RV
D000328:Adult; D002248:Carbon Monoxide / Q000097:blood; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000502:physiology; D003463:Cues; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000502:physiology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic; D011859:Radiography; D050638:Receptors, Dopamine D4 / Q000235:genetics* / Q000502:physiology; D012907:Smoking / Q000523:psychology*; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D011795:Surveys and Questionnaires; D014029:Tobacco Use Disorder / Q000235:genetics / Q000503:physiopathology / Q000523:psychology
C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4; D002248:Carbon Monoxide