Neural correlates of attentional bias for smoking cues: modulation by variance in the dopamine transporter gene.
Cigarette-dependent smokers automatically and involuntarily orient attention toward smoking cues (SCs). This attentional bias is clinically significant, as it may contribute to relapse. Thus, identifying neural and genetic correlates of attentional bias is critical for improving interventions. Our previous studies show that the dopamine transporter (DAT) SLC6A3 genotype exerts profound effects on limbic responses to SCs. One potential mechanism underlying these effects is greater attentional bias for SCs. Here, we explored associations between attentional bias for SCs and neural responses to SCs among 'sated' smokers genotyped for the SLC6A3 polymorphism. Pseudo-continuous arterial spin-labeled perfusion functional magnetic resonance imaging images were acquired during SC exposure in 35 smokers genotyped for the SLC6A3 variable number of tandem repeats polymorphism (n = 16, 9-repeats; n = 19, 10/10-repeats). Participants completed a visual dot-probe attentional bias task, which contained pictures of smoking and non-smoking pictures, to examine whether genetic variation in DAT influences attentional bias and to investigate relationships between attentional bias and neural responses to SCs. Although attentional bias to smoking pictures was not significantly different between 9-repeats and 10/10-repeats, 9-repeats showed a positive correlation between attentional bias and increased SC-induced brain activity in the amygdala, whereas 10/10-repeats showed an inverse correlation in the medial orbitofrontal cortex (mOFC). In group comparisons, 9-repeats exhibited positive correlations between attentional bias and SCs in the mOFC and amygdala, relative to 10/10-repeats. Findings suggest that genetic variation in the DAT gene influences brain responses associated with attentional bias; thus, providing additional support for a SC-vulnerable endophenotype.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Reagan R
RR
Wetherill
Kanchana
K
Jagannathan
Falk W
FW
Lohoff
Ronald
R
Ehrman
Charles P
CP
O'Brien
Anna Rose
AR
Childress
Teresa R
TR
Franklin
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000503:physiopathology*; D001288:Attention / Q000502:physiology*; D002540:Cerebral Cortex / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D003463:Cues; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000706:statistics & numerical data; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010775:Photic Stimulation / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics; D011930:Reaction Time / Q000502:physiology; D012008:Recurrence; D012907:Smoking / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D020080:Tandem Repeat Sequences / Q000235:genetics; D055815:Young Adult
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human