Neural correlates of attentional bias for smoking cues: modulation by variance in the dopamine transporter gene

Smoking cue reactivity - all smokers

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Smoking cue reactivity - 9-repeats

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Smoking cue reactivity - 10/10-repeats

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Smoking cue reactivity - 9-repeats vs. 10/10-repeats

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Attentional Bias Correlates - 9-repeats

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Attentional Bias Correlates - 10/10-repeats

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Attentional Bias Correlates - 9-repeats vs. 10/10-repeats

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Region of Interest Mask

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Abstract

AUTHORS: *Reagan R. Wetherill1, Kanchana Jagannathan1, Falk W. Lohoff1, Ronald Ehrman2, Charles P. O'Brien1,Anna Rose Childress1, & Teresa R. Franklin1

1University of Pennsylvania, Department of Psychiatry, Philadelphia, PA 19104, USA
2Philadelphia VA Medical Center, Philadelphia, PA 19104, USA

* Corresponding author: Reagan R. Wetherill, Ph.D.
University of Pennsylvania, Department of Psychiatry
3900 Chestnut Street, Philadelphia, PA 19104, USA
Telephone: (215) 222-3200 ext. 141
Fax: (215) 386-6770
Email: rwetherill@mail.trc.upenn.edu


ABSTRACT

Cigarette-dependent smokers automatically and involuntarily orient attention towards 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 (pCASL) perfusion fMR images were acquired during SC exposure in 35 smokers genotyped for the SLC6A3 variable number of tandem repeats (VNTR) 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.