Amygdala response to smoking-cessation messages mediates the effects of serotonin transporter gene variation on quitting

Abstract

The amygdala is critically involved in detecting emotionally salient stimuli and in enhancing memory for emotional information. Growing evidence also suggests that the amygdala plays a crucial role in addiction, perhaps by strengthening associations between emotionally-charged drug cues and drug-seeking behavior. In the current study, by integrating functional MRI (fMRI), genetics, and outcome data from a large group of smokers who completed a smoking-cessation intervention and attempted to quit, we show that the amygdala also plays a role in quitting. Specifically, we demonstrate that the amygdala response to smoking-cessation messages in smokers trying to quit is a predictor of their post-intervention quitting outcome. We further show that the amygdala response is modulated by genetic variation in the serotonin transporter and mediates the impact of this genetic variation on quitting. These results point to a gene-brain-behavior pathway relevant to smoking cessation, and add to our understanding of the role of the amygdala in nicotine addiction.

Figure 1

Mean amygdala response to tailored smoking-cessation messages mediates the impact of STin2 genotype on smoking cessation. A. Anatomically defined region-of-interest masks for right and left amygdala shown against MNI 152 template. B. Mediation path diagram. Lines are labeled with unstandardized B coefficients, with standard errors in parentheses. Path b denotes the association of the mean amygdala response with smoking cessation, controlling for the effects of STin2 genotype. Direct effect c′ denotes the effect of STin2 genotype on smoking cessation, controlling for the mediation effect. *p < 0.05.

Figure 2

Mean amygdala response to untailored smoking-cessation messages mediates the impact of STin2 genotype on smoking cessation. A. Anatomically defined region-of-interest masks for right and left amygdala shown against MNI 152 template. B. Mediation path diagram. Lines are labeled with unstandardized B coefficients, with standard errors in parentheses. Path b denotes the association of the mean amygdala response with smoking cessation, controlling for the effects of STin2 genotype. Direct effect c′ denotes the effect of STin2 genotype on smoking cessation, controlling for the mediation effect. *p ≤ 0.05.

Figure 3

The right amygdala is a global maximum in a voxel-wise search for brain regions whose response to tailored smoking-cessation messages (A) and untailored smoking-cessation messages (B) is modulated by the STin2 genotype (thresholded at p = 0.005, 10 contiguous voxels). The results are shown against the MNI template brain. The scale represents t values.