Enhanced smoking cue salience associated with depression severity in nicotine-dependent individuals: a preliminary fMRI study.

The association between cigarette smoking and depression has been well documented; however, little research has been done to elucidate the neurobiological substrates of this highly prevalent comorbidity. We used multiple linear regression analysis to evaluate the relationship between depression severity as assessed by the Hamilton Depression Rating Scale (HAMD) and blood oxygen level-dependent (BOLD) responses to visual smoking cues in drug-free nicotine-dependent smokers (n=18). Two functional magnetic resonance imaging (fMRI) scans were completed over a single study day, following overnight smoking abstinence (pre-smoking scan) and after cigarette reinstatement (post-smoking scan). During the pre-smoking scan positive correlations between BOLD activity and HAMD scores were observed in areas of the mesocorticolimbic dopaminergic system [inferior frontal gyrus, middle frontal gyrus (MFG), hippocampus (HC), anterior cingulate gyrus] and areas of the visuospatial attention circuit (medial occipital lobe, middle cingulate cortex, superior frontal gyrus, angular gyrus). During the post-smoking scan positive correlations were observed in areas of the brain implicated in drug expectancy (MFG), memory (HC), attentional motivation (posterior cingulate cortex), and visual processing and attention (precuneus). These preliminary findings demonstrate that smokers with higher depression severity attribute greater incentive salience to smoking-related cues and this is especially pronounced during periods of acute abstinence. Such enhanced salience of smoking cues, even after smoking a cigarette, may play a critical role both in the maintenance of smoking in depression and in greater levels of nicotine dependence seen in this patient population.