Fifty-six otherwise healthy adult (21 to 65 years old) cigarette smokers either with (n = 10) or without (n = 46) a history of Major Depressive Disorder (MDD+ and MDD−, respectively) completed the study. Findings from the MDD− smokers were published recently (10
), and inclusion/exclusion criteria, screening procedures, rating scales, and all PET and magnetic resonance imaging (MRI) scanning methodology were the same here as in our previous reports (8
), except that one study group here consisted of a preliminary sample of MDD+ subjects who had not had an acute episode of MDD meeting DSM-IV criteria (11
) for at least six months prior to study participation.
Participants underwent bolus-plus-continuous-infusion 11C-raclopride PET scanning for 90 mins, during which they smoked a regular cigarette (favorite brand) outside the scanner between minutes 50 and 60. Demographic and other clinical variables were collected before scanning, and symptoms of tobacco withdrawal and smoking characteristics (Clinical Research Support System device, Plowshare, Baltimore, MD) were monitored during scanning. A structural MRI scan was obtained within one week of PET scanning to aid in brain region localization. Each participant received a description of the study, and gave written informed consent, using forms approved by the local IRB, before scanning.
While no MDD+ subjects met DSM-IV criteria for an acute depressive episode, these subjects did report between mild depressive symptoms (range − 1 to 4) at the time of PET scanning. Four subjects were taking antidepressants (stable dose > 2 months; 2 taking serotonin reuptake inhibitors, 1 taking venlafaxine, and 1 taking bupropion).
To verify similarities in demographic and rating scale variables between groups at baseline, unpaired Student t-tests and a Chi-Square test (for gender) were performed. To compare groups in clinical responses to smoking during scanning, unpaired Student t-tests were performed for changes in withdrawal symptoms from before to after smoking.
For PET data, changes in 11
C-raclopride binding potential (BPND
) from before to after smoking were compared between groups with an ANCOVA, with BPND
percent change as the dependent measure, group (MDD+ vs. MDD−) as the between-subject factor, and age, gender, and total cigarette puff volume as covariates. Even though the groups did differ significantly in these covariates (see results below), these variables were included in the analysis, because of prior reports linking them with differences in DA system function (see (10
) for review information). Because of concern that taking an antidepressant might affect smoking-induced DA release, an ANCOVA with the same design as above was also run excluding those MDD+ subjects who were taking an antidepressant at the time of scanning.
For the MDD+ group, Pearson Product Moment Correlation Coefficients were determined between BPND percent change and pre-smoking Hamilton Depression and Anxiety (HAM-D and HAM-A) Scale scores, to establish if baseline depression and anxiety levels were associated with smoking-induced DA concentration change. Correlation coefficients were also determined between BPND percent change and percent change in craving (Urge to Smoke [UTS] scale), state anxiety (Spielberger State Trait Anxiety Index [STAI]), and mood analog scores with smoking, to determine relationships between DA concentration change and withdrawal alleviation. Statistical tests were performed with SPSS version 16.0 (SPSS; Chicago, IL).