Dopaminergic activity in depressed smokers: a positron emission tomography study

Abstract

Tobacco dependence is highly prevalent in depressed patients. We assessed changes in [(11)C]-raclopride binding potential (BP) using positron emission tomography (PET) before and after the oral administration of d-amphetamine in healthy controls and unmedicated patients with current depression with and without current tobacco dependence. Over a single study day 2 [(11)C]-raclopride positron emission tomography scans were taken in 38 subjects: at baseline and 2 h following oral d-amphetamine 30 mg. Twenty controls (9 smokers, 11 nonsmokers) and 18 subjects with current major depressive episode (8 smokers, 10 non-smokers). Striatal [(11)C]-raclopride binding potential was measured before and after d-amphetamine administration. Depressed smokers had a lower baseline [(11)C]-raclopride binding potential compared with both control non-smokers (P < 0.007) and depressed non-smokers (P < 0.001). There was a main effect of smoking status on amphetamine-induced change in [(11)C]-raclopride binding potential (P < 0.02), but no main effect of depression. This may be due to a floor effect because of the low BP at baseline. Depressed subjects reported significant increase of positive mood after d-amphetamine administration compared with controls (depressed smokers vs. control smokers: P < 0.05; depressed non-smokers vs. controls: P < 0.055). Tobacco dependence appears to decrease d-amphetamine-induced changes in [(11)C]-raclopride binding potential as measured by positron emission tomography. Comorbid major depression and tobacco dependence exacerbates this effect, suggesting an altered dopamine system in comorbid patients.

Fig 1. Correlation between baseline [¹¹C]-raclopride BP and age for the four subject groups

Control NS = control non-smokers, Control Sm = control smokers, MDD NS = depressed non-smokers, MDD Sm = depressed smokers. There was an overall significant correlation (r = −0.5; p < 0.05) and a significant correlation in the control smoker group only (r= −0.7; p < 0.01).

Fig 2. [¹¹C]-raclopride binding potential (BP) post-amphetamine administration expressed as a percentage of [¹¹C]-raclopride BP at baseline among the four subject groups

Control NS = control non-smokers, Control Sm = control smokers, MDD NS = depressed non-smokers, MDD Sm = depressed smokers. * denotes a significant difference (p=0.03) between control non-smokers and depressed smokers and + denotes a significant difference (p=0.01) between depressed non-smokers and depressed smokers. The ⚊ denotes the mean.

Fig 3. Subjective effects of d-amphetamine measured using visual analog scales (VAS)

Data were consolidated into positive drug effects (e.g., “high”, alert) and negative drug effects (e.g., irritable, restless) and are presented as the mean of the peak score minus the baseline score. * = significantly different from control non-smokers (p < 0.05), ** = significantly different from MDD non-smokers (p < 0.01)