Dopaminergic activity in depressed smokers: A positron emission tomography study

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. Synapse 63:681–689, 2009. © 2009 Wiley‐Liss, Inc.