Dopaminergic activity in depressed smokers: A positron emission tomography study

Tobacco dependence is highly prevalent in depressed patients. We assessed changes in [¹¹C]‐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 [¹¹C]‐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 [¹¹C]‐raclopride binding potential was measured before and after d‐amphetamine administration. Depressed smokers had a lower baseline [¹¹C]‐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 [¹¹C]‐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 [¹¹C]‐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.