Objective: The aim of the study was to investigate differences in 5-HT2A receptor binding between healthy volunteers and patients with major depressive disorder (MDD), either never treated before with antidepressants (drug-naive: DN) or responding to paroxetine treatment (drug-treated: DT). Methods: Nineteen DN patients with MDD and 15 euthymic DT (paroxetine 4 weeks) patients were compared with a group of 20 healthy controls (C) with positron emission tomography (PET) using [F-18]fluoroethylspiperone ([F-18]FESP), a 5-HT2A and D-2 receptor antagonist. A "binding index" (BI) of [F-18]FESP to cortical and basal ganglia regions was calculated as the ratio of the activity in these regions to that of cerebellum. Differences in BI between groups, i.e. C versus DN or DT, were assessed by ANOVA, with or without age as covariate (ANCOVA). Results: A significant reduction in BI (P=0.003 ANOVA, P=0.001 ANCOVA) was found in DN patients in the frontal, occipital, temporal and cingulate cortices, but not in the striatum. No significant differences emerged between C and DT patients. Conclusions: The reduction of [F-18]FESP BI in cortical areas of DN depressed, but not of euthymic DT patients suggests an association between the occurrence of depressive symptoms and impairment of cortical 5-HT2A receptors. [F-18]FESP cortical BI may represent a state marker of depression.
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