5-HT2A receptor binding is reduced in drug-naive and unchanged in SSRI-responder depressed patients compared to healthy controls: a PET study
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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).
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 [18F]fluoroethylspiperone ([18F]FESP), a 5-HT2A and D2 receptor antagonist. A "binding index" (BI) of [18F]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).
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.
The reduction of [18F]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. [18F]FESP cortical BI may represent a state marker of depression.
KeywordsMajor depression Serotonin receptors Emission tomography Antidepressant
The authors wish to thank Dr. Francesco Perugini, Mr. Giuseppe Striano, Mrs. Carmen Nichetti and Mrs. Lorena Bonaldi for their help in the study and Professor P.M. Grasby for useful advise and discussion. Grant supporting: Fondo de Investigatión Sanitaria 98/697 (professor Artigas).
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