5-HT(2A) receptor binding is reduced in drug-naive and unchanged in SSRI-responder depressed patients compared to healthy controls: a PET study.
OBJECTIVE
The aim of the study was to investigate differences in 5-HT(2A) 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 [(18)F]fluoroethylspiperone ([(18)F]FESP), a 5-HT(2A) and D(2) receptor antagonist. A "binding index" (BI) of [(18)F]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 [(18)F]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-HT(2A) receptors. [(18)F]FESP cortical BI may represent a state marker of depression.
Messa
Cristina
C
CNR Institute of Molecular Imaging and Physiology, Istituto Scientifico S. Raffaele, University of Milan-Bicocca, University of Milan, Milan, Italy. cristina.messa@hsr.it
Colombo
Cristina
C
Moresco
Rosa Maria
RM
Gobbo
Clara
C
Galli
Laura
L
Lucignani
Giovanni
G
Gilardi
Maria Carla
MC
Rizzo
Giovanna
G
Smeraldi
Enrico
E
Zanardi
Raffaella
R
Artigas
Francesc
F
Fazio
Ferruccio
F
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000378:metabolism / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000378:metabolism / Q000627:therapeutic use*; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism; D014055:Tomography, Emission-Computed
D018687:Antidepressive Agents, Second-Generation; D018492:Dopamine Antagonists; D005462:Fluorine Radioisotopes; D008024:Ligands; D017374:Paroxetine; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013134:Spiperone; C051175:3-N-(2-fluoroethyl)spiperone