Reduction
of cortical 5-HT2A receptor binding
in drug-naive but not in paroxetine-responder
depressed patients
Many
studies have suggested that 5-HT2A
receptors are involved in the pathophysiology of
depression and that an association may exist
between clinical improvement and binding to
these receptors. Changes in their density have,
however, yielded conflicting results. Among the
factors which may contribute to these
discrepancies is the absence of a direct
comparison between depressed subjects and
healthy controls. A study was thus designed to
compare 5-HT2A receptor binding
between patients with major depressive disorder
(MDD), either never treated with antidepressants
(drug-naive, DN) or responding to the selective
serotonin reuptake inhibitor, paroxetine
(drug-treated, DT), and healthy volunteers.
Among 34 patients diagnosed with MDD, 19 had
never been treated with any antidepressant drug
and 15 were in their 4th week of treatment with
paroxetine. These subjects were compared with a
group of 20 heathy controls. Positron emission
tomography (PET) with
[18F]fluoroethylspiperone
([18F]FESP), a
5-HT2A receptor antagonist and
dopamine D2 receptor antagonist, was
used and a binding index (BI) of
[18F]FESP to cortical
(serotonergic) and striatal (dopaminergic)
regions was calculated as the ratio of binding
in these regions compared to that of cerebellum
(considered to represent background "noise".
Binding was reduced in naive patients in the
frontal, occipital, temporal and cingulate
cortices, but not in the striatum. BI values of
the whole cortex of these these subjects were
reduced by 23% compared to those of normal
controls. No differences were found between
treated patients and healthy controls.
These results lend support to a relationship
between depressive symptoms and the decrease of
5-HT2A receptor binding. In addition
a return to normal binding value would explain
the unaltered binding value in patients
responding to paroxetine.
[18F]FESP binding to cortical
regions may be useful to detect state-related
changes in depression and therefore represent a
depression marker. Psychopharmacology
167: 72-78, 2003