Decreased platelet serotonin transporter sites and increased platelet inositol triphosphate levels in patients with unipolar depression: effects of clomipramine and fluoxetine.
BACKGROUND
The central serotonergic system has been implicated in the pathophysiology of depression and in the mechanism of the action of antidepressant drugs. The human platelet has been proposed as a peripheral model of central serotonergic neurons.


METHODS
Six peripheral serotonergic parameters were determined simultaneously in 27 patients with unipolar depression before and after 2, 4, and 12 weeks of clomipramine or fluoxetine treatment according to the psychiatrist.


RESULTS
In patients with depression versus matched control subjects, platelet [3H]paroxetine binding sites were found to be significantly decreased (2.10 +/- 0.70 versus 3.88 +/- 0.77 fmol/10(9) platelets; P = .0001), platelet serotonin (5-HT) content was found to be significantly decreased (1.90 +/- 1.52 versus 2.74 +/- 1.12 nmol/10(9) platelets; P = .001), and platelet inositol triphosphate levels were found to be significantly increased (2.85 +/- 0.70 versus 1.85 +/- 0.77 fmol/10(9) platelets; P = .0001). No significant difference between patients and control subjects was found for platelet [3H]-lysergic acid diethylamide ([3H]LSD) binding sites, aggregation tests with 5-HT or adenosine diphosphate and plasma 5-HT levels. Treatment with both clomipramine and fluoxetine gradually further reduced the density of platelet [3H]paroxetine binding sites and induced a dramatic decrease in platelet and plasma 5-HT levels. With clomipramine, the decreased blood 5-HT levels are associated with increased platelet [3H]LSD binding sites and aggregation responses. After 12 weeks, nonresponders to both treatments had platelet inositol triphosphate levels that were still increased (2.81 +/- 0.75 fmol/10(9) platelets) when responders levels were not different from those of control subjects (1.41 +/- 0.45 versus 1.70 +/- 0.25 fmol/10(9) platelets).


CONCLUSIONS
Drug-free patients with depression had simultaneously decreased 5-HT transporter (5-HTT) sites and overstimulated phosphoinositide signaling systems. Clomipramine and fluoxetine treatments, which further decreased the density of 5-HTT sites, allowed platelet inositol triphosphate levels to return to normal values only in responders.
Alvarez
J C
JC
Service de Pharmacologie et de Psychiatrie, Faculté de Médecine Paris-Ouest et Centre Hospitalier de Versailles, Le Chesnay, France.
Gluck
N
N
Arnulf
I
I
Quintin
P
P
Leboyer
M
M
Pecquery
R
R
Launay
J M
JM
Perez-Diaz
F
F
Spreux-Varoquaux
O
O
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D002997:Clomipramine / Q000494:pharmacology*; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011985:Receptors, Serotonin / Q000097:blood*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine; D005473:Fluoxetine; D015544:Inositol 1,4,5-Trisphosphate; D017374:Paroxetine; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors