Platelet serotonergic indices in major depression: up-regulation of 5-HT2A receptors unchanged by antidepressant treatment.
This study examined, in the largest sample of major depressives reported so far, platelet serotonergic parameters (5-HT uptake, [3H]paroxetine binding and 5-HT2A receptors measured by [3H]LSD binding) in 60 antidepressant-free depressed patients and 40 age- and gender-matched control subjects before treatment, and in 45 major depression patients during treatment with antidepressants. We found that, at baseline, the density (Bmax) of 5-HT2A receptors was significantly higher (by 39%) in depressed patients than in controls. Suicidal patients had significantly higher Bmax values than controls or non-suicidal patients. The rate of serotonin uptake (Vmax), but not the uptake at a single concentration, was significantly higher in depressed patients, particularly in females. There was no significant difference between the Kd or Bmax of [3H]paroxetine binding in control and depressed subjects. Treatment with antidepressant drugs of different pharmacological profile had no significant effect on the density of 5-HT2A receptors, nor did the receptor number predict the response to treatment. The affinity of serotonin uptake site for 5-HT and [3H]paroxetine significantly decreased during treatment with antidepressants, particularly SSRIs. Suppression of 5-HT uptake correlated with decreases in Hamilton depression (HAMD) scores. Our data suggest that the increased density of platelet 5-HT2A receptors may be associated with untreated major depression in antidepressant-free depressed patients, in particular those with suicidal thoughts. The persistence after antidepressant treatment and clinical improvement would suggest that up-regulation of 5-HT2A receptors is a trait rather than state phenomenon. Correlation of 5-HT uptake suppression with decreases in HAMD scores suggests that serotonin uptake inhibition is a relevant factor in antidepressant drug effect and clinical improvement.
Hrdina
P D
PD
Department of Psychiatry, University of Ottawa, Ontario, Canada.
Bakish
D
D
Ravindran
A
A
Chudzik
J
J
Cavazzoni
P
P
Lapierre
Y D
YD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000639:Amitriptyline / Q000009:adverse effects / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects*; D002352:Carrier Proteins / Q000187:drug effects*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D004316:Doxepin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D044402:Receptor, Serotonin, 5-HT2A; D011955:Receptors, Drug / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D014196:Trazodone / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000928:Antidepressive Agents; D002352:Carrier Proteins; D044402:Receptor, Serotonin, 5-HT2A; D011955:Receptors, Drug; D011985:Receptors, Serotonin; C092604:paroxetine receptor; D004316:Doxepin; D000639:Amitriptyline; D012701:Serotonin; D016666:Fluvoxamine; D014196:Trazodone