Platelet serotonergic indices in major depression: up-regulation of 5-HT2A receptors unchanged by antidepressant treatment

Psychiatry Res. 1997 Feb 7;66(2-3):73-85. doi: 10.1016/s0165-1781(96)03046-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amitriptyline / adverse effects
  • Amitriptyline / therapeutic use
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Blood Platelets / drug effects*
  • Carrier Proteins / drug effects*
  • Depressive Disorder / blood
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Doxepin / adverse effects
  • Doxepin / therapeutic use
  • Female
  • Fluvoxamine / adverse effects
  • Fluvoxamine / therapeutic use
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Personality Inventory
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Drug / drug effects*
  • Receptors, Serotonin / drug effects*
  • Serotonin / physiology*
  • Trazodone / adverse effects
  • Trazodone / therapeutic use
  • Treatment Outcome


  • Antidepressive Agents
  • Carrier Proteins
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Drug
  • Receptors, Serotonin
  • paroxetine receptor
  • Doxepin
  • Amitriptyline
  • Serotonin
  • Fluvoxamine
  • Trazodone