The Current Status of the Platelet 5-HT(2A) Receptor in Depression

The author reviews the current status of the platelet serotonin (5-HT)(2A) receptor in depression. Considered are studies of receptor binding, and 5-HT-induced platelet activation and aggregation. 5-HT(2A) receptor density tends to increase in depression, although this more clearly relates to suicidality than depression per se. Indeed, data are consistent with the hypothesis that increased density of platelet 5-HT(2A) receptors may be a marker for increased risk of suicide. 5-HT-induced calcium mobilization is enhanced in unipolar depression; however, unlike in bipolar depression, baseline calcium levels are not. Despite inconsistencies, 5-HT-induced aggregation appears inhibited in depression. This may manifest as a relative inhibition, i.e. no change in aggregation response despite a higher density of 5-HT(2A) receptors. The inhibited aggregation response is state dependent, and acute phase proteins or components of the stress response may be factors. It is unclear if differences between depressed and normal subjects in disposition of 5-HT(2A) receptors are generally indicative of traits or states. Nonetheless, there is little evidence that the degree of departure from normal density or activity of platelet of 5-HT(2A) receptors reflects severity of depression.