Platelet imidazoline receptors as state marker of depressive symptomatology

ObjectivePrevious studies have shown that imidazoline receptors (IR-1) are increased in platelets and frontal cortex of depressed patients, and this up-regulation is normalized (down-regulated) after antidepressant drug treatments. It has been hypothesized that IR-1 up-regulation during the depressive episode may be a state marker for depressive symptomatology. The goal of the present study was to address the state versus trait question.MethodTwelve healthy subjects (six males and six females) met stringent inclusion and exclusion criteria for physical and mental health. They received desipramine for 6 weeks in order to simulate the length of time and dosing used previously to obtain an IR-1 down-regulation and a therapeutic response in depressed patients. Outcome and safety measures included clinical, psychological, and cardiovascular assessments obtained throughout the study. Plasma concentrations of desipramine were measured throughout the 6 weeks of treatment and again after 2 weeks following tapered discontinuation of desipramine. Platelet receptors were assessed by Western blotting and radioligand binding assays.ResultsHealthy subjects taking desipramine experienced mild dysphoric effects but there were no adverse events. The binding of 8 nM p-[125I]clonidine to IR-1 and α2-adrenoceptors in healthy subjects did not change during desipramine treatment. The immunodensity of the 33 kDa band associated with IR-1 gradually increased to a maximum, by week-6, of 26% higher than baseline (p < 0.01 compared to baseline). Two weeks after desipramine discontinuation, there was a decline in α2-adrenoceptor binding and 33 kDa band’s immunodensity (p = 0.04).ConclusionsThe findings support the hypothesis that platelet IR-1 binding sites are a marker of mood state rather than of antidepressant-induced pharmacological regulation. By comparison, platelet α2-adrenoceptors appear to be regulated by desipramine as a pharmacological effect independent of mood state.