High Affinity Imipramine Binding and Serotonin Uptake in Human Platelets as a Peripheral Biological Marker in Neuropsychiatric Disorders

Abstract

High affinity binding sites for [3H]imipramine have been demonstrated and characterized in rat and human brain1,2 and platelets.3,4 These binding sites are functionally related to the presynaptic uptake or transport site for serotonin and are probably involved in the well known inhibition effect of tricyclic antidepressants on biogenic amine uptake.5 A significant decrease in the density of [3H]imipramine binding sites in platelets of severely depressed patients compared to age- and sex- matched controls was reported by Briley et al.6 and Paul et al.7 These results were replicated by several investigators (reviewed in refs. 8,9), although other studies have not confirmed this decrease.10 Chronic imipramine treatment induced parallel decreases in [3H]imipramine binding and serotonin uptake in cat platelets and brain, suggesting that these sites are functionally related.11 It seems that the decrease in the number of imipramine binding sites in platelets of major depressed patients reflects parallel changes in human brain, as low values of Bmax for [3H]imipramine binding were observed in frontal cortex and hypothalamus of suicides.12,13 The involvement of the serotonergic system in the pathophysiology of depression is further supported by the low serotonin uptake to platelets of patients with major depression14 and reduced 5-hydroxyindoleacetic acid (5-HIAA) levels in the cerebrospinal fluid (CSF) of affective patients.15 It was reported that platelet [3H]imipramine binding might serve as a possible predictor of response to antidepressant treatment16; it was also reported to be correlated with the severity of depression17 and to distinguish among subtypes of depression.18.