PLATELET I-1-IMIDAZOLINE BINDING-SITES ARE ELEVATED IN DEPRESSION BUTNOT GENERALIZED ANXIETY DISORDER

Depressed patients have been reported to have a higher than normal den sity of platelet binding sites for H-3-clonidine, an alpha(2)-adrenoce ptor agonist. Paradoxically, other studies using H-3-alpha(2)-antagoni sts have found no differences from controls. Because H-3-clonidine int eracts with platelet alpha(2)-adrenoceptors to form G-protein complexe s, whereas H-3-alpha(2)-antagonists bind with uncoupled receptors, an elevation in G-protein coupling might explain this paradox. Another po ssibility is that depression might be associated with increased non-ad renergic I-1-imidazoline binding sites, which are also clonidine sensi tive. To distinguish these possibilities, we utilized p(125)I-clonidin e to measure density (B-max) and affinity (K-D) of platelet G-protein coupled alpha(2)-adrenoceptors as well as platelet I-1 binding sites, and compared diagnostic groups of major depressive disorder (MDD), gen eralized anxiety disorder (GAD) and healthy subjects. Specific inhibit ion of binding by norepinephrine (NE = 10 mu M) was used to selectivel y quantify alpha(2)-adrenoceptors, whereas inhibition by 10 mu M moxon idine (a > 100-fold selective I-1 ligand) quantified I-1 binding sites under a NE mask. I-1 sites were found to be markedly elevated by, on average, + 136% in MDD patients (p = .0007), whereas there was only a marginal increase in alpha(2)-adrenoceptor B-max values in MDD patient s (p = .08; GAD and healthy subjects did not differ). Treatment of MDD patients for 6-8 weeks with desipramine downregulated I-1 sites as we ll as alpha(2)-adrenoceptors. Positive correlations were also noted fo r both sites: (a) between B-max values and the severity of depression (using the Hamilton Depression Rating Scale); and (b) between end-of-t reatment plasma desipramine concentrations and the extent of downregul ation in B-max values when subject groups were pooled. None of the bin ding parameters was associated with plasma catecholamine concentration s. The results suggest that an increased density of platelet I-1 bindi ng sites may partially explain the utility of radiolabeled clonidine a s a potential biological marker for depressive illness, although an ad ditional increase in G-protein coupling cannot be excluded. Copyright (C) 1996 Elsevier Science Ltd.