INCREASED SENSITIVITY OF THE INOSITOL-PHOSPHOLIPID SYSTEM IN NEUTROPHILS FROM PATIENTS WITH ACUTE MAJOR DEPRESSIVE EPISODES

Evidence from in vitro and in vivo studies suggests that the therapeut ic and prophylactic effects of lithium in recurrent affective disorder s are due to an attenuation of the inositol-phospholipid (IPL) second messenger system. An increased sensitivity of this signal transduction system might therefore constitute a risk factor for affective illness . The extent of the agonist-induced release of intracellular Ca2+ (Ca2 + response) can be used as an indicator of the sensitivity of the IPL system. Using this paradigm, we have measured the agonist-induced Ca2 response in neutrophils of 17 unmedicated patients who were experienc ing an acute major depressive episode. The neutrophils were stimulated by the chemotactic peptide formylmethionylleucylphenylalanine, which activates the IPL system in the cells. The sensitivity of the IPL syst em in these patients was significantly greater (dose-response curve sh ifted to the left) compared with its sensitivity in healthy age- and s ex-matched control subjects. The results indicate that acute episodes of major depression are associated with an increased sensitivity of th e IPL system.