Manic depression etiology

The phosphatidylinositol pathway is completed by regeneration of the phospholipid from IP3 and DG. It is remarkable that IP3 is successively dephosphorylated to mositol. The last step of this sequence is inhibited by Li ions, which block phosphatidylinositol synthesis. Li salts are used to control the symptoms of manic-depressive illness, an affective mental disorder (see section 3.5.4), and it is thus tempting to implicate the last reaction of the PI pathway in the etiology of this disorder. 

There may be abnormalities in eiythrocyte membrane transport properties in patients with bipolar affective disorders, though the interpretation is confounded by the uncertainty with regard to the contribution of hypertension in patients who are coincidentally hypertensive and manic depressive. The administration of lithium also may cause adaptive change (93,117,135-137). This results in an increase in erythrocyte lithium concentrations after prolonged lithium therapy, which could be mediated either by increased flux into the cell or via reduction in efflux rate. An increased content of ankyrins, red cell membrane proteins affecting cytoskeletal structure and functions, has been found in some patients with bipolar affective disorder (138) and this raises further the role of erythrocyte membrane defects in the etiology of the disease. 

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