Abstract
This report expands on previously presented evidence for a trait-dependent deficiency of erythrocyte sodium pump activity in bipolar affective disorder. Several parameters of erythrocyte NaK-ATPase activity in different affective states and the effects of lithium therapy were examined. In lithium-free bipolar affective disorder patients, the mean percent differences from the individual sex- and age-matched controls for erythrocyte sodium pump activity were: manic + hypomanic group, –21.5%, n = 16, p < 0.02; depressed group, –12.4%, n = 14, p < 0.02; euthymic group, –6.9%, n = 18, p < 0.10. Ouabain-sensitive potassium ion uptake was less than the controls in the manic group (-25.4%, n = 3, p < 0.02), and in the combined affectively ill group, manic + depressed (–23.4%, n = 7, p < 0.02). Cell ouabain binding was less than the controls in the manic group (–19.0%, n = 6, p < 0.05). NaK-ATPase activity in washed erythrocyte membranes (ghosts) was significantly lower than the controls in the manic group (–14.5 %, n = 4, p < 0.02), and the mean value for the whole group (manic + depressed + euthymic) was lower than the controls (–11.8%, n = 18, p < 0.05). Values for ouabain binding in ghosts from the bipolar subjects were not significantly different from the matched controls. For a group of bipolar subjects who were receiving lithium therapy, mean values for percent differences from matched controls for erythrocyte ouabain-sensitive sodium extrusion and potassium uptake, and for cell ouabain binding and ghost NaK-ATPase were all slightly positive but not significantly different from control values. Mean values for sodium pump activity for the group of bipolar subjects who were receiving lithium therapy (n = 55) were significantly higher than those for the group of lithium-free bipolar subjects (n = 53), p < 0.001). Sodium pump activity was deficient in affectively ill bipolar subjects before initiation of lithium therapy, and it increased significantly during lithium therapy (+29 %, n = 13, p < 0.01), to give values which were not significantly different from those of controls. In a group of nonbipolar subjects who received lithium therapy, sodium pump activity was not deficient before lithium therapy was initiated and was not significantly increased in this group during lithium therapy. These observations indicate that the trait-dependent deficiency of erythrocyte NaK-ATPase activity in bipolar disorder is most markedly manifest during affectively ill phases. The activity is restored to normal during lithium therapy.