MEMBRANE TRANSPORT PROCESSES IN AFFECTIVE ILLNESS

Abstract

Previous investigations have suggested that lithium transport, may be altered in erythrocytes (RBCs) from patients with bipolar affective disorder. The earliest studies measured the transmembrane distribution of lithium between RBCs and plasma during treatment with this agent, and the findings from different groups of investigators were contradictory. Subsequent studies showed that invivo measurements of transmembrane lithium distribution are subject to several sources of experimental variability. To overcome these methodological difficulties, a number of investigators have studied transmembrane lithium distribution invitro. Such in vitro investigations have provided some support for the idea that lithium transport by RBCs from bipolar patients may be altered as compared to control subjects. Such studies have also provided evidence of similar alterations in RBCs from the relatives of bipolar patients who themselves have a history of affective disorder. Only a limited number of studies have compared direct measurements of lithium efflux in various categories of subjects. These studies have generally found slightly lower mean lithium efflux rates in bipolar patients than in control subjects, although there is disagreement as to the statistical significance of this observation. Preliminary evidence from our laboratory suggests that simultaneous consideration of sodium influx in addition to lithium efflux substantially increases the significance of the difference between bipolar patients and control subjects. Our findings suggest that lithium and sodium transport by the Na+-Li+ countertransport system may be altered in a subgroup of patients with bipolar affective disorder. This chapter also briefly reviews the effects of lithium treatment on RBC membrane transport processes for lithium, sodium, and choline.