조증에서 Lithium 치료효과와 적혈구 Lithium Efflux 와의 관계

Lithium Efflux and Clinical Response to Lithium Therapy in Manic Patients

In recent years many psychiatrists have been attracted by the promising reports about the RBC lithium efflux as a predictor of clinical response. The major impetus in this area comes from the report by Haas and his colleagues (1975) that the Li-Na counter flow system in human RBCs produces the uphill lithium efflu x, which means that the lithium ion is driven up its electrochemical potential by an oppositely directed sodiumion electrochem ical potential. Pandey and his colleagues (1977􀃂1979) reported that patients with manic depressive illness have higher lithium ratios (definedas intracellular lithium concentration/ extracellular lithium concentration) and lower lithium effluxes than normal controls presumably due to inherited Li-Na counter flow system defect. This study attempts to confirm the predictability of the clinical response to lithium with lithium e fflu x in RBCs. The subjects in this study were 15 manic patients and 5 normal controls. The manic patients w ere maintained on lithium carbonate 900 to 2, lOOmg per day for a minimum of 5 weeks. T he controls on lithium carbonate were on fixed doses of 900mg per day for 2 weeks. Blood was sampled 12 hours after last lithium intake. In vivo lithium concentration in plasma and RBC was measured by adoption of “repetitive thawing method” to obtain complete hemolysis of the RBCs. Uphill lithium efflux was measured from erythrocytes loaded with lithium to give an erythrocyte lithium concentration at a level of m Eq./L, follow ed by suspension in isotonic solution containing 135mM NaCl, 5mM KCI and 1 .5mMLiCl for 4 hours. Leak effusions were measured from m Eq./L. Li-loaded erythrocytes by suspension in solution containing NaCl 140m Eq ./L , and furosemide 10~3 M for 1 hour. The following results could be obtained Manic patients showed 3-fold interindividual variation of invivolithium ratio and control cases did 2-fold one. Inivo RBC lithium ratios were significantly higher in the manics than in the controls This result suggests that there is some defect of the lithium transport system in RBC membrane of manic patient. Among the manics, RBC lithium ratio was higher in early responders than in delayed responders. More over uphill lithium effluxes as well as downhill lithium effluxes were evidently lower in the early responders than in the delayed responders. There was no significant correlation between leak effusion and lithium ratio. From the fact that lithium ratio has a highly reverse correlation with uphill and downhill lithium effluxes, one can suggest that early responders have more severely defective Li-Na counterflow system than delayed responders. Consequently, RBC lithium efflux was proved to be valuable for predicting the response to lithium in mania.