Relation between Erythrocyte and Plasma Lithium Concentrations as an Index in Psychiatric Disease

Abstract

In longitudinal and transverse studies, lithium was measured in plasma, serum and red blood cells (erythrocytes) of healthy male and female subjects as well as in patients of both sexes suffering from manic-depressive disease or schizophrenia. The results confirm that lithium in erythrocytes is lower than in plasma in all groups. The lithium concentration gradient between plasma and erythrocytes is not caused by a slow rate of diffusion through the erythrocyte membrane. The new result of the present study is the importance of sex, disease and age on the erythrocyte/plasma lithium ratio, which is significantly higher in female subjects with manic-depressive disease. This difference persists even during long-term lithium therapy. Older female schizophrenics also have a higher ratio of erythrocyte to plasma lithium than males of the same age. The findings emphasize the importance of endocrine investigation in mental disease and support the view that plasma lithium in humans does not always reflect the intracellular levels. The erythrocyte plasma ratio may also be of value in revealing diagnostic subgroups within the classical psychiatric framework.

Erythrocyte Lithium and the Erythrocyte: Plasma Lithium Ratio as Indicators of Mood Changes: Preliminary Report

“…2 ' 4 ' 8 The therapeutic minimum RBC:plasma lithium ratio has been proposed to be at least 0.22, but the RBC:plasma lithium ratio requisite for adequate response to lithium therapy is uncertain. 3 …”

“….31 (5) .35(4) .23 (5) .40 (5) .50 (5) .37(4) .31 (5) .37 (5) .31 (5) .55 (5) .40 (5) .83 (5) .32 (4) .20 (3) .54 (5) RBC: PLASMA LITHIUM RATIO…”

“…Lyttkens also noted a tendency for female manic-depressive patients to show higher RBC: plasma lithium ratios. 3 Three patients were diagnosed as having bipolar illness with possible schizophrenia. We recognize that these patients may have purely bipolar disease and therefore, are presently reducing antipsychotic medications which had been initiated by their previous physicians.…”

Comments on “Perspectives, attitude, and practice of lithium prescription among psychiatrists in India”

“…The authors stated that “the majority of psychiatrists who completed the survey were of the opinion that lithium dose titrations should be done both in the acute phase and maintenance phase on a dose-dependent basis rather than the blood level-dependent basis.” One of the most important known evidence is that plasma lithium in humans does not always reflect the intracellular levels. [ 4 ] This could explain the possible scientific explanation as to why majority of psychiatrists in the survey opted for a dose-dependent titration rather than the blood level-dependent titration of Lithium to improve the symptoms.…”

Red Blood Cell Plasma Li Ratio Variability in Affective Patients

“…Several reports about the usefulness of the Li ratio as an index of prediction suggested that the Li ratio, which might or might not be related to the responder/nonresponder dichotomy, could be a marker for the biological heterogeneity that may underlie clinical subtypes of the disease [Litkens et al, 1973[Litkens et al, , 1976Mendlewicz et al, 1973;Morabito et al, 1982]. Hypotheses about different distributions of the Li ratio according to polarity of dis ease [Ribakowski et al, 1978;Knorring et al, 1976;Elizur et al, 1982;Albrecht and Miilier-Oerlinghausen, 1976;Andrews and Chiu, 1978] and to sex of probands [Litkens et al, 1973;Greil et al, 1979;Deniker et al.…”