Erythrocyte lithium efflux in bipolar patients and control subjects: the question of reproducibility

The reproducibility of in vitro erythrocyte lithium efflux and lithium efflux in the presence of selected membrane transport inhibitors (phloretin, ouabain, 4,4'-diisothiocyano-2,2'-disulphonic acid stilbene, and p-chloromercury-benzene sulphonate) was investigated in bipolar patients and age- and sex-matched control subjects. Efflux experiments were repeated three times in each patient-control pair within a period of 14 days. No differences were detected between patients and control subjects in any of the parameters measured. All components of lithium efflux showed wide day-to-day variation in the same subject in both patients and control subjects. Intersubject variability, however, was significantly greater than intrasubject variation. Since intraindividual variation of phloretin-inhibited lithium efflux was found to be considerable, and no real patient-control differences could be detected, the significance of this in vitro parameter in bipolar affective illness seems somewhat questionable and should be carefully reconsidered. The relevance of these findings to the putative cell membrane dysfunction in this disease is discussed.