Lithium in the living organism. Is an integrated hypothesis feasible?

1. The effects of lithium on electrolyte metabolism can be demonstrated in man in acute as well as in long-term lithium treatment. No other lithium effects have been reproducible to a similar extent. 2. It seems feasible to integrate these lithium effects with effects on biogenic amines to form an integral hypothesis for lithium action in manic-melancholic man. 3. The results are consistent with one of the following two hypotheses: a) that lithium acts by membrane stabilization and/or b) that lithium acts by interplay with magnesium on one or more enzymes. 4. The above findings and hypotheses direct our attention to membrane dysfunction as the basic defect in manic-melancholic states. This may find support in our preliminary findings of special HL-A profiles in unipolar and bipolar manic-melancholic patients. 5. A four-type-pump-defect model to account for the various clinical types of affective disorders is proposed.