Possible role of endogenous ouabain-like compounds in the pathophysiology of bipolar Illness

A large number of studies have documented a mood-state-related decrease in blood cell sodium, potassium-activated adenosine triphosphatase (Na, K-ATPase) activity in acutely ill bipolar patients. While it has been proposed that this enzymatic change may be central to the pathophysiology of bipolar illness, its genesis has remained obscure. Recent advances in the isolation and characterization of endogenously produced ouabain- or digoxin-like compounds suggest a possible mechanism by which these mood-state-related changes can come about. We herein propose that the hypothalamic-pituitary-adrenal dysregulation frequently documented in major mood disorders may underlie a pathological increase in the production of endogenous ouabain-like compounds which excessively suppresses Na, K-ATPase activity and results in pathological mood and energy alteration.