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Patients with bipolar disorder show abnormal concentrations of the cardenolide steroid ouabain-like immunoreactive factor (OLF), which is thought to regulate sodium ion pump activity, researchers report.
Study author Rif El-Mallakh (University of Louisville School of Medicine, Kentucky, USA) and colleagues note that one of the most accepted pathophysiologic abnormalities in bipolar disorder is the dysregulation of ion homeostasis.
Bipolar disorder patients in a manic phase exhibit an increase of intracellular sodium and calcium concentrations, and a reduction of membrane sodium pump expression and activity, the researchers note in the journal Psychiatry Research.
One factor behind this dysregulation may be the secretion of steroid cardenolides from the adrenal gland and hypothalamus, which are thought to regulate ion pumps. Secretion of cardenolides has been shown to increase in certain situations in non-psychiatric patients, such as during exercise.
In the current study, 14 euthymic patients with bipolar disorder and 10 mentally healthy controls performed exercise to exhaustion while plasma concentrations of endogenous cardenolides were measured at baseline, 60 min (or exercise termination if less than 60 min), peak exercise, and post recovery.
Four endogenous cardenolides were quantified: OLF, digoxin-like factor (DLF), dihydro-digoxin-like factor (dihydroDLF), and dihydro-ouabain-like factor (dihydroOLF).
Of these, only OLF was lower in patients than controls at the measurement points: baseline (0.01 ng/ml vs 0.072 ng/ml); 60 min (0.02 ng/ml vs 0.075 ng/ml); and at peak exercise (0.02 ng/ml vs 0.131 ng/ml).
El-Mallakh and colleagues suggest that bipolar disorder patients are less capable than mentally healthy controls at increasing OLF levels “under conditions of increased need.”
They note that unpublished preliminary studies by their team have demonstrated that OLF production may increase in normal sleep-deprived mice.
The researchers conclude: “If sleep deprivation is associated with a natural increase of OLF levels, bipolar subjects may be unable to respond appropriately and, consequently, experience a state of relative OLF deficiency.
“This would lead to a relative decrement in sodium pump activity, an increase of intracellular sodium with consequent increase of intracellular calcium and activation of second messengers, and induce symptoms of mania and depression.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
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