Role of intracellular calcium signaling in the pathophysiology and pharmacotherapy of bipolar disorder: current status

Evidence implicating disturbances of intracellular Ca2+ homeostasis has continued to accumulate, with a recent burst of new observations obtained using cultured cell lines from patients with bipolar disorder (BD) suggesting that disturbances occur in receptor-activated and store-operated calcium entry. The potential confounding effects of state of illness and medications on results obtained with various surrogate cellular models is reviewed, and the extent to which findings may reflect trait changes is considered. The role of ER and mitochondria in maintaining intracellular Ca2+ homeostasis and in protecting against induction of apoptosis is now better understood. Disrupted Ca2+ dynamics found in cell lines from BD patients point to disturbances in these homeostatic control modules in the pathophysiology of a subtype of BD. This notion is further supported by convergence of observations that, on the one hand, show therapeutic concentrations of lithium modifies intracellular Ca2+ dynamics in non-human and human cell lines of different ontogeny, and on the other hand, demonstrate that this mood stabilizer modulates anti-apoptotic protein expression that counteracts mitochondrial/ER stress-induced impairment in Ca2+ homeostasis. (C) 2004 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved.