Intracellular Calcium Ion Signaling in Bipolar Mood Disorders: New Data and Directions

Steven L Dubovsky


Bipolar mood disorders comprise a heterogeneous group of conditions all of which are characterized by alternations or mixtures of elevated and depressed mood and physiologic arousal. Traditional hypotheses of the neurobiology of bipolar disorder that have invoked increases or decreases in neurotransmitter and receptor activity do not explain the existence at the same time of contradictory emotional states or comorbidity with medical disorders such as hypertension, coronary heart disease and migraine headaches. Unitary changes in neurotransmission also do not elucidate the reason why antidepressant treatments can destabilize the mood disorder, whereas a single medication (mood stabilizer) can ameliorate both poles of this condition. In contrast, changes in basic cellular functions such as the calcium (Ca2+) second messenger system can drive multiple neuronal systems in different directions depending on the sensitivity of a particular system to activation or inhibition by increased concentrations of the second messenger. This article summarizes evidence of elevated baseline and stimulated intracellular calcium ion concentration ([Ca2+]i) in peripheral cells and neuronal cultures in mania and bipolar depression and presents new data on induction of increased lymphocyte [Ca2+]I in a primate separation model. Data are presented supporting calcium antagonist actions of some mood stabilizers and mood stabilizing actions of some calcium channel blockers. This research points to new directions in understanding mood disorders and devising more specific treatments.


bipolar disorder, calcium ion, second messenger, neurobiology, platelet, calcium channel blockers, mood stabilizers

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