Ion Dysregulation in the Pathogenesis of Bipolar Illness

Background: Bipolar disorder is a severe, enigmatic condition that continues to be poorly understood and difficult to treat. True advances in the improvement of the prognosis of this condition will quickly follow insight into its pathogenesis. Ion dysregulatory abnormalities have remained among the most reproducible pathophysiologic alterations in this disease. Methods: A directed review of studies examining the pathophysiology of bipolar illness was performed. Results: Several lines of evidence support a central role of ion dysregulation in the pathogenesis of this disorder. Over 75% of all genes associated with bipolar illness are genes that control ion regulation. Measures of intracellular sodium and calcium reveal consistent abnormalities. Endogenous regulators of ion pumps appear to be dysregulated in bipolar patients. All effective agents share common mechanisms of reducing neuronal sodium influx and cellular excitability. And modeling these abnormalities in animals and in vitro produces manic-like, depressive-like behaviors, and cycling. Conclusion: A model is presented by which ion dysregulation can produce most of the characteristics of bipolar disorder.