Calcium Channel May Be Responsible for Circadian Rhythm Abnormalities in Bipolar Disorder
Genetic variation in L-type calcium channel genes have been linked to bipolar disorder. Since calcium plays an important role in circadian rhythms, abnormalities in the calcium channel in bipolar disorder could explain some of the circadian rhythm disturbances patients with bipolar disorder exhibit. New research by Michael McCarthy and colleagues shows that calcium channels in general, and the gene CACNA1C in particular, affect signaling pathways that regulate circadian rhythms in both human and animal cells. The researchers also found that calcium channels affected how lithium changes circadian rhythms, suggesting a mechanism by which the treatment may work. They suggest that drugs that affect the L-type calcium channel may be promising treatments for bipolar disorder.
Editor’s Note: The L-type calcium channel blocker nimodipine has had antidepressant, antimanic, and anticycling effects in some patients with bipolar disorder in small studies both by Peggy Pazzaglia and colleagues (including this author Robert Post) and a larger randomized study by Haroon R. Chaudhry.
The clinical effects of nimodipine results thus align with studies linking the CACNA1C gene to bipolar illness and its early onset, increased expression of the gene in the brain of bipolar patients in autopsy studies, increased levels of calcium in white cells of bipolar patients, and a variety of other neurobiological phenomena observed in normal controls carrying the risk gene.
The new link found between CACNA1C and circadian rhythms further links the L-type calcium channel abnormality and bipolar disorder, as well as the therapeutic effects of the L-type calcium channel blocker nimodipine. This drug deserves further study, especially in those with the genetic variation in CACNA1C that has been linked to bipolar disorder.
