Circadian rhythm disorders in manic-depressives.

Seven circular manic-depressives were studied through complete of cycles of mania and depression. In five subjects, there was evidence that a circadian rhythm free-ran fast (p less than 0.005 and p less than 0.002 in two of the subjects), and in five subjects, there was evidence that lithium slowed a circadian rhythm. The palliative benefit of lithium may derive from slowing or delaying an overfast circadian clock to prevent desynchronization. Two subjects whose circadian clocks seemed too slow were lithium nonresponders (p less than 0.05). As circadian clock frequency may be transmitted on an X-chromosome gene and may increase with age, a circadian etiology is consistent with the genetics and age distribution of manic-depressive illness. Affective disturbances could be evolutionary remnants of the photo-periodic seasonal responses in animals.