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About the Authors:
Michael J. McCarthy
* E-mail: [email protected]
Affiliations Veterans Affairs San Diego Healthcare System, San Diego, California, United Sates of America, Department of Psychiatry, University of California San Diego, La Jolla, California, United States of America, Center for Chronobiology, University of California San Diego, La Jolla, California, United States of America
Caroline M. Nievergelt
Affiliations Department of Psychiatry, University of California San Diego, La Jolla, California, United States of America, Center for Chronobiology, University of California San Diego, La Jolla, California, United States of America
John R. Kelsoe
Affiliations Veterans Affairs San Diego Healthcare System, San Diego, California, United Sates of America, Department of Psychiatry, University of California San Diego, La Jolla, California, United States of America, Center for Chronobiology, University of California San Diego, La Jolla, California, United States of America
David K. Welsh
Affiliations Veterans Affairs San Diego Healthcare System, San Diego, California, United Sates of America, Department of Psychiatry, University of California San Diego, La Jolla, California, United States of America, Center for Chronobiology, University of California San Diego, La Jolla, California, United States of America
Introduction
Bipolar disorder (BD) is a serious and life-threatening mental illness that affects 1–2% of the population. Twin and family studies have found that the heritability of BD is up to 0.85, suggesting a strong genetic liability [1]. But despite considerable effort, the precise genetic factors that predispose to BD remain unknown. Based upon clinical observations that patients with BD often exhibit evening chronotype, disturbances in periodic daily activities (e.g. decreased need for sleep, insomnia or hypersomnia, disturbed appetite, and disrupted daily activity patterns), and that mood episodes are affected by light and follow seasonal patterns, a circadian rhythm hypothesis of BD and depression has been developed [2]. This hypothesis has been supported by the development of a mouse model of BD in which a mutation in Clock, a core component of the cellular circadian clock, causes lithium-sensitive, mania-like behavioral abnormalities [3]–[4]. Moreover, the mood-stabilizing drug lithium, a mainstay of treatment for BD, also alters clock gene expression [5], and delays circadian rhythms in rodents, monkeys, and humans [6]–[9]. Glycogen synthase kinase 3β (GSK3β) is inhibited by lithium [10], and has been implicated in both lithium's effect on circadian rhythms [11], [12], and...