Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder.
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Federoff Monica, McCarthy Michael J, Anand Amit, Berrettini Wade H, Bertram Holli, Bhattacharjee Abesh, Calkin Cynthia V, Conroy Carla, Coryell William H, D'Arcangelo Nicole, DeModena Anna, Fisher Carrie, Feeder Scott, Frazier Nicole, Frye Mark A, Gao Keming, Garnham Julie, Gershon Elliot S, Alliey-Rodriguez Ney, Glazer Kara, Goes Fernando, Karberg Toyomi, Harrington Gloria, Jakobsen Petter, Kamali Masoud, Kelly Marisa, Leckband Susan G, Lohoff Falk, Maihofer Adam X, McInnis Melvin G, Mondimore Francis, Morken Gunnar, Nurnberger John I, Oedegaard Ketil J, Ritchey Megan, Ryan Kelly, Schinagle Martha, Schoeyen Helle, Schwebel Candice, Shaw Martha, Shilling Paul D, Slaney Claire, Stautland Andrea, Tarwater Bruce, Calabrese Joseph R, Alda Martin, Nievergelt Caroline M, Zandi Peter P, Kelsoe John R
Аннотация
METHODS: In secondary analyses of a multi-center, prospective, trial of lithium for BD, we examined the relationship between circadian rhythms and therapeutic response to lithium. Using standardized instruments, we measured morningness, diurnal changes in mood, sleep, and energy (circadian rhythm disturbances) in a cross-sectional study of 386 BD subjects with varying lithium exposure histories. Next, we tracked symptoms of depression and mania prospectively over 12 weeks in a subset of 88 BD patients initiating treatment with lithium. Total, circadian, and affective mood symptoms were scored separately and analyzed.
RESULTS: Subjects with no prior lithium exposure had the most circadian disruption, while patients stable on lithium monotherapy had the least. Patients who were stable on lithium with another drug or unstable on lithium showed intermediate levels of disruption. Treatment with lithium for 12 weeks yielded significant reductions in total and affective depression symptoms. Lithium responders (Li-Rs) showed improvement in circadian symptoms of depression, but non-responders did not. There was no difference between Li-Rs and nonresponders in affective, circadian, or total symptoms of mania.
CONCLUSIONS: Exposure to lithium is associated with reduced circadian disruption. Lithium response at 12 weeks was selectively associated with the reduction of circadian depressive symptoms. We conclude that stabilization of circadian rhythms may be an important feature of lithium's therapeutic effects.
CLINICAL TRIALS REGISTRY: NCT0127253.