School of Medicine Publications and Presentations
Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder
Document Type
Article
Publication Date
2-1-2019
Abstract
Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium-responsive BD patients (Li-R) would show characteristic differences in chronotype and cellular circadian rhythms compared to lithium non-responders (Li-NR). Selecting patients from a prospective, multi-center, clinical trial of lithium monotherapy, we examined morning vs. evening preference (chronotype) as a dimension of circadian rhythm function in 193 Li-R and Li-NR BD patients. From a subset of 59 patient donors, we measured circadian rhythms in skin fibroblasts longitudinally over 5 days using a bioluminescent reporter (Per2-luc). We then estimated circadian rhythm parameters (amplitude, period, phase) and the pharmacological effects of lithium on rhythms in cells from Li-R and Li-NR donors. Compared to Li-NRs, Li-Rs showed a difference in chronotype, with higher levels of morningness. Evening chronotype was associated with increased mood symptoms at baseline, including depression, mania, and insomnia. Cells from Li-Rs were more likely to exhibit a short circadian period, a linear relationship between period and phase, and period shortening effects of lithium. Common genetic variation in the IP 3 signaling pathway may account for some of the individual differences in the effects of lithium on cellular rhythms. We conclude that circadian rhythms may influence response to lithium in maintenance treatment of BD.
Recommended Citation
McCarthy, M. J., Wei, H., Nievergelt, C. M., Stautland, A., Maihofer, A. X., Welsh, D. K., Shilling, P., Alda, M., Alliey-Rodriguez, N., Anand, A., Andreasson, O. A., Balaraman, Y., Berrettini, W. H., Bertram, H., Brennand, K. J., Calabrese, J. R., Calkin, C. V., Claasen, A., Conroy, C., Coryell, W. H., … Kelsoe, J. R. (2019). Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(3), 620–628. https://doi.org/10.1038/s41386-018-0273-8
First Page
620
Last Page
628
Publication Title
Neuropsychopharmacology
DOI
10.1038/s41386-018-0273-8
Academic Level
faculty
Mentor/PI Department
Neuroscience
Comments
© American College of Neuropsychopharmacology 2018