Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder

Monica Federoff; Michael J. McCarthy; Amit Anand; Wade H. Berrettini; Holli Bertram; Abesh Bhattacharjee; Cynthia V. Calkin; Carla Conroy; William H Coryell; Nicole D'Arcangelo; Anna DeModena; Carrie Fisher; Scott Feeder; Nicole Frazier; Mark A. Frye; Keming Gao; Julie Garnham; Elliot S. Gershon; Ney Alliey-Rodriguez; Kara Glazer; Fernando Goes; Toyomi Karberg; Gloria Harrington; Petter Jakobsen; Masoud Kamali; Marisa Kelly; Susan G. Leckband; Falk Lohoff; Adam X. Maihofer; Melvin G McInnis; Francis Mondimore; Gunnar Morken; John I. Nurnberger; Ketil J. Oedegaard; Megan Ritchey; Kelly Ryan; Martha Schinagle; Helle Schoeyen; Candice Schwebel; Martha Shaw; Paul D. Shilling; Claire Slaney; Andrea Stautland; Bruce Tarwater; Joseph R. Calabrese; Martin Alda; Caroline M. Nievergelt; Peter P. Zandi; John R. Kelsoe

doi:10.1111/bdi.13162

Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder

Monica Federoff, Michael J. McCarthy, Amit Anand, Wade H. Berrettini, Holli Bertram, Abesh Bhattacharjee, Cynthia V. Calkin, Carla Conroy, William H Coryell, Nicole D'Arcangelo, Anna DeModena, Carrie Fisher, Scott Feeder, Nicole Frazier, Mark A. Frye, Keming Gao, Julie Garnham, Elliot S. Gershon, Ney Alliey-Rodriguez, Kara GlazerFernando Goes, Toyomi Karberg, Gloria Harrington, Petter Jakobsen, Masoud Kamali, Marisa Kelly, Susan G. Leckband, Falk Lohoff, Adam X. Maihofer, Melvin G McInnis, Francis Mondimore, Gunnar Morken, John I. Nurnberger, Ketil J. Oedegaard, Megan Ritchey, Kelly Ryan, Martha Schinagle, Helle Schoeyen, Candice Schwebel, Martha Shaw, Paul D. Shilling, Claire Slaney, Andrea Stautland, Bruce Tarwater, Joseph R. Calabrese, Martin Alda, Caroline M. Nievergelt, Peter P. Zandi, John R. Kelsoe

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Bipolar disorder (BD) is characterized by episodes of depression and mania and disrupted circadian rhythms. Lithium is an effective therapy for BD, but only 30%–40% of patients are fully responsive. Preclinical models show that lithium alters circadian rhythms. However, it is unknown if the circadian rhythm effects of lithium are essential to its therapeutic properties. 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.

Original language	English (US)
Pages (from-to)	521-529
Number of pages	9
Journal	Bipolar Disorders
Volume	24
Issue number	5
DOIs	https://doi.org/10.1111/bdi.13162
State	Published - Aug 2022

Keywords

bipolar disorder
chronotype
circadian rhythm
lithium
sleep

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

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10.1111/bdi.13162

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Federoff, M., McCarthy, M. J., Anand, A., Berrettini, W. H., Bertram, H., Bhattacharjee, A., Calkin, C. V., Conroy, C., Coryell, WH., D'Arcangelo, N., DeModena, A., Fisher, C., Feeder, S., Frazier, N., Frye, M. A., Gao, K., Garnham, J., Gershon, E. S., Alliey-Rodriguez, N., ... Kelsoe, J. R. (2022). Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder. Bipolar Disorders, 24(5), 521-529. https://doi.org/10.1111/bdi.13162

Federoff, M, McCarthy, MJ, Anand, A, Berrettini, WH, Bertram, H, Bhattacharjee, A, Calkin, CV, Conroy, C, Coryell, WH, D'Arcangelo, N, DeModena, A, Fisher, C, Feeder, S, Frazier, N, Frye, MA, Gao, K, Garnham, J, Gershon, ES, Alliey-Rodriguez, N, Glazer, K, Goes, F, Karberg, T, Harrington, G, Jakobsen, P, Kamali, M, Kelly, M, Leckband, SG, Lohoff, F, Maihofer, AX, McInnis, MG, Mondimore, F, Morken, G, Nurnberger, JI, Oedegaard, KJ, Ritchey, M, Ryan, K, Schinagle, M, Schoeyen, H, Schwebel, C, Shaw, M, Shilling, PD, Slaney, C, Stautland, A, Tarwater, B, Calabrese, JR, Alda, M, Nievergelt, CM, Zandi, PP & Kelsoe, JR 2022, 'Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder', Bipolar Disorders, vol. 24, no. 5, pp. 521-529. https://doi.org/10.1111/bdi.13162

@article{91c88713bb64423c967a81f46b11ecf8,

title = "Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder",

abstract = "Background: Bipolar disorder (BD) is characterized by episodes of depression and mania and disrupted circadian rhythms. Lithium is an effective therapy for BD, but only 30%–40% of patients are fully responsive. Preclinical models show that lithium alters circadian rhythms. However, it is unknown if the circadian rhythm effects of lithium are essential to its therapeutic properties. 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.",

keywords = "bipolar disorder, chronotype, circadian rhythm, lithium, sleep",

author = "Monica Federoff and McCarthy, {Michael J.} and Amit Anand and Berrettini, {Wade H.} and Holli Bertram and Abesh Bhattacharjee and Calkin, {Cynthia V.} and Carla Conroy and William H Coryell and Nicole D'Arcangelo and Anna DeModena and Carrie Fisher and Scott Feeder and Nicole Frazier and Frye, {Mark A.} and Keming Gao and Julie Garnham and Gershon, {Elliot S.} and Ney Alliey-Rodriguez and Kara Glazer and Fernando Goes and Toyomi Karberg and Gloria Harrington and Petter Jakobsen and Masoud Kamali and Marisa Kelly and Leckband, {Susan G.} and Falk Lohoff and Maihofer, {Adam X.} and Melvin G McInnis and Francis Mondimore and Gunnar Morken and Nurnberger, {John I.} and Oedegaard, {Ketil J.} and Megan Ritchey and Kelly Ryan and Martha Schinagle and Helle Schoeyen and Candice Schwebel and Martha Shaw and Shilling, {Paul D.} and Claire Slaney and Andrea Stautland and Bruce Tarwater and Calabrese, {Joseph R.} and Martin Alda and Nievergelt, {Caroline M.} and Zandi, {Peter P.} and Kelsoe, {John R.}",

note = "Publisher Copyright: {\textcopyright} 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",

year = "2022",

month = aug,

doi = "10.1111/bdi.13162",

language = "English (US)",

volume = "24",

pages = "521--529",

journal = "Bipolar Disorders",

issn = "1398-5647",

publisher = "Blackwell Munksgaard",

number = "5",

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TY - JOUR

T1 - Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder

AU - Federoff, Monica

AU - McCarthy, Michael J.

AU - Anand, Amit

AU - Berrettini, Wade H.

AU - Bertram, Holli

AU - Bhattacharjee, Abesh

AU - Calkin, Cynthia V.

AU - Conroy, Carla

AU - Coryell, William H

AU - D'Arcangelo, Nicole

AU - DeModena, Anna

AU - Fisher, Carrie

AU - Feeder, Scott

AU - Frazier, Nicole

AU - Frye, Mark A.

AU - Gao, Keming

AU - Garnham, Julie

AU - Gershon, Elliot S.

AU - Alliey-Rodriguez, Ney

AU - Glazer, Kara

AU - Goes, Fernando

AU - Karberg, Toyomi

AU - Harrington, Gloria

AU - Jakobsen, Petter

AU - Kamali, Masoud

AU - Kelly, Marisa

AU - Leckband, Susan G.

AU - Lohoff, Falk

AU - Maihofer, Adam X.

AU - McInnis, Melvin G

AU - Mondimore, Francis

AU - Morken, Gunnar

AU - Nurnberger, John I.

AU - Oedegaard, Ketil J.

AU - Ritchey, Megan

AU - Ryan, Kelly

AU - Schinagle, Martha

AU - Schoeyen, Helle

AU - Schwebel, Candice

AU - Shaw, Martha

AU - Shilling, Paul D.

AU - Slaney, Claire

AU - Stautland, Andrea

AU - Tarwater, Bruce

AU - Calabrese, Joseph R.

AU - Alda, Martin

AU - Nievergelt, Caroline M.

AU - Zandi, Peter P.

AU - Kelsoe, John R.

PY - 2022/8

Y1 - 2022/8

N2 - Background: Bipolar disorder (BD) is characterized by episodes of depression and mania and disrupted circadian rhythms. Lithium is an effective therapy for BD, but only 30%–40% of patients are fully responsive. Preclinical models show that lithium alters circadian rhythms. However, it is unknown if the circadian rhythm effects of lithium are essential to its therapeutic properties. 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.

AB - Background: Bipolar disorder (BD) is characterized by episodes of depression and mania and disrupted circadian rhythms. Lithium is an effective therapy for BD, but only 30%–40% of patients are fully responsive. Preclinical models show that lithium alters circadian rhythms. However, it is unknown if the circadian rhythm effects of lithium are essential to its therapeutic properties. 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.

KW - bipolar disorder

KW - chronotype

KW - circadian rhythm

KW - lithium

KW - sleep

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UR - http://www.scopus.com/inward/citedby.url?scp=85120561941&partnerID=8YFLogxK

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DO - 10.1111/bdi.13162

M3 - Article

C2 - 34825444

AN - SCOPUS:85120561941

SN - 1398-5647

VL - 24

SP - 521

EP - 529

JO - Bipolar Disorders

JF - Bipolar Disorders

IS - 5

ER -

Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder

Abstract

Keywords

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