The association between lithium use and neurocognitive performance in patients with bipolar disorder

Katherine E. Burdick; Caitlin E. Millett; Manuela Russo; Martin Alda; Ney Alliey-Rodriguez; Amit Anand; Yokesh Balaraman; Wade Berrettini; Holli Bertram; Joseph R. Calabrese; Cynthia Calkin; Carla Conroy; William Coryell; Anna DeModena; Scott Feeder; Carrie Fisher; Nicole Frazier; Mark Frye; Keming Gao; Julie Garnham; Elliot S. Gershon; Kara Glazer; Fernando S. Goes; Toyomi Goto; Gloria J. Harrington; Petter Jakobsen; Masoud Kamali; Marisa Kelly; Susan Leckband; Else Marie Løberg; Falk W. Lohoff; Adam X. Maihofer; Michael J. McCarthy; Melvin McInnis; Gunnar Morken; Caroline M. Nievergelt; John Nurnberger; Ketil J. Oedegaard; Abigail Ortiz; Megan Ritchey; Kelly Ryan; Martha Schinagle; Candice Schwebel; Martha Shaw; Paul Shilling; Claire Slaney; Emma Stapp; Bruce Tarwater; Peter Zandi; John R. Kelsoe

doi:10.1038/s41386-020-0683-2

The association between lithium use and neurocognitive performance in patients with bipolar disorder

Katherine E. Burdick, Caitlin E. Millett, Manuela Russo, Martin Alda, Ney Alliey-Rodriguez, Amit Anand, Yokesh Balaraman, Wade Berrettini, Holli Bertram, Joseph R. Calabrese, Cynthia Calkin, Carla Conroy, William Coryell, Anna DeModena, Scott Feeder, Carrie Fisher, Nicole Frazier, Mark Frye, Keming Gao, Julie GarnhamElliot S. Gershon, Kara Glazer, Fernando S. Goes, Toyomi Goto, Gloria J. Harrington, Petter Jakobsen, Masoud Kamali, Marisa Kelly, Susan Leckband, Else Marie Løberg, Falk W. Lohoff, Adam X. Maihofer, Michael J. McCarthy, Melvin McInnis, Gunnar Morken, Caroline M. Nievergelt, John Nurnberger, Ketil J. Oedegaard, Abigail Ortiz, Megan Ritchey, Kelly Ryan, Martha Schinagle, Candice Schwebel, Martha Shaw, Paul Shilling, Claire Slaney, Emma Stapp, Bruce Tarwater, Peter Zandi, John R. Kelsoe

Medicine

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

35 Citations (Scopus)

Abstract

Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1–5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1–5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically.

Original language	English
Pages (from-to)	1743-1749
Number of pages	7
Journal	Neuropsychopharmacology
Volume	45
Issue number	10
DOIs	https://doi.org/10.1038/s41386-020-0683-2
Publication status	Published - Sept 1 2020

Bibliographical note

Funding Information:
This work was supported by the US National Institutes of Mental Health and General Medical Sciences (MH92758 to JRK; MH100125 to KEB). KEB has served as an advisory board member to Dainippon Sumitomo Pharmaceutical Neuralstem, and Takeda- Lundbeck. JN has received funding as an investigator from Assurex and from Janssen. JRK has received funds from Pathway Genomics as an investigator. All other authors have nothing to disclose.

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.

ASJC Scopus Subject Areas

Pharmacology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41386-020-0683-2

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Burdick, K. E., Millett, C. E., Russo, M., Alda, M., Alliey-Rodriguez, N., Anand, A., Balaraman, Y., Berrettini, W., Bertram, H., Calabrese, J. R., Calkin, C., Conroy, C., Coryell, W., DeModena, A., Feeder, S., Fisher, C., Frazier, N., Frye, M., Gao, K., ... Kelsoe, J. R. (2020). The association between lithium use and neurocognitive performance in patients with bipolar disorder. Neuropsychopharmacology, 45(10), 1743-1749. https://doi.org/10.1038/s41386-020-0683-2

Burdick, KE, Millett, CE, Russo, M, Alda, M, Alliey-Rodriguez, N, Anand, A, Balaraman, Y, Berrettini, W, Bertram, H, Calabrese, JR, Calkin, C, Conroy, C, Coryell, W, DeModena, A, Feeder, S, Fisher, C, Frazier, N, Frye, M, Gao, K, Garnham, J, Gershon, ES, Glazer, K, Goes, FS, Goto, T, Harrington, GJ, Jakobsen, P, Kamali, M, Kelly, M, Leckband, S, Løberg, EM, Lohoff, FW, Maihofer, AX, McCarthy, MJ, McInnis, M, Morken, G, Nievergelt, CM, Nurnberger, J, Oedegaard, KJ, Ortiz, A, Ritchey, M, Ryan, K, Schinagle, M, Schwebel, C, Shaw, M, Shilling, P, Slaney, C, Stapp, E, Tarwater, B, Zandi, P & Kelsoe, JR 2020, 'The association between lithium use and neurocognitive performance in patients with bipolar disorder', Neuropsychopharmacology, vol. 45, no. 10, pp. 1743-1749. https://doi.org/10.1038/s41386-020-0683-2

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abstract = "Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1–5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1–5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically.",

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note = "Funding Information: This work was supported by the US National Institutes of Mental Health and General Medical Sciences (MH92758 to JRK; MH100125 to KEB). KEB has served as an advisory board member to Dainippon Sumitomo Pharmaceutical Neuralstem, and Takeda- Lundbeck. JN has received funding as an investigator from Assurex and from Janssen. JRK has received funds from Pathway Genomics as an investigator. All other authors have nothing to disclose. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.",

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AU - Burdick, Katherine E.

AU - Millett, Caitlin E.

AU - Russo, Manuela

AU - Alda, Martin

AU - Alliey-Rodriguez, Ney

AU - Anand, Amit

AU - Balaraman, Yokesh

AU - Berrettini, Wade

AU - Bertram, Holli

AU - Calabrese, Joseph R.

AU - Calkin, Cynthia

AU - Conroy, Carla

AU - Coryell, William

AU - DeModena, Anna

AU - Feeder, Scott

AU - Fisher, Carrie

AU - Frazier, Nicole

AU - Frye, Mark

AU - Gao, Keming

AU - Garnham, Julie

AU - Gershon, Elliot S.

AU - Glazer, Kara

AU - Goes, Fernando S.

AU - Goto, Toyomi

AU - Harrington, Gloria J.

AU - Jakobsen, Petter

AU - Kamali, Masoud

AU - Kelly, Marisa

AU - Leckband, Susan

AU - Løberg, Else Marie

AU - Lohoff, Falk W.

AU - Maihofer, Adam X.

AU - McCarthy, Michael J.

AU - McInnis, Melvin

AU - Morken, Gunnar

AU - Nievergelt, Caroline M.

AU - Nurnberger, John

AU - Oedegaard, Ketil J.

AU - Ortiz, Abigail

AU - Ritchey, Megan

AU - Ryan, Kelly

AU - Schinagle, Martha

AU - Schwebel, Candice

AU - Shaw, Martha

AU - Shilling, Paul

AU - Slaney, Claire

AU - Stapp, Emma

AU - Tarwater, Bruce

AU - Zandi, Peter

AU - Kelsoe, John R.

N1 - Funding Information: This work was supported by the US National Institutes of Mental Health and General Medical Sciences (MH92758 to JRK; MH100125 to KEB). KEB has served as an advisory board member to Dainippon Sumitomo Pharmaceutical Neuralstem, and Takeda- Lundbeck. JN has received funding as an investigator from Assurex and from Janssen. JRK has received funds from Pathway Genomics as an investigator. All other authors have nothing to disclose. Publisher Copyright: © 2020, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1–5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1–5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically.

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The association between lithium use and neurocognitive performance in patients with bipolar disorder

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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