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

Psychiatry and Psychology

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

2 Scopus citations

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 (US)
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
State	Published - Sep 1 2020

ASJC Scopus subject areas

Pharmacology
Psychiatry and Mental health

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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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title = "The association between lithium use and neurocognitive performance in patients with bipolar disorder",

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.",

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

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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.

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

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