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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The authors thank the patient participants without whom this work would not be possible.
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JRK organized the consortium from which the data were generated. KEB conceived of the presented idea. KEB, CEM and MR participated in data analysis, interpretation of results, as well as the writing and critical review of the manuscript. MA, NA, AA, YB, WB, HB, JRC, C Calkin, C Conroy, WC, AD, SF, CF, NF, MF, KG, JG, ESG, KG, FSG, TG, GM, GJH, PJ, M Kamali, M Kelly, SL, EML, FWL, AXM, MJM, MM, CMN, JN, KJO, AO, MR, KR, M Schinagle, CS, M Shaw, PS, CS, ES, BT, and PZ assisted in data collection and review of the manuscript.
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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.
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Burdick, K.E., Millett, C.E., Russo, M. et al. The association between lithium use and neurocognitive performance in patients with bipolar disorder. Neuropsychopharmacol. 45, 1743–1749 (2020). https://doi.org/10.1038/s41386-020-0683-2
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DOI: https://doi.org/10.1038/s41386-020-0683-2
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