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Pharmacotherapy in Psychiatry and Neurology/Farmakoterapia w Psychiatrii i Neurologii
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1/2024
vol. 40
 
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Review article

The mechanisms of lithium action – an update

Janusz Rybakowski
1

  1. Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland; Corresponding member of the Polish Academy of Sciences Klinika Psychiatrii Dorosłych, Uniwersytet Medyczny w Poznaniu, Poznań, Polska; Członek korespondent Polskiej Akademii Nauk
Farmakoterapia w Psychiatrii i Neurologii 2024, 40 (1), 13–23
Online publish date: 2024/08/01
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1. Abu-Hijleh FA, Prashar S, Joshi H, Sharma R, Frey BN, Mishra RK. Novel mechanism of action for the mood stabilizer lithium. Bipolar Disord 2021; 23: 76–83.
2. Amare AT, Schubert KO, Hou L, Clark SR, Papiol S, Cearns M et al. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder. Mol Psychiatry 2021; 26: 2457–70.
3. Amare AT, Thalamuthu A, Schubert KO, Fullerton JM, Ahmed M, Hartmann S et al. Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. Mol Psychiatry 2023 Jul 11. DOI: 10.1038/s41380.023.02149–1. Online ahead of print.
4. Ananth M, Bartlett EA, DeLorenzo C, Lin X, Kunkel L, Vadhan NP et al. Prediction of lithium treatment response in bipolar depression using 5-HTT and 5-HT1A PET. Eur J Nucl Med Mol Imaging 2020; 47: 2417–28.
5. Brown KM, Tracy DK. Lithium: the pharmacodynamic actions of the amazing ion. Ther Adv Psychopharmacol 2013; 3: 163–76.
6. Cade JFK. Lithium salts in the treatment of psychotic excitement. Med J Aust 1949; 36: 349–52.
7. Cattane N, Courtin C, Mombelli E, Maj C, Mora C, Etain B et al. Transcriptomics and miRNomics data integration in lymphoblastoid cells highlights the key role of immune-related functions in lithium treatment response in Bipolar disorder. BMC Psychiatry 2022; 22: 665.
8. Cearns M, Amare AT, Schubert KO, Thalamuthu A, Frank J, Streit F et al. Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM. Br J Psychiatry 2022; 221: 494.
9. Coombes BJ, Millischer V, Batzler A, Larrabee B, Hou L, Papiol S et al. Association of Attention-Deficit/Hyperactivity Disorder and depression polygenic scores with lithium response: a consortium for lithium genetics study. Complex Psychiatry 2021; 7: 80–9.
10. Coutts F, Palmos AB, Duarte RRR, de Jong S, Lewis CM, Dima D et al. The polygenic nature of telomere length and the anti-ageing properties of lithium. Neuropsychopharmacology 2019; 44: 757–65.
11. Dembińska-Krajewska D, Kliwicki S, Chłopocka-Woźniak M, Rybakowski J. Skuteczność profilaktycznego stosowania litu w chorobie afektywnej dwubiegunowej a cechy schizotypii. Farmakoter Psychiatr Neurol 2012; 28: 153–8.
12. Dopierała E, Chrobak A, Tereszko A, Rybakowski J. Wpływ litu na rytm okołodobowy oceniany za pomocą Skali Ranności u pacjentów z chorobą afektywną dwubiegunową w okresie remisji. Farmakot Psychiatr Neurol 2017; 33: 9–20.
13. Federoff M, McCarthy MJ. Sleep and circadian rhythm disruption is corrected by lithium in a case of bipolar disorder with familial BRCA1 mutation. Bipolar Disord 2021; 23: 101–3.
14. Federoff M, McCarthy MJ, Anand A, Berrettini WH, Bertram H, Bhattacharjee A et al. Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder. Bipolar Disord 2022; 24: 521–9.
15. Fenech RK, Hamstra SI, Finch MS, Ryan CR, Marko DM, Roy BD et al. Low-dose lithium supplementation Influences GSK3β activity in a brain region specific manner in C57BL6 male mice. J Alzheimers Dis 2023; 91: 615–26.
16. Ferensztajn-Rochowiak E, Kurczewska E, Rubiś B, Lulkiewicz M, Hołysz H, Rybakowski F et al. Decreased leucocyte telomere length in male patients with chronic bipolar disorder: lack of effect of long-term lithium treatment. Acta Neuropsychiatr 2021; 33: 299–306.
17. Freund N, Haussleiter I. Bipolar chronobiology in men and mice: a narrative review Brain Sci 2023; 13: 738.
18. Gao K, Kaye NM, Ayati M, Koyuturk M, Calabrese JR, Christian E et al. Divergent directionality of immune cell-specific protein expression between bipolar lithium responders and non-responders revealed by enhanced flow cytometry. Medicina (Kaunas) 2023; 59: 120.
19. Herrera-Rivero M, Gutiérrez-Fragoso K; International Consortium on Lithium Genetics (ConLi+Gen); Kurtz J, Baune BT. Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder. Transl Psychiatry 2024; 14: 174.
20. Hou L, Heilbronner U, Degenhardt F, Adli M, Akiyama K, Akula N et al. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet 2016; 387: 1085–93.
21. International Consortium on Lithium Genetics (ConLi+Gen), Amare AT, Schubert KO, Hou L, Clark SR, Papiol S et al. Association of polygenic score for schizophrenia and HLA antigen and inflammation genes with response to lithium in bipolar affective disorder: a genome-wide association study. JAMA Psychiatry 2018; 75: 65–74.
22. Jacobs A, Hagin M, Shugol M, Shomron N, Pillar N, Fañanás L et al. The black sheep of the family – whole-exome sequencing in family of lithium response discordant bipolar monozygotic twins. Eur Neuropsychopharmacol. 2020; 34: 19–27.
23. Khayachi A, Ase A, Liao C, Kamesh A, Kuhlmann N, Schorova L et al. Chronic lithium treatment alters the excitatory/ inhibitory balance of synaptic networks and reduces mGluR5-PKC signalling in mouse cortical neurons. J Psychiatry Neurosci 2021; 46: E402-E414.
24. Khayachi A, Abuzgaya M, Liu Y, Jiao C, Dejgaard K, Schorova L et al. Molecular signatures of hyperexcitability and lithium responsiveness in bipolar disorder patient neurons provide alternative therapeutic strategies. eBioMedicine 2024; 101 (w druku).
25. Le Clerc S, Lombardi L, Baune BT, Amare AT, Schubert KO, Hou L et al. HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders. Sci Rep 2021; 11: 17823.
26. Lundberg M, Biernacka JM, Lavebratt C, Druliner B, Ryu E, Geske J et al. Expression of telomerase reverse transcriptase positively correlates with duration of lithium treatment in bipolar disorder. Psychiatry Res. 2020; 286: 112865.
27. Marie-Claire C, Lejeune FX, Mundwiller E, Ulveling D, Moszer I, Bellivier F et al. A DNA methylation signature discriminates between excellent and non-response to lithium in patients with bipolar disorder type 1. Sci Rep. 2020; 10: 12239.
28. Marie-Claire C, Courtin C, Bellivier F, Scott J, Etain B. Methylomic biomarkers of lithium response in bipolar disorder: a proof of transferability study. Pharmaceuticals 2022; 15: 133.
29. Marie-Claire C, Courtin C, Bellivier F, Gard S, Leboyer M, Scott J, Etain B. Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study. Int J Bipolar Disord 2023; 11: 16.
30. McCarthy MJ, Wei H, Nievergelt CM, Stautland A, Maihofer AX, Welsh DK et al. Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder. Neuropsychopharmacology 2019; 44: 620–628.
31. Milanesi E, Voinsky I, Hadar A, Srouji A, Maj C, Shekhtman T et al. RNA sequencing of bipolar disorder lymphoblastoid cell lines implicates the neurotrophic factor HRP-3 in lithium’s clinical efficacy. World J Biol Psychiatry 2019; 20: 449–461.
32. Miranda A, Shekhtman T, McCarthy M, DeModena A, Leckband SG, Kelsoe JR. Study of 45 candidate genes suggests CACNG2 may be associated with lithium response in bipolar disorder. J Affect Disord. 2019; 248: 175–179.
33. Mishra HK, Mandyam AD, Trenet W, Wei H, Nievergelt CM, Maihofer AX et al. Neural progenitor cells derived from lithium responsive and non-responsive bipolar disorder patients exhibit distinct sensitivity to cell death following methamphetamine. Neuropharmacology 2023a; 226: 109410.
34. Mishra HK, Wei H, Rohr KE, Ko I, Nievergelt CM, Maihofer AX et al. Contributions of circadian clock genes to cell survival in fibroblast models of lithium-responsive bipolar disorder. Eur Neuropsychopharmacol 2023b; 74: 1–14.
35. Mizrahi L, Choudhary A, Ofer P, Goldberg G, Milanesi E, Kelsoe JR et al. Immunoglobulin genes expressed in lymphoblastoid cell lines discern and predict lithium response in bipolar disorder patients. Mol Psychiatry 2023; 28: 4280–4293.
36. Mullins N, Forstner AJ, O’Connell KS, Coombes B, Coleman JRI, Qiao Z et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nat Genet 2021; 53: 817–29.
37. Mutz J, Wong WLE, Powell TR, Young AH, Dawe GS, Lewis CM. The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality. Geroscience 2024 Mar 28. DOI: 10.1007/s11357.024.01142-y. Online ahead of print.
38. Müller-Oerlinghausen B. Lithium long-term treatment – does it act via serotonin? Pharmacopsychiatry 1985; 18: 214–17.
39. Osete JR, Akkouh IA, Ievglevskyi O, Vandenberghe M, de Assis DR, Ueland T et al. Transcriptional and functional effects of lithium in bipolar disorder iPSC-derived cortical spheroids. Mol Psychiatry 2023; 28: 3033–43.
40. Ou AH, Rosenthal SB, Adli M, Akiyama K, Akula N, Alda M et al. Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study. Transl Psychiatry 2024; 14: 109.
41. Perlis RH, Purcell S, Fagerness J, Kirby A, Petryshen TL, Fan J et al. Family-based association study of lithium-related and other candidate genes in bipolar disorder. Arch Gen Psychiatry. 2008; 65: 53–61.
42. Piguel NH, Yoon S, Gao R, Horan KE, Garza JC, Petryshen TL et al. Lithium rescues dendritic abnormalities in Ank3 deficiency models through the synergic effects of GSK3β and cyclic AMP signaling pathways. Neuropsychopharmacology 2023; 48: 1000–10.
43. Pisanu C, Congiu D, Manchia M, Caria P, Cocco C, Dettori T et al. Differences in telomere length between patients with bipolar disorder and controls are influenced by lithium treatment. Pharmacogenomics 2020; 21: 533–40.
44. Price JB, Yates CG, Morath BA, Van De Wakker SK, Yates NJ, Butters K et al. Lithium augmentation of ketamine increases insulin signaling and antidepressant-like active stress coping in a rodent model of treatment-resistant depression. Transl Psychiatry 2021; 11: 598.
45. Rana AK, Sharma S, Patial V, Singh D. Lithium therapy subdues neuroinflammation to maintain pyramidal cells arborization and rescues neurobehavioural impairments in ovariectomized rats. Mol Neurobiol 2022; 59: 1706–23.
46. Rybakowski J. Lit – niezwykły lek w psychiatrii. Wydawnictwo Termedia, Poznań, 2019. https://www.termedia.pl/Ksiazka/-279
47. Rybakowski J. Leczenie litem – stan wiedzy na rok 2020. Psychiatr Pol 2020; 54: 1047–66.
48. Rybakowski J. Lit w chorobach afektywnych – aktualizacja. Farmakoter Psychiatr Neurol 2023; 39: 103–13.
49. Saha S, Krishnan H, Raghu P. IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signaling by lithium. Life Sci Alliance 2023; 7: e202302425.
50. Sakrajda K, Szczepankiewicz A. Inflammation-related changes in mood disorders and the immunomodulatory role of lithium. Int J Mol Sci 2021; 22: 1532.
51. Santos R, Linker SB, Stern S, Mendes APD, Shokhirev MN, Erikson G et al. Deficient LEF1 expression is associated with lithium resistance and hyperexcitability in neurons derived from bipolar disorder patients. Mol Psychiatry 2021; 26: 2440–56.
52. Schubert KO, Thalamuthu A, Amare AT, Frank J, Streit F, Adli M, Akula N et al. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients. Transl Psychiatry 2021; 11: 606.
53. Szałach ŁP, Lisowska KA, Cubała WJ, Barbuti M, Perugi G. The immunomodulatory effect of lithium as a mechanism of action in bipolar disorder. Front Neurosci 2023; 17: 1213766.
54. Tsai SY, Kuo CJ, Sajatovic M, Huang YJ, Chen PH, Chung KH. Lithium exposure and chronic inflammation with activated macrophages and monocytes associated with atherosclerosis in bipolar disorder. J Affect Disord 2022; 314: 233–40.
55. Wang W, Lu D, Shi Y, Wang Y. Exploring the neuroprotective effects of lithium in ischemic stroke: A literature review. Int J Med Sci 2024; 21: 284-298.

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