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 Table of Contents    
Year : 2011  |  Volume : 53  |  Issue : 2  |  Page : 177-178
Lithium not only stabilizes mood, it is also neuroprotective

Department of Psychiatry, Kasturba Medical College, Manipal, Karnataka - 576104, India

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Date of Web Publication30-Jun-2011

How to cite this article:
Praharaj SK. Lithium not only stabilizes mood, it is also neuroprotective. Indian J Psychiatry 2011;53:177-8

How to cite this URL:
Praharaj SK. Lithium not only stabilizes mood, it is also neuroprotective. Indian J Psychiatry [serial online] 2011 [cited 2022 Nov 28];53:177-8. Available from:


I read with interest the article "Old but still gold: lithium in stabilizing the mood" by Richard Balon published in Indian J Psychiatry in Apr-Jun 2009. [1] It aptly highlighted the advantages of lithium, which still remains the best choice as mood stabilizer in the current era when multitude of drugs have been advanced in the treatment of bipolar disorder. Lithium not only is effective in acute and prophylactic treatment for the episodes and reduces suicide in bipolar disorder, but also has neuroprotective properties.

There is an increased expression of the neuroprotective protein B-cell lymphoma/leukemia-2 (bcl-2) in the tissue following treatment with lithium. [2] The neuroprotective role of bis widely known; it not only protects against apoptotic and necrotic neuronal death but has also been demonstrated to increase the regeneration mammalian CNS axons. [2] Furthermore, lithium inhibits glycogen synthase kinase-3β (GSK-3β), [3] enzyme known to regulate the levels of phosphorylated tau bcatenin, both of which may play a role in the neurodegeneration observed in Alzheimer's disease. [2] Thus, the increases in bcl-2 levels and inhibition of GSK-3βmight in part account for its neuroprotective effects. Other possible modes of neuroprotection by lithium includes NMDA receptor blockade, reducing p53 expression, enhancement of camp response element binding (CREB) protein, brain-derived neurotrophic factor (BDNF) and activation of TrkB, downregulation of bax and caspase-3, and upregulation of homeodomain protein SIX1. [4],[5],[6] There are preliminary reports of neuroprotective role of lithium in brain ischemia, injury, infection, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, HIV-associated cognitive impairments, spinocerebellar ataxia, and cranial irradiation. [5]

The neuroprotective effects of lithium have also been demonstrated in various studies against diverse insults both in vitro and in vivo. Lithium treatment may inhibit apoptosis induced by many factors such as trophic factor withdrawal, amyloid b-peptide, etoposide, and camptothecin, decrease aluminum-induced translocation of cytochrome c, thapsigargin-induced stress on the endoplasmic reticulum, reduce mossy fiber sprouting caused by pilocarpine-induced limbic epilepsy, increase neurogenesis in the adult rodent hippocampus, prevent stress-induced alterations in the morphology and function of neurons. [4] These findings support that lithium has long-term beneficial effects in the treatment of bipolar disorder though its neuroprotective effects, other than its mood-stabilizing and antisuicidal properties. Although there are preliminary data regarding neuroprotective effects of sodium valproate, [7] lithium remains the only mood stabilizer that markedly increase bcl-2 levels in several brain areas. [2] Therefore, it is suggested that lithium should be first line of therapy in long-term treatment of bipolar disorder considering its unique anti-suicidal and neuroprotective effects. Also, in cases with partial response to lithium, with the exception of intolerable adverse effects, it may be continued along with other second line agents. Nevertheless, there are occasional instances of neurotoxic effects of lithium which are irreversible (known by the acronym SILENT, syndrome of irreversible Li-effectuated neurotoxicity), such as irreversible cerebellar syndrome, neuroleptic malignant syndrome, tardive dyskinesia, and Creutzfeldt-Jakob-like syndrome, which raises concern in its widespread usage. [5]

   References Top

1.Balon R. Old but still gold: Lithium in stabilizing the mood. Indian J Psychiatry 2009;51:157-8.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.Manji HK, Moore GJ, Chen G. Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Biol Psychiatry 1999;46:929-40.  Back to cited text no. 2
3.Stambolic V, Ruel L, Woodgett JR. Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signaling in intact cells. Curr Biol 1996;6:1664-8.  Back to cited text no. 3
4.Fountoulakis KN, Vieta E, Bouras C, Notaridis G, Giannakopoulos P, Kaprinis G, et al. A systematic review of existing data on long-term lithium therapy: Neuroprotective or neurotoxic? Int J Neuropsychopharmacol 2008;11:269-87.  Back to cited text no. 4
5.Machado-Vieira R, Manji HK, Zarate CA Jr. The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord 2009;2:92-109.  Back to cited text no. 5
6.Quiroz JA, Machado-Vieira R, Zarate CA Jr, Manji HK. Novel Insights into Lithium's Mechanism of Action: Neurotrophic and Neuroprotective Effects. Neuropsychobiology 2010;62:50-60.  Back to cited text no. 6
7.Chuang DM. The antiapoptotic actions of mood stabilizers: Molecular mechanisms and therapeutic potentials. Ann N Y Acad Sci 2005;1053:195-204.  Back to cited text no. 7

Correspondence Address:
Samir Kumar Praharaj
Department of Psychiatry, Kasturba Medical College, Manipal, Karnataka - 576104
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5545.82563

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