A systematic review of existing data on long-term lithium therapy: neuroprotective or neurotoxic?

Fountoulakis, Konstantinos Ν.; Vieta, Eduard; Bouras, Constantin; Notaridis, Grigorios; Giannakopoulos, Pantéleimon; Kaprinis, George; Akiskal, Hagop

doi:10.1017/s1461145707007821

Cited by 71 publications

(63 citation statements)

References 196 publications

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“…It is well known that the risk of recurrence of affective episodes increases with the number of prior affective episodes and some evidence further suggests that the rate of dementia also increases with the number of affective episodes as the illness goes on [14]. The pathogenetic mechanisms are unknown but a key hypothesis has emerged in relation to glycogen synthase kinase 3B, which is a key enzyme in the metabolism of amyloid precursor protein and in the phosphorylation of the tau protein involved in the pathogenesis of Alzheimer's disease [15,16]. Preliminary new data suggest that glycogen synthase kinase 3B activity is increased in patients with mild cognitive impairment and in Alzheimer's disease [17] and also in patients with late-life depression [18].…”

Section: Bd Dementia and Lithiummentioning

confidence: 99%

“…Preliminary new data suggest that glycogen synthase kinase 3B activity is increased in patients with mild cognitive impairment and in Alzheimer's disease [17] and also in patients with late-life depression [18]. Interestingly, among the many effects of lithium, it inhibits glycogen synthase kinase 3 [15,16]. Accordingly, findings from large register-based studies suggest that continued treatment with lithium reduces the risk of developing dementia in the long run among patients with BDs [19,20].…”

Section: Bd Dementia and Lithiummentioning

confidence: 99%

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Bipolar Disorder in the Elderly

et al. 2011

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Over 1200 participants from a wide array of psychogeriatric disciplines attended the 15th world congress of the International Psychogeriatric Association (IPA) in The Netherlands. In previous years, the meetings and activities of the IPA were strongly focused on research restricted to diagnosis and care of individuals with dementia. In recent years, there has been a shift of attention towards other psychiatric disorders in the elderly such as schizophrenia, substance abuse and bipolar disorder, which were for a long time nearly invisible in the scientific literature. The symposium venue was located in The Hague, a typical Dutch town not far from the coastline and home to several famous international institutions in the field of peace and justice. This successful meeting with the theme ‘Reinventing Aging through Innovation, Care, Research, Technology’ was co-chaired by Anne Margriet Pot (Professor of Geropsychology, Amsterdam, The Netherlands) and Frans Verhey (Professor of Neuropsychiatry, Maastricht, The Netherlands). A special symposium on ‘Bipolar Disorder in the Elderly’ also took place during the 4-day meeting. This symposium was organized by The Netherlands Psychiatric Association, Faculty of Old Age Psychiatry and is an example of a neglected topic in geriatric mental health and represents the important diverse mental disorders that a large proportion of older adults and their families can experience. The symposium was co-chaired by Max Stek, Professor of Old Age Psychiatry and Chair of the Dutch Faculty of Old Age from The Netherlands and Martha Sajatovic from the USA. Presenting faculty were Ralph Kupka and Annemiek Dols from The Netherlands and Lars Kessing from Denmark.

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Section: Bd Dementia and Lithiummentioning

confidence: 99%

Section: Bd Dementia and Lithiummentioning

confidence: 99%

Bipolar Disorder in the Elderly

et al. 2011

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“…More and more glial, neuroendocrine and immunologic dysfunctions seem to be recognised as contributing to mood disorders' pathogenesis [5][6][7][8]. In this context possible cytoprotective capacity of lithium salts, although debated, seems very promising for both neuron and glial regeneration and for possible preservation of the intact function of the immune cells [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…Cytoprotective effects of Li are mainly attributed to: (1) increasing amounts of cytoprotective proteins such as Bcl-2 and decreasing proapoptotic proteinsBax and p53, (2) inhibition of glycogen synthetase kinase-3 (GSK-3) and (3) protein kinase C (PKC) activation [9,[13][14][15][16]. Thus, it is conceivable that affecting the same mechanisms of survival or death Li + may exert a cytoprotective effect on other cell types.…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective effect of lithium against spontaneous and induced apoptosis of lymphoid cell line MOLT-4.

Pietruczuk

Jóźwik²,

Rückemann-Dziurdzińska³

et al. 2010

Folia Histochem Cytobiol.

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Lithium (Li) is still useful in the treatment of bipolar disorder. Cellular mechanisms of Li action are not fully understood and include some cytoprotective properties. Data concerning Li effect on the apoptotic mechanisms in cells other than neurons are fragmentary and contradictory. We have investigated anti-apoptotic activity of Li in a lymphoid derived MOLT-4 cell line. Spontaneous and camptothecin-induced apoptosis was analyzed in cells treated with 0-20 mM Li carbonate. Early apoptosis was identified as significant mitochondrial depolarization (JC-1 staining). Later stages of apoptosis were estimatied with annexin V binding and by the proportion of cells containing sub-G1 amounts of DNA (PI staining). We have observed a biphasic effect of Li on the proportion of spontaneously apoptotic cells;namely, low (therapeutic) concentrations of Li had a significant effect stabilizing the mitochondrial membrane polarization, while 10 and 20mM Li increased apoptosis. The latter could be seen both as mitochondrial depolarization as well as an increased proportion of sub-G1 cells, accompanied by reduced proportion of S phase cells. Li at concentrations above 2 mM had a significant, dosedependent, anti-apoptotic effect on the cells undergoing camptothecin induced apoptosis. In conclusion, demonstrated cytoprotective effect of Li is at least partially related to stabilization of mitochondrial membrane potential and to the reduction of DNA damaging effects in proliferating cells; both may form part of the mechanism through which Li is useful in therapy of bipolar disorder, but may have more general consequences.

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“…The literature is inconclusive regarding this, although evidence is mounting for a neurotoxic effect. 4,5 Lithium toxicity typically presents to the general hospital and general physicians will be aware of the therapeutic range for lithium. However, lithium has been known to cause neurotoxicity even at therapeutic levels 6 and its endocrine effects may lead to deterioration in both physical and mental health.…”

mentioning

confidence: 99%