Evidence map›Paper›PMID 38697859›Full record

ReviewPharmacological reviews2024

New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview.

Analia Bortolozzi, Giovanna Fico, Michael Berk, Marco Solmi, Michele Fornaro, Joao Quevedo, Carlos A Zarate, Lars V Kessing, Eduard Vieta, Andre F Carvalho

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Pharmacological reviews, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  20. Patterns of lithium exposure and mortality in bipolar disorder: A population-based cohort study.European psychiatry : the journal of the Association of European Psychiatrists · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Analia BortolozziInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.).
Giovanna FicoInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.).
Michael BerkInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.).
Marco SolmiInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.).
Michele FornaroInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.).
Joao QuevedoInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.).
Carlos A ZarateInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.).
Lars V KessingInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.).
Eduard VietaInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.).
Andre F CarvalhoInstitut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.) andrefc7@hotmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium's effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium's various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer.

Indexed as

Lithium CompoundsAnimalsAntimanic AgentsBipolar DisorderGlycogen Synthase Kinase 3HumansNeuronal PlasticityAntimanic AgentsGlycogen Synthase Kinase 3Lithium Compounds

Identifiers

PMID38697859
PMCPMC11068842

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.