Evidence map›Paper›PMID 25522399›Full record

ArticleThe international journal of neuropsychopharmacology2014

Bimodal effect of lithium plasma levels on hippocampal glutamate concentrations in bipolar II depression: a pilot study.

Marcus V Zanetti, Maria C Otaduy, Rafael T de Sousa, Wagner F Gattaz, Geraldo F Busatto, Claudia C Leite, Rodrigo Machado-Vieira

Open access · goldAbstract readControlled Clinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Article in The international journal of neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 7% of its field
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

9 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Glutamatergic Modulators in Depression.Harvard review of psychiatry
    Review
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

7 authors at 1 institution in 1 country.

Marcus V ZanettiMood Disorders Program, Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti, de Sousa, Gattaz, and Machado-Vieira); Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil (Drs Zanetti, Gattaz, Busatto, and Machado-Vieira); Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti and Busatto); Department of Radiology, University of Sao Paulo, Brazil (Drs Otaduy and Leite); Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD (Dr Machado-Vieira). zanetti.mv@gmail.com.
Maria C OtaduyMood Disorders Program, Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti, de Sousa, Gattaz, and Machado-Vieira); Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil (Drs Zanetti, Gattaz, Busatto, and Machado-Vieira); Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti and Busatto); Department of Radiology, University of Sao Paulo, Brazil (Drs Otaduy and Leite); Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD (Dr Machado-Vieira).
Rafael T de SousaMood Disorders Program, Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti, de Sousa, Gattaz, and Machado-Vieira); Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil (Drs Zanetti, Gattaz, Busatto, and Machado-Vieira); Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti and Busatto); Department of Radiology, University of Sao Paulo, Brazil (Drs Otaduy and Leite); Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD (Dr Machado-Vieira).
Wagner F GattazMood Disorders Program, Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti, de Sousa, Gattaz, and Machado-Vieira); Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil (Drs Zanetti, Gattaz, Busatto, and Machado-Vieira); Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti and Busatto); Department of Radiology, University of Sao Paulo, Brazil (Drs Otaduy and Leite); Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD (Dr Machado-Vieira).
Geraldo F BusattoMood Disorders Program, Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti, de Sousa, Gattaz, and Machado-Vieira); Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil (Drs Zanetti, Gattaz, Busatto, and Machado-Vieira); Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti and Busatto); Department of Radiology, University of Sao Paulo, Brazil (Drs Otaduy and Leite); Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD (Dr Machado-Vieira).
Claudia C LeiteMood Disorders Program, Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti, de Sousa, Gattaz, and Machado-Vieira); Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil (Drs Zanetti, Gattaz, Busatto, and Machado-Vieira); Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti and Busatto); Department of Radiology, University of Sao Paulo, Brazil (Drs Otaduy and Leite); Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD (Dr Machado-Vieira).
Rodrigo Machado-VieiraMood Disorders Program, Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti, de Sousa, Gattaz, and Machado-Vieira); Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil (Drs Zanetti, Gattaz, Busatto, and Machado-Vieira); Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil (Drs Zanetti and Busatto); Department of Radiology, University of Sao Paulo, Brazil (Drs Otaduy and Leite); Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD (Dr Machado-Vieira).
Universidade de São Paulo · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe hippocampus has been highly implicated in the pathophysiology of bipolar disorder (BD). Nevertheless, no study has longitudinally evaluated hippocampal metabolite levels in bipolar depression under treatment with lithium.

methodsNineteen medication-free BD patients (78.9% treatment-naïve and 73.7% with BD type II) presenting an acute depressive episode and 17 healthy controls were studied. Patients were treated for 6 weeks with lithium in an open-label trial. N-acetyl aspartate (NAA), creatine, choline, myo-Inositol, and glutamate levels were assessed in the left hippocampus before (week 0) and after (week 6) lithium treatment using 3T proton magnetic resonance spectroscopy (1H-MRS). The metabolite concentrations were estimated using internal water as reference and voxel segmentation for partial volume correction.

resultsAt baseline, acutely depressed BD patients and healthy controls exhibited similar hippocampal metabolites concentrations, with no changes after 6 weeks of lithium monotherapy. A significant correlation between antidepressant efficacy and increases in NAA concentration over time was observed. Also, there was a significant positive correlation between the changes in glutamate concentrations over follow-up and plasma lithium levels at endpoint. Mixed effects model analysis revealed a bimodal effect of lithium plasma levels in hippocampal glutamate concentrations: levels of 0.2 to 0.49 mmol/L (n=9) were associated with a decrease in glutamate concentrations, whereas the subgroup of BD subjects with "standard" lithium levels (≥ 0.50 mmol/L; n = 10) showed an overall increase in glutamate concentrations over time.

conclusionsThese preliminary results suggest that lithium has a bimodal action in hippocampal glutamate concentration depending on the plasma levels.

Indexed as

AdolescentAdultAffectAntimanic AgentsBipolar DisorderBrazilDrug MonitoringFemaleGlutamic AcidHippocampusHumansLithium CompoundsMalePilot ProjectsProton Magnetic Resonance SpectroscopyTime FactorsAntimanic AgentsGlutamic AcidLithium Compoundsbipolar disorderdepressionglutamatehippocampuslithiummagnetic resonance spectroscopy

Identifiers

PMID25522399
PMCPMC4438538
OpenAlexW2133960494

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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 OpenQuestion graph.