Evidence map›Paper›PMID 25733313›Full record

ArticleMolecular psychiatry2015

Characterization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities.

J M Madison, F Zhou, A Nigam, A Hussain, D D Barker, R Nehme, K van der Ven, J Hsu, P Wolf, M Fleishman and 15 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 3 pooled it
11.1field-weighted citation impact, top 1% 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

104 citing papers in PubMed, 3 syntheses or guidelines pooled it, 187 citations in OpenAlex.

  1. Pooled it
  2. Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020
    Pooled it
  3. Pooled it
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  17. RNA Biomarkers in Bipolar Disorder and Response to Mood Stabilizers.International journal of molecular sciences · 2023
    Review
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44 more citing papers are in PubMed but not listed here.

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

25 authors at 3 institutions in 1 country.

J M Madison1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA [3] Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
F Zhou1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA.
A Nigam1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
A Hussain1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA.
D D BarkerStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
R Nehme1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
K van der VenPsychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA.
J Hsu1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA.
P Wolf1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA [3] Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
M Fleishman1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA.
C O'DushlaineStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
S RoseStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
K ChambertStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
F H LauDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
T AhfeldtDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
E H Rueckert1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA [3] Chemical Neurobiology Laboratory, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
S D SheridanChemical Neurobiology Laboratory, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
D M Fass1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA [3] Chemical Neurobiology Laboratory, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
J Nemesh1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Department of Genetics, Harvard Medical School, Boston, MA, USA.
T E Mullen1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Department of Genetics, Harvard Medical School, Boston, MA, USA.
L DaheronDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
S McCarroll1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Department of Genetics, Harvard Medical School, Boston, MA, USA.
P Sklar1] Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
R H Perlis1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA [3] Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA [4] Chemical Neurobiology Laboratory, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
S J Haggarty1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA [3] Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA [4] Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA [5] Chemical Neurobiology Laboratory, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute · USHarvard University · USCenter for Human Genetics · US

Funding

Genomics-Guided Characterization of iPS Cells from Common Mental IllnessesR33MH087896 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI HAGGARTY, STEPHEN J · 2011 to 2012
$872k
In vitro and in vivo study of simvastatin plus lithium in bipolar depressionR21MH093958 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI HAGGARTY, STEPHEN J, PERLIS, ROY H. · 2012 to 2013
$674k
NIMH NIH HHS R21 MH093958NIMH NIH HHS R21MH093958NIMH NIH HHS R33 MH087896NIMH NIH HHS R33MH087896
6 · The paper itself

Abstract

Bipolar disorder (BD) is a common neuropsychiatric disorder characterized by chronic recurrent episodes of depression and mania. Despite evidence for high heritability of BD, little is known about its underlying pathophysiology. To develop new tools for investigating the molecular and cellular basis of BD, we applied a family-based paradigm to derive and characterize a set of 12 induced pluripotent stem cell (iPSC) lines from a quartet consisting of two BD-affected brothers and their two unaffected parents. Initially, no significant phenotypic differences were observed between iPSCs derived from the different family members. However, upon directed neural differentiation, we observed that CXCR4 (CXC chemokine receptor-4) expressing central nervous system (CNS) neural progenitor cells (NPCs) from both BD patients compared with their unaffected parents exhibited multiple phenotypic differences at the level of neurogenesis and expression of genes critical for neuroplasticity, including WNT pathway components and ion channel subunits. Treatment of the CXCR4(+) NPCs with a pharmacological inhibitor of glycogen synthase kinase 3, a known regulator of WNT signaling, was found to rescue a progenitor proliferation deficit in the BD patient NPCs. Taken together, these studies provide new cellular tools for dissecting the pathophysiology of BD and evidence for dysregulation of key pathways involved in neurodevelopment and neuroplasticity. Future generation of additional iPSCs following a family-based paradigm for modeling complex neuropsychiatric disorders in conjunction with in-depth phenotyping holds promise for providing insights into the pathophysiological substrates of BD and is likely to inform the development of targeted therapeutics for its treatment and ideally prevention.

Indexed as

Bipolar DisorderCell DifferentiationCells, CulturedCytokinesDNA Copy Number VariationsFamily HealthFemaleGene ExpressionGlycogen Synthase Kinase 3HumansInduced Pluripotent Stem CellsIntercellular Signaling Peptides and ProteinsMaleMembrane PotentialsNeuronsPolymorphism, Single NucleotideCXCR4 protein, humanCytokinesGlycogen Synthase Kinase 3Intercellular Signaling Peptides and ProteinsReceptors, CXCR4RNA, MessengerTranscription Factors

Identifiers

PMID25733313
PMCPMC4440839
OpenAlexW2011526626

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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.