ArticleNature2014
Synaptic dysregulation in a human iPS cell model of mental disorders.
Registry-linked trialAbstract read
In one paragraph
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07427940 (Omic Profile in Autism Spectrum Disorder), which is not on this map. Cited by 352 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
352citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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.
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.
Omic Profile in Autism Spectrum Disorder: From Cellular Level Towards Future Treatments
Who cites it
352 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020Pooled it
- Modulation of Endoplasmic Reticulum Stress via CEBPB: A Potential Molecular Link to Therapeutic Action in Substance Use Disorders.CNS neuroscience & therapeutics · 2026Article
- Derivation of functional retinal endothelial cells from human pluripotent stem cells for therapeutics and modelling.Nature biomedical engineering · 2026Article
- Article
- Characterization of Electrophysiological and Transcriptomic Alterations in Patient-Derived Neurons from CHAMP1 Syndrome.bioRxiv : the preprint server for biology · 2026Article
- Development of a human iPSC-derived corticospinal tract-on-a-chip.Cell reports methods · 2026Article
- Biomarker for craving and acamprosate treatment response in patients with alcohol use disorder: insights from multi-omics.Molecular psychiatry · 2026Article
- Human-Derived Cellular Models in Psychiatry: A Focus on the Olfactory Neuroepithelium.Brain sciences · 2026Review
- Structural basis for the transport mechanism and cholesterol modulation of the human proline transporter.Nature communications · 2026Article
- From classic circuits to novel mechanisms: How lncRNA, neuroinflammation, and iPSC models address the translational crisis in PTSD research.Comprehensive psychoneuroendocrinology · 2026Review
- Hyperdynamic microtubule-based structural changes in Monocyte-Derived-Neuronal-like cells from patients with schizophrenia.Schizophrenia (Heidelberg, Germany) · 2026Article
- Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks.Nature communications · 2026Article
- Synaptic effects of interleukin-6 on human iPSC-derived dopaminergic neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- DISC1 mutant macaques capture behavioral and neural hallmarks of psychiatric disease.National science review · 2026Article
- A co-culture model of dopaminergic and glutamatergic neurons derived from patients with idiopathic schizophrenia reveals a hypodopaminergic phenotype.Molecular psychiatry · 2026Article
- How copy number variations shape brain developmental disorders: Unraveling the synaptic puzzle.Psychiatry and clinical neurosciences · 2026Review
- Article
- Unraveling the Morphological and Functional Maturation Mechanisms Underlying Human Neural Development Using iPSCs-Derived Neuronal Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exploring the roots of schizophrenia: Current research and future directions (Review).Experimental and therapeutic medicine · 2026Review
292 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors.
Zhexing Wen1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3].
Ha Nam Nguyen1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3].
Ziyuan Guo1] Department of Biology, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA [2].
Matthew A LalliNeuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, Biomolecular Science and Engineering Program, University of California, Santa Barbara, California 93106, USA.
Xinyuan Wang1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Yijing Su1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nam-Shik Kim1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Ki-Jun Yoon1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Jaehoon Shin1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Ce Zhang1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Georgia Makri1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
David Nauen1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Huimei Yu1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Elmer GuzmanNeuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, Biomolecular Science and Engineering Program, University of California, Santa Barbara, California 93106, USA.
Cheng-Hsuan Chiang1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nadine YoritomoDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kozo KaibuchiDepartment of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan.
Jizhong Zou1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kimberly M Christian1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Linzhao Cheng1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Christopher A Ross1] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Russell L Margolis1] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Gong ChenDepartment of Biology, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Kenneth S KosikNeuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, Biomolecular Science and Engineering Program, University of California, Santa Barbara, California 93106, USA.
Hongjun Song1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [4] The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Guo-li Ming1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [4] The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Funding
Training Program in Cellular and Molecular MedicineT32GM008752 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI RAO, RAJINI · 2000 to 2019
$11.7MDevelopment of new neurons in the adult brainR01NS047344 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SONG, HONGJUN · 2003 to 2011
$3.4MCalcium signaling in neuronal navigationR01NS048271 · NINDS · JOHNS HOPKINS UNIVERSITY · PI MING, GUO-LI · 2004 to 2014
$3.2MLocal circuitry mechanisms regulating adult hippocampal neurogenesisR37NS047344 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI SONG, HONGJUN · 2013 to 2019
$2.9MCircuitry mechanisms underlying normal and aberrant adult hippocampal neurogenesisR01MH105128 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI MING, GUO-LI · 2014 to 2018
$2.0MGABAergic Synapse Assembly: Extrasynaptic GABAAR TargetingR01MH083911 · NIMH · PENNSYLVANIA STATE UNIVERSITY, THE · PI CHEN, GONG · 2010 to 2014
$1.8MConverting Alzheimer's reactive astrocytes into functional neuronsR01AG045656 · NIA · PENNSYLVANIA STATE UNIVERSITY, THE · PI CHEN, GONG · 2013 to 2017
$1.6MRegulation of adult neurogenesis during agingR01AG024984 · NIA · JOHNS HOPKINS UNIVERSITY · PI SONG, HONGJUN · 2004 to 2008
$1.6MNeural Development of Human Induced Pluripotent Stem Cells from Schizophrenia PatR33MH087874 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SONG, HONGJUN · 2011 to 2012
$805kNeural Development of Human Induced Pluripotent Stem Cells from Schizophrenia PatR21MH087874 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SONG, HONGJUN · 2009 to 2010
$488kImpact of Bisphenol A on neural stem cells and development in the adult brainR21ES021957 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI SONG, HONGJUN · 2012 to 2013
$441kCircuitry mechanisms regulating adult hippocampal neurogenesisR56NS047344 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SONG, HONGJUN · 2012 to 2012
$405kNIA NIH HHS AG045656NIA NIH HHS R01 AG024984NIA NIH HHS R01 AG045656NIEHS NIH HHS R21 ES021957NIGMS NIH HHS T32 GM008752NIMH NIH HHS F31 MH102978NIMH NIH HHS MH087874NIMH NIH HHS MH102978NIMH NIH HHS R01 MH083911NIMH NIH HHS R01 MH105128NIMH NIH HHS R21 MH087874NIMH NIH HHS R21 MH092740NIMH NIH HHS R33 MH087874NINDS NIH HHS NS047344NINDS NIH HHS NS048271NINDS NIH HHS R01 NS047344NINDS NIH HHS R01 NS048271NINDS NIH HHS R37 NS047344NINDS NIH HHS R56 NS047344
Abstract
Dysregulated neurodevelopment with altered structural and functional connectivity is believed to underlie many neuropsychiatric disorders, and 'a disease of synapses' is the major hypothesis for the biological basis of schizophrenia. Although this hypothesis has gained indirect support from human post-mortem brain analyses and genetic studies, little is known about the pathophysiology of synapses in patient neurons and how susceptibility genes for mental disorders could lead to synaptic deficits in humans. Genetics of most psychiatric disorders are extremely complex due to multiple susceptibility variants with low penetrance and variable phenotypes. Rare, multiply affected, large families in which a single genetic locus is probably responsible for conferring susceptibility have proven invaluable for the study of complex disorders. Here we generated induced pluripotent stem (iPS) cells from four members of a family in which a frameshift mutation of disrupted in schizophrenia 1 (DISC1) co-segregated with major psychiatric disorders and we further produced different isogenic iPS cell lines via gene editing. We showed that mutant DISC1 causes synaptic vesicle release deficits in iPS-cell-derived forebrain neurons. Mutant DISC1 depletes wild-type DISC1 protein and, furthermore, dysregulates expression of many genes related to synapses and psychiatric disorders in human forebrain neurons. Our study reveals that a psychiatric disorder relevant mutation causes synapse deficits and transcriptional dysregulation in human neurons and our findings provide new insight into the molecular and synaptic etiopathology of psychiatric disorders.
Indexed as
AnimalsCell DifferentiationFibroblastsGlutamineHumansInduced Pluripotent Stem CellsMaleMental DisordersMiceMutant ProteinsMutationNerve Tissue ProteinsNeuronsPedigreePresynaptic TerminalsProsencephalonDISC1 protein, humanGlutamineMutant ProteinsNerve Tissue Proteins
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Read underepoch 390
Registered trials
NCT07427940ClinicalTrials.gov
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.