ArticleNature communications2021
Pharmacological rescue in patient iPSC and mouse models with a rare DISC1 mutation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Pooled it
- Elevated Plasma DISC1 Levels Are Associated With Motivational Deficits in Medication-Free Patients With Major Depressive Disorder: An Exploratory Study.PsyCh journal · 2026Article
- DISC1 Protects Against Zika Virus Infection and Long-Term Neurological Damage Through AMPK-mTOR-Mediated Autophagy.Nature communications · 2025Article
- Integrating genetic regulation and schizophrenia-specific splicing quantitative expression with GWAS prioritizes novel risk genes for schizophrenia.Translational psychiatry · 2025Article
- Cross-species analysis of adult hippocampal neurogenesis reveals human-specific gene expression but convergent biological processes.Nature neuroscience · 2025Article
- miRNA profiling of hiPSC-derived neurons from monozygotic twins discordant for schizophrenia.Schizophrenia (Heidelberg, Germany) · 2025Article
- Non-Invasive Quality Control of Organoid Cultures Using Mesofluidic CSTR Bioreactors and High-Content Imaging.Advanced materials technologies · 2025Article
- NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.International journal of molecular sciences · 2024Review
- Non-invasive label-free imaging analysis pipeline for in situ characterization of 3D brain organoids.Scientific reports · 2024Article
- Non-Invasive Label-free Analysis Pipeline for In Situ Characterization of Differentiation in 3D Brain Organoid Models.Research square · 2024Article
- Defined co-cultures of glutamatergic and GABAergic neurons with a mutation in DISC1 reveal aberrant phenotypes in GABAergic neurons.BMC neuroscience · 2024Article
- Genetics of human brain development.Nature reviews. Genetics · 2024Review
- Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study.Journal of translational medicine · 2023Article
- Adolescent neurostimulation of dopamine circuit reverses genetic deficits in frontal cortex function.bioRxiv : the preprint server for biology · 2023Article
- Biological and structural phenotypes associated with neurodevelopmental outcomes in congenital heart disease.Translational pediatrics · 2023Review
- Opportunities and limitations for studying neuropsychiatric disorders using patient-derived induced pluripotent stem cells.Molecular psychiatry · 2023Review
- Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders.Neuroscience applied · 2023Review
- Bassoon controls synaptic vesicle release via regulation of presynaptic phosphorylation and cAMP.EMBO reports · 2022Article
- Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells.Cell stem cell · 2021Article
- Applying stem cells and CRISPR engineering to uncover the etiology of schizophrenia.Current opinion in neurobiology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
23 authors at 9 institutions in 4 countries.
Funding
Abstract
We previously identified a causal link between a rare patient mutation in DISC1 (disrupted-in-schizophrenia 1) and synaptic deficits in cortical neurons differentiated from isogenic patient-derived induced pluripotent stem cells (iPSCs). Here we find that transcripts related to phosphodiesterase 4 (PDE4) signaling are significantly elevated in human cortical neurons differentiated from iPSCs with the DISC1 mutation and that inhibition of PDE4 or activation of the cAMP signaling pathway functionally rescues synaptic deficits. We further generated a knock-in mouse line harboring the same patient mutation in the Disc1 gene. Heterozygous Disc1 mutant mice exhibit elevated levels of PDE4s and synaptic abnormalities in the brain, and social and cognitive behavioral deficits. Pharmacological inhibition of the PDE4 signaling pathway rescues these synaptic, social and cognitive behavioral abnormalities. Our study shows that patient-derived isogenic iPSC and humanized mouse disease models are integral and complementary for translational studies with a better understanding of underlying molecular mechanisms.
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Registered trials
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.