Evidence map›Paper›PMID 30446636›Full record

ArticleTranslational psychiatry2017

Cerebral organoids reveal early cortical maldevelopment in schizophrenia-computational anatomy and genomics, role of FGFR1.

E K Stachowiak, C A Benson, S T Narla, A Dimitri, L E Bayona Chuye, S Dhiman, K Harikrishnan, S Elahi, D Freedman, K J Brennand and 2 more

Open access · goldAbstract read
In one paragraph

Article in Translational psychiatry, 2017. 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
6.0field-weighted citation impact, top 3% 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, 178 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Using Brain Organoids to Explore Human Neurobiology.Cellular and molecular neurobiology · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Repurposing medications to prevent psychosis.Npj mental health research · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Modelling human brain development and disease with organoids.Nature reviews. Molecular cell biology · 2025
    Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

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

12 authors at 4 institutions in 1 country.

E K StachowiakDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA. eks1@buffalo.edu.
C A BensonDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
S T NarlaDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
A DimitriDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
L E Bayona ChuyeDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
S DhimanDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
K HarikrishnanDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
S ElahiDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
D FreedmanDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
K J BrennandIcahn School of Medicine at Mount Sinai, Departments of Psychiatry and Neuroscience, New York, NY, USA.ORCID 0000-0003-0993-5956
P SarderDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
M K StachowiakDepartment of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA. mks4@buffalo.edu.
University at Buffalo, State University of New York · USBuffalo State University · USIcahn School of Medicine at Mount Sinai · USSUNY Fredonia · US

Funding

Higher Order Chromatin and Genetic Risk for SchizophreniaR01MH106056 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, BRENNAND, KRISTEN JENNIFER · 2015 to 2023
$6.7M
Contrasting causal microRNAs in forebrain and midbrain COS hiPSC neural cellsR01MH101454 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRENNAND, KRISTEN JENNIFER · 2013 to 2017
$2.8M
Training the Next Generation of Physician ScientistsT35AI089693 · NIAID · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI Mark Daniel Hicar · 2011 to 2026
$689k
NIAID NIH HHS T35 AI089693NIMH NIH HHS R01 MH101454NIMH NIH HHS R01 MH106056
6 · The paper itself

Abstract

Studies of induced pluripotent stem cells (iPSCs) from schizophrenia patients and control individuals revealed that the disorder is programmed at the preneuronal stage, involves a common dysregulated mRNA transcriptome, and identified Integrative Nuclear FGFR1 Signaling a common dysregulated mechanism. We used human embryonic stem cell (hESC) and iPSC-derived cerebral organoids from four controls and three schizophrenia patients to model the first trimester of in utero brain development. The schizophrenia organoids revealed an abnormal scattering of proliferating Ki67+ neural progenitor cells (NPCs) from the ventricular zone (VZ), throughout the intermediate (IZ) and cortical (CZ) zones. TBR1 pioneer neurons and reelin, which guides cortico-petal migration, were restricted from the schizophrenia cortex. The maturing neurons were abundantly developed in the subcortical regions, but were depleted from the schizophrenia cortex. The decreased intracortical connectivity was denoted by changes in the orientation and morphology of calretinin interneurons. In schizophrenia organoids, nuclear (n)FGFR1 was abundantly expressed by developing subcortical cells, but was depleted from the neuronal committed cells (NCCs) of the CZ. Transfection of dominant negative and constitutively active nFGFR1 caused widespread disruption of the neuro-ontogenic gene networks in hESC-derived NPCs and NCCs. The fgfr1 gene was the most prominent FGFR gene expressed in NPCs and NCCs, and blocking with PD173074 reproduced both the loss of nFGFR1 and cortical neuronal maturation in hESC cerebral organoids. We report for the first time, progression of the cortical malformation in schizophrenia and link it to altered FGFR1 signaling. Targeting INFS may offer a preventive treatment of schizophrenia.

Indexed as

Calbindin 2Cerebral CortexEmbryonic Stem CellsHumansInterneuronsReceptor, Fibroblast Growth Factor, Type 1Reelin ProteinSchizophreniaCalbindin 2FGFR1 protein, humanReceptor, Fibroblast Growth Factor, Type 1Reelin ProteinRELN protein, human

Identifiers

PMID30446636
PMCPMC5802550
OpenAlexW2769649226

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.