Evidence map›Paper›PMID 36379214›Full record

ArticleNeuron2023

The miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder.

Ho Namkung, Hiroshi Yukitake, Daisuke Fukudome, Brian J Lee, Mengnan Tian, Gianluca Ursini, Atsushi Saito, Shravika Lam, Suvarnambiga Kannan, Rupali Srivastava and 8 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 5% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. The role ofEpigenetics · 2026
    Review
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  20. Genes · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 1 country.

Ho NamkungDepartment of Biomedical Engineering, Baltimore, MD, USA; Department of Psychiatry, Baltimore, MD, USA.
Hiroshi YukitakeDepartment of Psychiatry, Baltimore, MD, USA.
Daisuke FukudomeDepartment of Psychiatry, Baltimore, MD, USA.
Brian J LeeDepartment of Psychiatry, Baltimore, MD, USA.
Mengnan TianDepartment of Neuroscience, Baltimore, MD, USA.
Gianluca UrsiniDepartment of Psychiatry, Baltimore, MD, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Atsushi SaitoDepartment of Psychiatry, Baltimore, MD, USA.
Shravika LamDepartment of Psychiatry, Baltimore, MD, USA; Department of Neuroscience, Baltimore, MD, USA.
Suvarnambiga KannanDepartment of Psychiatry, Baltimore, MD, USA; Department of Mental Health, Baltimore, MD, USA.
Rupali SrivastavaDepartment of Psychiatry, Baltimore, MD, USA.
Minae NiwaDepartment of Psychiatry, Baltimore, MD, USA.
Kamal SharmaDepartment of Psychiatry, Baltimore, MD, USA; Department of Neuroscience, Baltimore, MD, USA.
Peter ZandiDepartment of Psychiatry, Baltimore, MD, USA; Department of Mental Health, Baltimore, MD, USA; Department of Epidemiology, Baltimore, MD, USA.
Hanna Jaaro-PeledDepartment of Psychiatry, Baltimore, MD, USA.
Koko IshizukaDepartment of Psychiatry, Baltimore, MD, USA.
Nilanjan ChatterjeeDepartment of Epidemiology, Baltimore, MD, USA; Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Richard L HuganirDepartment of Psychiatry, Baltimore, MD, USA; Department of Neuroscience, Baltimore, MD, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
Akira SawaDepartment of Biomedical Engineering, Baltimore, MD, USA; Department of Psychiatry, Baltimore, MD, USA; Department of Neuroscience, Baltimore, MD, USA; Department of Pharmacology, Baltimore, MD, USA; Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Mental Health, Baltimore, MD, USA. Electronic address: asawa1@jhmi.edu.
University of Maryland, Baltimore · USMaryland Department of Health · USJohns Hopkins University · USLieber Institute for Brain Development · US

Funding

Project 3P50MH094268 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SAWA, AKIRA · 2011 to 2020
$19.9M
High throughput marker for cognitive deficit: cellular autofluorescenceR01MH107730 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SAWA, AKIRA · 2018 to 2022
$3.0M
DISC1-dependent defects in neural fate, corticogenesis and cognition in psychosisR01MH105660 · NIMH · JOHNS HOPKINS UNIVERSITY · PI ISHIZUKA, KOKO, SAWA, AKIRA · 2014 to 2018
$2.8M
Oxidative stress and schizophrenia: combination of cell biology and brain imagingR01MH092443 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SAWA, AKIRA · 2011 to 2015
$1.8M
NIMH NIH HHS P50 MH094268NIMH NIH HHS R01 MH092443NIMH NIH HHS R01 MH105660NIMH NIH HHS R01 MH107730
6 · The paper itself

Abstract

Schizophrenia (SZ) and bipolar disorder (BP) are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. This study shows the miR-124-3p-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered the upregulation of miR-124-3p in neuronal cells and the postmortem prefrontal cortex from both SZ and BP patients. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissection, we generated a mouse model that upregulates miR-124-3p in the medial prefrontal cortex. We demonstrated that the upregulation of miR-124-3p increases GRIA2-lacking calcium-permeable AMPARs and perturbs AMPAR-mediated excitatory synaptic transmission, leading to deficits in the behavioral dimensions shared between SZ and BP.

Indexed as

Bipolar DisorderMicroRNAsSchizophreniaAnimalsMiceMultifactorial InheritancePrefrontal CortexMicroRNAsMirn124 microRNA, mouseAMPARbipolar disordermiR-124polygenic riskschizophrenia

Identifiers

PMID36379214
PMCPMC10183200
OpenAlexW4308998323

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.