Evidence map›Paper›PMID 28348379›Full record

ReviewMolecular psychiatry2017

Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.

A Devor, O A Andreassen, Y Wang, T Mäki-Marttunen, O B Smeland, C-C Fan, A J Schork, D Holland, W K Thompson, A Witoelar and 8 more

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
5.4field-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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

  1. Pooled it
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  13. Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modeling.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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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

18 authors at 9 institutions in 4 countries.

A DevorDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
O A AndreassenNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Y WangDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
T Mäki-MarttunenNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
O B SmelandNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
C-C FanDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
A J SchorkCognitive Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
D HollandDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
W K ThompsonInstitute of Biological Psychiatry, Medical Health Center, Sct. Hans Hospital and University of Copenhagen, Copenhagen, Denmark.
A WitoelarNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
C-H ChenDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
R S DesikanDepartment of Radiology, University of California, San Diego, La Jolla, CA, USA.
L K McEvoyDepartment of Radiology, University of California, San Diego, La Jolla, CA, USA.
S DjurovicDepartment of Medical Genetics, Oslo University Hospital, Oslo, Norway.
P GreengardLaboratory for Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.
P SvenningssonDepartment of Neurology, Karolinska Institute, Stockholm, Sweden.
G T EinevollDepartment of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Oslo, Norway.
A M DaleDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
University of California, San Diego · USUniversity of Oslo · NOOslo University Hospital · NOUniversity of Copenhagen · DKKarolinska Institutet · SENorwegian University of Life Sciences · NORockefeller University · USUniversity of Bergen · NOUniversity of California, San Francisco · US

Funding

Spatiotemporal Brain Imaging: Microscopic &System LevelR01EB000790 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DALE, ANDERS M · 2002 to 2015
$15.3M
MICROSCOPIC FOUNDATION OF MULTIMODAL HUMAN IMAGINGR01MH111359 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DALE, ANDERS M, DEVOR, ANNA · 2016 to 2020
$5.6M
Neuronal, glial and BOLD fMRI signals: From BOLD to 2-photon microscopyR01NS057198 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEVOR, ANNA · 2009 to 2017
$2.6M
Identifying the Polygenic Basis of the Human Brain and Psychiatric DisordersR01MH100351 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, CHI-HUA · 2013 to 2017
$2.1M
Polygenicity, Pleiotrophy and Power: Novel Statistical Methods for Gene DiscoveryR01GM104400 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI THOMPSON, WESLEY KURT · 2014 to 2017
$1.6M
NIBIB NIH HHS R01 EB000790NIGMS NIH HHS R01 GM104400NIMH NIH HHS R01 MH100351NIMH NIH HHS R01 MH111359NINDS NIH HHS R01 NS057198
6 · The paper itself

Abstract

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

Indexed as

BrainDopamineDopamine and cAMP-Regulated Phosphoprotein 32gamma-Aminobutyric AcidGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMultifactorial InheritancePolymorphism, Single NucleotideReceptors, Ionotropic GlutamateReceptors, Metabotropic GlutamateRisk FactorsSchizophreniaSignal TransductionSynaptic TransmissionDopamineDopamine and cAMP-Regulated Phosphoprotein 32gamma-Aminobutyric AcidReceptors, Ionotropic GlutamateReceptors, Metabotropic Glutamate

Identifiers

PMID28348379
PMCPMC5495879
OpenAlexW2597459336

What OpenQuestion holds

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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.