Evidence map›Paper›PMID 36573631›Full record

ArticleSchizophrenia bulletin2023

Erbb4 Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes.

Amanda Kiemes, Maria Elisa Serrano Navacerrada, Eugene Kim, Karen Randall, Camilla Simmons, Loreto Rojo Gonzalez, Marija-Magdalena Petrinovic, David J Lythgoe, Diana Rotaru, Davide Di Censo and 7 more

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

Article in Schizophrenia bulletin, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 27% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Effects of diazepam on hippocampal blood flow in people at clinical high risk for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Trial
  4. Modulation of hippocampal activity in schizophrenia with levetiracetam: a randomized, double-blind, cross-over, placebo-controlled trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Trial
  5. Article
  6. Article
  7. Article
  8. Hippocampal circuit dysfunction in psychosis.Translational psychiatry · 2022
    Review
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

17 authors at 3 institutions in 3 countries.

Amanda KiemesDepartment of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0001-6819-8090
Maria Elisa Serrano NavacerradaDepartment of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Eugene KimDepartment of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Karen RandallDepartment of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Camilla SimmonsDepartment of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Loreto Rojo GonzalezDepartment of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Marija-Magdalena PetrinovicMRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
David J LythgoeDepartment of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Diana RotaruDepartment of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Davide Di CensoDepartment of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Lydiane HirschlerC.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
Emmanuel L BarbierUniv. Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences, Grenoble, France.
Anthony C VernonMRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
James M StoneBrighton and Sussex Medical School, University of Sussex, Brighton, UK.ORCID 0000-0003-3051-0135
Cathy DaviesDepartment of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0003-3011-8643
Diana CashDepartment of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Gemma ModinosDepartment of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-7870-066X
King's College London · GBInserm · FRBrighton and Sussex Medical School · GB

Funding

Medical Research Council MR/N026063/1Medical Research Council MR/W006251/1Wellcome Trust 202397/Z/16/ZWellcome Trust 203148/Z/16/ZWellcome Trust WT203148/Z/16/Z
6 · The paper itself

Abstract

background and hypothesisConverging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice. STUDY

designHere, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n = 12) and their wild-type littermates (Erbb4F/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography.

resultsErbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified.

conclusionsThese findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species.

Indexed as

GlutaminePsychotic DisordersAnimalsHippocampusInterneuronsMiceNeuroimagingParvalbuminsPhenotypeReceptor, ErbB-4Erbb4 protein, mouseGlutamineParvalbuminsReceptor, ErbB-4Erbb4hippocampusinhibitory interneuronsmiceneuroimagingpsychosis

Identifiers

PMID36573631
PMCPMC10154722
OpenAlexW4312212051

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.