ArticleBiological psychiatry2015
Altered glutamate protein co-expression network topology linked to spine loss in the auditory cortex of schizophrenia.
Article in Biological psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled 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.
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
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials.Molecular psychiatry · 2015Pooled it
- Zebrafish screen of schizophrenia risk genes reveals convergent dysregulation of cholesterol metabolism.bioRxiv : the preprint server for biology · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- Review
- Age-related loss of large dendritic spines in the precuneus is statistically mediated by proteins which are predicted targets of existing drugs.Molecular psychiatry · 2025Article
- Implications of SNP-triggered miRNA dysregulation in Schizophrenia development.Frontiers in genetics · 2024Review
- Dysregulation of Synaptic Plasticity Markers in Schizophrenia.Indian journal of clinical biochemistry : IJCB · 2023Review
- Neurogenetics of Dynamic Connectivity Patterns Associated With Obsessive-Compulsive Symptoms in Healthy Children.Biological psychiatry global open science · 2022Article
- MAP2 is differentially phosphorylated in schizophrenia, altering its function.Molecular psychiatry · 2021Article
- Review
- Weighted gene co-expression network analysis identifiesAnnals of translational medicine · 2020Article
- Long non-coding RNA Neat1 regulates adaptive behavioural response to stress in mice.Translational psychiatry · 2020Article
- Missense variants in ATP1A3 and FXYD gene family are associated with childhood-onset schizophrenia.Molecular psychiatry · 2020Article
- Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes.Scientific reports · 2020Article
- Synaptic Plasticity Shapes Brain Connectivity: Implications for Network Topology.International journal of molecular sciences · 2019Review
- Identifying genuine protein-protein interactions within communities of gene co-expression networks using a deconvolution method.IET systems biology · 2019Article
- Inefficient neural system stabilization: a theory of spontaneous resolutions and recurrent relapses in psychosisJournal of psychiatry & neuroscience : JPN · 2019Review
- mGAP: the macaque genotype and phenotype resource, a framework for accessing and interpreting macaque variant data, and identifying new models of human disease.BMC genomics · 2019Article
- Laser capture microdissection-targeted mass spectrometry: a method for multiplexed protein quantification within individual layers of the cerebral cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
Corrections and comments
- Commented on by
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundImpaired glutamatergic signaling is believed to underlie auditory cortex pyramidal neuron dendritic spine loss and auditory symptoms in schizophrenia. Many schizophrenia risk loci converge on the synaptic glutamate signaling network. We therefore hypothesized that alterations in glutamate signaling protein expression and co-expression network features are present in schizophrenia.
methodsGray matter homogenates were prepared from auditory cortex gray matter of 22 schizophrenia and 23 matched control subjects, a subset of whom had been previously assessed for dendritic spine density. One hundred fifty-five selected synaptic proteins were quantified by targeted mass spectrometry. Protein co-expression networks were constructed using weighted gene co-expression network analysis.
resultsProteins with evidence for altered expression in schizophrenia were significantly enriched for glutamate signaling pathway proteins (GRIA4, GRIA3, ATP1A3, and GNAQ). Synaptic protein co-expression was significantly decreased in schizophrenia with the exception of a small group of postsynaptic density proteins, whose co-expression increased and inversely correlated with spine density in schizophrenia subjects.
conclusionsWe observed alterations in the expression of glutamate signaling pathway proteins. Among these, the novel observation of reduced ATP1A3 expression is supported by strong genetic evidence indicating it may contribute to psychosis and cognitive impairment phenotypes. The observations of altered protein network topology further highlight the complexity of glutamate signaling network pathology in schizophrenia and provide a framework for evaluating future experiments to model the contribution of genetic risk to disease pathology.
Indexed as
Identifiers
What OpenQuestion holds
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.