ArticleSchizophrenia (Heidelberg, Germany)2022
Machine Learning algorithm unveils glutamatergic alterations in the post-mortem schizophrenia brain.
Article in Schizophrenia (Heidelberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 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
30 citing papers in PubMed, 3 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.Molecular psychiatry · 2023Pooled it
- Pooled it
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- Blood levels of D-aspartate oxidase, D-amino acid oxidase, serine racemase, and pLG72 are influenced by diagnoses of schizophrenia and autism spectrum disorder.Schizophrenia (Heidelberg, Germany) · 2026Article
- Transformer architecture for diagnosing schizophrenia disabilities through EEG analysis.Frontiers in physiology · 2026Article
- Metabotropic Glutamate Receptor-Dependent Synaptic Plasticity in Age-Related Neurodegenerative Disorders.Neural plasticity · 2026Review
- Free D-aspartate modulates the expression of proteins linked to schizophrenia and autism spectrum disorder during early postnatal life.Cellular and molecular life sciences : CMLS · 2025Article
- A novel strategy for enhanced schizophrenia detection using established CNN architectures.BMC medical imaging · 2025Article
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- Transcriptomic and Proteomic Changes in the Brain Along with Increasing Phenotypic Severity in a Rat Model of Neonatal Hyperbilirubinemia.International journal of molecular sciences · 2025Article
- Prenatal Exposure to Lipopolysaccharide or Valproate Leads to Abnormal Accumulation of the NMDA Receptor Agonist D-Aspartate in the Adolescent Rat Brain.Journal of neurochemistry · 2025Article
- The Role of Astrocytes in the Molecular Pathophysiology of Schizophrenia: Between Neurodevelopment and Neurodegeneration.Biomolecules · 2025Review
- Dysregulated Transcript Expression but Not Function of the Glutamate Transporter EAAT2 in the Dorsolateral Prefrontal Cortex in Schizophrenia.Schizophrenia bulletin · 2025Article
- Interpretable machine learning to evaluate relationships between DAO/DAOA (pLG72) protein data and features in clinical assessments, functional outcome, and cognitive function in schizophrenia patients.Schizophrenia (Heidelberg, Germany) · 2025Article
- Variations of blood D-serine and D-aspartate homeostasis track psychosis stages.Schizophrenia (Heidelberg, Germany) · 2024Article
- Addressing brain metabolic connectivity in treatment-resistant schizophrenia: a novel graph theory-driven application ofSchizophrenia (Heidelberg, Germany) · 2024Article
- Exploring the Intersection of Schizophrenia, Machine Learning, and Genomics: Scoping Review.JMIR bioinformatics and biotechnology · 2024Article
- Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization.Molecular psychiatry · 2024Article
- Decreased free D-aspartate levels in the blood serum of patients with schizophrenia.Frontiers in psychiatry · 2024Article
- Schizophrenia diagnosis based on diverse epoch size resting-state EEG using machine learning.PeerJ. Computer science · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
Schizophrenia is a disorder of synaptic plasticity and aberrant connectivity in which a major dysfunction in glutamate synapse has been suggested. However, a multi-level approach tackling diverse clusters of interacting molecules of the glutamate signaling in schizophrenia is still lacking. We investigated in the post-mortem dorsolateral prefrontal cortex (DLPFC) and hippocampus of schizophrenia patients and non-psychiatric controls, the levels of neuroactive D- and L-amino acids (L-glutamate, D-serine, glycine, L-aspartate, D-aspartate) by HPLC. Moreover, by quantitative RT-PCR and western blotting we analyzed, respectively, the mRNA and protein levels of pre- and post-synaptic key molecules involved in the glutamatergic synapse functioning, including glutamate receptors (NMDA, AMPA, metabotropic), their interacting scaffolding proteins (PSD-95, Homer1b/c), plasma membrane and vesicular glutamate transporters (EAAT1, EAAT2, VGluT1, VGluT2), enzymes involved either in glutamate-dependent GABA neurotransmitter synthesis (GAD65 and 67), or in post-synaptic NMDA receptor-mediated signaling (CAMKIIα) and the pre-synaptic marker Synapsin-1. Univariable analyses revealed that none of the investigated molecules was differently represented in the post-mortem DLPFC and hippocampus of schizophrenia patients, compared with controls. Nonetheless, multivariable hypothesis-driven analyses revealed that the presence of schizophrenia was significantly affected by variations in neuroactive amino acid levels and glutamate-related synaptic elements. Furthermore, a Machine Learning hypothesis-free unveiled other discriminative clusters of molecules, one in the DLPFC and another in the hippocampus. Overall, while confirming a key role of glutamatergic synapse in the molecular pathophysiology of schizophrenia, we reported molecular signatures encompassing elements of the glutamate synapse able to discriminate patients with schizophrenia and normal individuals.
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.