ArticleThe American journal of psychiatry2015
Synaptic proteins in the hippocampus indicative of increased neuronal activity in CA3 in schizophrenia.
Article in The American journal of psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Synapse Pathology in Schizophrenia: A Meta-analysis of Postsynaptic Elements in Postmortem Brain Studies.Schizophrenia bulletin · 2020Pooled it
- Schizophrenia.Nature reviews. Disease primers · 2025Review
- Hippocampal subfield activity in schizophrenia: Effects of the disease course.Schizophrenia research · 2025Article
- Pharmacological reduction of reverse-translated hippocampal hyperactivity in mouse: relevance for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Schizophrenia pathology reverse-translated into mouse shows hippocampal hyperactivity, psychosis behaviors and hyper-synchronous events.Molecular psychiatry · 2025Article
- Impaired Hippocampal Circuitry and Memory Dysfunction in Schizophrenia.Nature. Mental health · 2025Article
- Article
- Autophagy defects at weaning impair complement-dependent synaptic pruning and induce behavior deficits.Journal of neuroinflammation · 2024Article
- Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment.Brain sciences · 2023Review
- Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia.Antioxidants (Basel, Switzerland) · 2022Review
- Relevance of interactions between dopamine and glutamate neurotransmission in schizophrenia.Molecular psychiatry · 2022Review
- Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models.International journal of molecular sciences · 2022Review
- Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis.Nature genetics · 2022Article
- The shallow cognitive map hypothesis: A hippocampal framework for thought disorder in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2022Review
- Distinct contributions of GluA1-containing AMPA receptors of different hippocampal subfields to salience processing, memory and impulse control.Translational psychiatry · 2022Article
- 16p13.11 deletion variants associated with neuropsychiatric disorders cause morphological and synaptic changes in induced pluripotent stem cell-derived neurons.Frontiers in psychiatry · 2022Article
- Mnemonic Discrimination Deficits in First-Episode Psychosis and a Ketamine Model Suggest Dentate Gyrus Pathology Linked to NMDA Receptor Hypofunction.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2021Article
- Linking proteomic alterations in schizophrenia hippocampus to NMDAr hypofunction in human neurons and oligodendrocytes.European archives of psychiatry and clinical neuroscience · 2021Article
- A Diagnosis and Biotype Comparison Across the Psychosis Spectrum: Investigating Volume and Shape Amygdala-Hippocampal Differences from the B-SNIP Study.Schizophrenia bulletin · 2021Article
Corrections and comments
- Commented on by
- Erratum issuedCorrection.2015
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveIn schizophrenia, hippocampal perfusion is increased and declarative memory function is degraded. Based on an a priori model of hippocampal dysfunction in schizophrenic psychosis, the authors postulated molecular and cellular changes in CA3 consistent with increased NMDA receptor signaling.
methodPostmortem hippocampal subfield tissue (CA3, CA1) from subjects with schizophrenia and nonpsychiatric comparison subjects was analyzed using Western blotting and Golgi histochemistry to examine the hypothesized outcomes.
resultsThe GluN2B-containing NMDA receptors (GluN2B/GluN1) and their associated postsynaptic membrane protein PSD95 were both increased in schizophrenia in CA3 tissue, but not in CA1 tissue. Quantitative analyses of Golgi-stained hippocampal neurons showed an increase in spine density on CA3 pyramidal cell apical dendrites (stratum radiatum) and an increase in the number of thorny excrescences.
conclusionsThe hippocampal data are consistent with increased excitatory signaling in CA3 and/or with an elevation in silent synapses in CA3, a state that may contribute to an increase in long-term potentiation in CA3 with subsequent stimulation and "unsilencing." These changes are plausibly associated with increased associational activity in CA3, with degraded declarative memory function, and with formation of false memories with psychotic content. The influence of these hyperactive hippocampal projections on targets in the limbic neocortex could contribute to components of schizophrenia manifestations in other cerebral regions.
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