ArticleThe American journal of psychiatry2017
Selective Loss of Smaller Spines in Schizophrenia.
Article in The American journal of psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Synapse Pathology in Schizophrenia: A Meta-analysis of Postsynaptic Elements in Postmortem Brain Studies.Schizophrenia bulletin · 2020Pooled it
- Accelerated aging in schizophrenia: integrating epigenetic clocks, telomere dynamics, senescence-associated secretory phenotype, and oxidative stress.European archives of psychiatry and clinical neuroscience · 2026Review
- Article
- Functional genomic profiling of schizophrenia-associated genes reveals key microglial regulators.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- Synaptic dysfunction and adaptation after NMDA receptor ablation in the mouse medial prefrontal cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Schizophrenia-Related Synaptic Dysfunction and Abnormal Sensorimotor Gating in Akap11-Deficient Mice.Schizophrenia bulletin · 2026Article
- Peripheral complement C3 and C4 are associated with clinical features of schizophrenia.Frontiers in psychiatry · 2026Article
- Can Sodium Oxybate Mitigate the Symptoms of Schizophrenia?Current neuropharmacology · 2026Review
- Functional Genomic Profiling of Schizophrenia-Associated Genes Reveals Key Microglial Regulators.bioRxiv : the preprint server for biology · 2025Article
- Altered Molecular Composition of a Specific Subset of Prefrontal Cortical Excitatory Synapses in Schizophrenia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- AUGMENTED DOUBLY ROBUST POST-IMPUTATION INFERENCE FOR PROTEOMIC DATA.The annals of applied statistics · 2025Article
- 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
- AUGMENTED DOUBLY ROBUST POST-IMPUTATION INFERENCE FOR PROTEOMIC DATA.bioRxiv : the preprint server for biology · 2025Article
- Neuronal Synaptic Communication and Mitochondrial Energetics in Human Health and Disease.Advances in experimental medicine and biology · 2025Review
- Impacts of CACNB4 overexpression on dendritic spine density in both sexes and relevance to schizophrenia.Translational psychiatry · 2024Article
- Ancestral retrovirus envelope protein ERVWE1 upregulates circ_0001810, a potential biomarker for schizophrenia, and induces neuronal mitochondrial dysfunction via activating AK2.Cell & bioscience · 2024Article
- Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review.Schizophrenia research · 2024Review
- Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.Molecular biology reports · 2024Review
- Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
objectiveDecreased density of dendritic spines in adult schizophrenia subjects has been hypothesized to result from increased pruning of excess synapses in adolescence. In vivo imaging studies have confirmed that synaptic pruning is largely driven by the loss of large or mature synapses. Thus, increased pruning throughout adolescence would likely result in a deficit of large spines in adulthood. Here, the authors examined the density and volume of dendritic spines in deep layer 3 of the auditory cortex of 20 schizophrenia and 20 matched comparison subjects as well as aberrant voltage-gated calcium channel subunit protein expression linked to spine loss.
methodPrimary auditory cortex deep layer 3 spine density and volume was assessed in 20 pairs of schizophrenia and matched comparison subjects in an initial and replication cohort (12 and eight pairs) by immunohistochemistry-confocal microscopy. Targeted mass spectrometry was used to quantify postsynaptic density and voltage-gated calcium channel protein expression. The effect of increased voltage-gated calcium channel subunit protein expression on spine density and volume was assessed in primary rat neuronal culture.
resultsOnly the smallest spines are lost in deep layer 3 of the primary auditory cortex in subjects with schizophrenia, while larger spines are retained. Levels of the tryptic peptide ALFDFLK, found in the schizophrenia risk gene CACNB4, are inversely correlated with the density of smaller, but not larger, spines in schizophrenia subjects. Consistent with this observation, CACNB4 overexpression resulted in a lower density of smaller spines in primary neuronal cultures.
conclusionsThese findings require a rethinking of the overpruning hypothesis, demonstrate a link between small spine loss and a schizophrenia risk gene, and should spur more in-depth investigations of the mechanisms that govern new or small spine generation and stabilization under normal conditions as well as how this process is impaired in schizophrenia.
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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.