ArticleBiological psychiatry2023
Laminar-Specific Alterations in Calbindin-Positive Boutons in the Prefrontal Cortex of Subjects With Schizophrenia.
Article in Biological psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 4 citations in OpenAlex.
- Transcriptional Profiles of Somatostatin and Parvalbumin Interneuron Subtypes in the Human Dorsolateral Prefrontal Cortex: Implications for Schizophrenia.The American journal of psychiatry · 2026Article
- Visual suppression deficits as a biomarker of working memory impairment in schizophrenia.Schizophrenia research. Cognition · 2026Review
- Alterations in Prefrontal Cortical Somatostatin Neurons in Schizophrenia: Evidence for Weaker Inhibition of Pyramidal Neuron Dendrites.Biological psychiatry · 2025Article
- Metabolic syndrome in patients with schizophrenia: Underlying mechanisms and therapeutic approaches (Review).Molecular medicine reports · 2025Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCognitive deficits in schizophrenia are associated with altered GABA (gamma-aminobutyric acid) neurotransmission in the prefrontal cortex (PFC). GABA neurotransmission requires GABA synthesis by 2 isoforms of glutamic acid decarboxylase (GAD65 and GAD67) and packaging by the vesicular GABA transporter (vGAT). Current postmortem findings suggest that GAD67 messenger RNA is lower in a subset of the calbindin-expressing (CB+) class of GABA neurons in schizophrenia. Hence, we assessed if CB+ GABA neuron boutons are affected in schizophrenia.
methodsFor 20 matched pairs of subjects with schizophrenia and unaffected comparison subjects, PFC tissue sections were immunolabeled for vGAT, CB, GAD67, and GAD65. The density of CB+ GABA boutons and levels of the 4 proteins per bouton were quantified.
resultsSome CB+ GABA boutons contained both GAD65 and GAD67 (GAD65+/GAD67+), whereas others contained only GAD65 (GAD65+) or GAD67 (GAD67+). In schizophrenia, vGAT+/CB+/GAD65+/GAD67+ bouton density was not altered, vGAT+/CB+/GAD65+ bouton density was 86% higher in layers 2/superficial 3 (L2/3s), and vGAT+/CB+/GAD67+ bouton density was 36% lower in L5-6. Bouton GAD levels were differentially altered across bouton types and layers. In schizophrenia, the sum of GAD65 and GAD67 levels in vGAT+/CB+/GAD65+/GAD67+ boutons was 36% lower in L6, GAD65 levels were 51% higher in vGAT+/CB+/GAD65+ boutons in L2, and GAD67 levels in vGAT+/CB+/GAD67+ boutons were 30% to 46% lower in L2/3s-6.
conclusionsThese findings indicate that schizophrenia-associated alterations in the strength of inhibition from CB+ GABA neurons in the PFC differ across cortical layers and bouton classes, suggesting complex contributions to PFC dysfunction and cognitive impairments in schizophrenia.
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