{"doi":"10.1016/j.biopsych.2015.07.022","title":"Markedly Lower Glutamic Acid Decarboxylase 67 Protein Levels in a Subset of Boutons in Schizophrenia","abstract":null,"journal":"Biological Psychiatry","year":2016,"id":634436,"datarank":0.6141516843333151,"base_score":4.0943445622221,"endowment":4.0943445622221,"self_citation_contribution":0.6141516843333151,"citation_network_contribution":0.0,"self_endowment_contribution":0.6141516843333151,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":664762,"name":"David A. Lewis","orcid":"0000-0002-5534-8392","position":1,"is_corresponding":false},{"id":307536,"name":"Kenneth N. Fish","orcid":"0000-0003-1774-3815","position":2,"is_corresponding":false},{"id":930363,"name":"Brad R. Rocco","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Markedly Lower Glutamic Acid Decarboxylase 67 Protein Levels in a Subset of Boutons in Schizophrenia","abstract":"<h4>Background</h4>Convergent findings indicate that cortical gamma-aminobutyric acid (GABA)ergic circuitry is altered in schizophrenia. Postmortem studies have consistently found lower levels of glutamic acid decarboxylase 67 (GAD67) messenger RNA (mRNA) in the prefrontal cortex (PFC) of subjects with schizophrenia. At the cellular level, the density of GABA neurons with detectable levels of GAD67 mRNA is ~30% lower across cortical layers. Knowing how this transcript deficit translates to GAD67 protein levels in axonal boutons is important for understanding the impact it might have on GABA synthesis. In addition, because reductions in GAD67 expression before, but not after, the maturation of GABAergic boutons results in a lower density of GABAergic boutons in mouse cortical cultures, knowing if GABAergic bouton density is altered in schizophrenia would provide insight into the timing of the GAD67 deficit.<h4>Methods</h4>PFC tissue sections from 20 matched pairs of schizophrenia and comparison subjects were immunolabeled for the vesicular GABA transporter (vGAT) and GAD67.<h4>Results</h4>vGAT+ bouton density did not differ between subject groups, consistent with findings that vGAT mRNA levels are unaltered in the illness and confirming that the number of cortical GABAergic boutons is not lower in schizophrenia. In contrast, in schizophrenia subjects, the proportion of vGAT+ boutons with detectable GAD67 levels (vGAT+/GAD67+ boutons) was 16% lower and mean GAD67 levels were 14% lower in the remaining vGAT+/GAD67+ boutons.<h4>Conclusions</h4>Our findings suggest that GABA production is markedly reduced in a subset of boutons in the PFC of schizophrenia subjects and that this reduction likely occurs after the maturation of GABAergic boutons.","is_dataset_classified":null,"base_score":4.0943445622221,"endowment":4.0943445622221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26364548","pmcid":"PMC4744808","openalex_id":"https://openalex.org/W1659737704","authors":[],"funders":[{"funder_name":"NSF","grant_id":"DGE-0549352 to BRR","title":null},{"funder_name":"NIMH","grant_id":"MH096985 to KNF","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"R37 MH043784","title":null},{"funder_name":"NIMH","grant_id":"MH043784 to DAL","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"R01 MH043784","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR000005","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"R01 MH096985","title":null}],"total_grants":7,"fwci":2.4537,"citation_percentile":0.88554879,"influential_citations":0,"citation_trend":[{"year":2015,"count":1},{"year":2016,"count":7},{"year":2017,"count":4},{"year":2018,"count":7},{"year":2019,"count":6},{"year":2020,"count":6},{"year":2021,"count":7},{"year":2022,"count":6},{"year":2023,"count":2},{"year":2024,"count":7},{"year":2025,"count":4},{"year":2026,"count":2}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4744808","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4744808","host_type":"repository"},{"url":"https://doi.org/10.1016/j.biopsych.2015.07.022","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26364548","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC4744808","host_type":"repository"}],"fields_of_study":["Neuroscience and Neuropharmacology Research","Tryptophan and brain disorders","GABA and Rice Research"],"mesh_terms":["Adult","Autopsy","Female","gamma-Aminobutyric Acid","Glutamate Decarboxylase","Humans","Male","Middle Aged","Schizophrenia","Prefrontal Cortex","Presynaptic Terminals","Vesicular Inhibitory Amino Acid Transport Proteins","GABAergic Neurons"],"keywords":["Glutamate decarboxylase","GABAergic","Schizophrenia (object-oriented programming)","Prefrontal cortex","gamma-Aminobutyric acid","Glutamate receptor","Biology","Endocrinology","Messenger RNA","Neuroscience","Internal medicine","Psychology","Enzyme","Biochemistry","Gene","Medicine","Inhibitory postsynaptic potential","Psychiatry","Receptor","Cognition","Development","Gad67","Vgat","Quantitative Microscopy"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T13:39:52.251839Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}