{"doi":"10.1016/j.bpsgos.2025.100606","title":"Cortical GABAergic Neuron Dysregulation in Schizophrenia Is Age Dependent","abstract":"Background: Cortical GABAergic (gamma-aminobutyric acidergic) neuron dysregulation is implicated in schizophrenia (SCZ), but it remains unclear whether these changes are due to altered cell proportions or per-cell changes in messenger RNA (mRNA) expression. Methods: We analyzed 14 bulk and cell type-specific RNA sequencing (RNA-seq) datasets from 1408 individuals (672 SCZ cases, 736 controls) across 3 neocortical regions. We deconvolved GABAergic cell-subtype proportions from bulk RNA-seq and benchmarked them against single-nucleus RNA-seq and stereological densities from matched donors. We assessed SCZ- and age-associated changes in cell proportions and per-cell gene expression. Results: SCZ was associated with altered proportions of neocortical parvalbumin (PVALB) and somatostatin (SST) cells, depending on the subject's age at death. Younger SCZ cases (age < 70 years) showed reduced PVALB and SST cell proportions, while older cases showed unchanged or increased proportions compared with controls. Earlier-onset SCZ, associated with more severe clinical symptoms, was linked to greater reductions in these cell types. Additionally, there was robust evidence for reduced per-cell SST and vasoactive intestinal peptide mRNA among younger cases with SCZ. Conclusions: These findings suggest that SCZ is associated with complex, age-dependent alterations in GABAergic neurons, particularly affecting PVALB and SST cells. Our study underscores the importance of age-stratified analyses in SCZ, suggesting that distinct pathological processes underlie GABAergic neuron dysregulation across different age and symptom-severity groups and warranting tailored therapeutic approaches.","journal":"Biological Psychiatry Global Open Science","year":2025,"id":528804,"datarank":0.1717606525940067,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.006968809293790248,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.006968809293790248,"corpus_percentile":33.03163920476522,"corpus_rank":8658,"citation_count":2,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.55,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1407096,"name":"Xiaolin Zhou","orcid":"0000-0001-7363-4360","position":1,"is_corresponding":false},{"id":1407549,"name":"Nicole Endresz","orcid":null,"position":2,"is_corresponding":false},{"id":741392,"name":"Keon Arbabi","orcid":"0000-0003-3219-8835","position":3,"is_corresponding":false},{"id":1407097,"name":"Àlex G. Segura","orcid":"0000-0002-9398-2183","position":4,"is_corresponding":false},{"id":355527,"name":"Daniel Felsky","orcid":"0000-0003-1831-9848","position":5,"is_corresponding":false},{"id":985743,"name":"Andreea O. Diaconescu","orcid":"0000-0002-3633-9757","position":6,"is_corresponding":false},{"id":49663,"name":"Etienne Sibille","orcid":"0000-0001-5832-6570","position":7,"is_corresponding":false},{"id":560534,"name":"Shreejoy J. Tripathy","orcid":"0000-0002-1007-9061","position":8,"is_corresponding":false},{"id":1407548,"name":"Daniel Kiss","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:50:52.565868Z","pmid":"41159096","pmcid":"PMC12556227","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":[]}