{"doi":"10.1002/jnr.70102","title":"Modulation of Magnetic Resonance Spectroscopy Levels of Glutamate and GABA by Ketamine in Treatment‐Resistant Depression","abstract":"ABSTRACT Ketamine has emerged as a highly effective intervention for treatment‐resistant depression (TRD). Though it acts as a non‐competitive antagonist of excitatory N‐methyl‐D‐aspartate receptors (NMDAR), widely expressed in the brain, including on inhibitory γ‐aminobutyric acid (GABA)‐ergic cells, the mechanisms of its antidepressant action are less clear. To investigate the links between glutamate and GABA neurotransmission and the clinical benefits of ketamine, we used proton magnetic resonance spectroscopy ( 1 H‐MRS) to measure both glutamate and GABA levels in the dorsal anterior cingulate cortex (dACC) in 60 participants with TRD before (~within 1 week), and 24 h after a 40‐min intravenous infusion with 0.5 mg/kg of racemic ( R,S )‐ketamine. The 17‐item Hamilton Depression Rating Scale (HDRS 17 ) was used as the primary measure of clinical improvement, and a 50% or greater improvement in HDRS 17 ratings was used to define treatment responders. Ketamine increased mean dACC glutamate levels in responders only 24 h after treatment ( n = 25, p = 0.01). Further, lower glutamate levels at baseline predicted greater improvements in HDRS 17 scores at 24 h post treatment ( p < 0.0001). However, GABA levels remained stable after treatment irrespective of response status ( p = 0.90). Metabolites associated with neuronal integrity (tNAA), metabolic function (tCr), and membrane turnover (tCho), which may serve as complementary biological evidence of ketamine‐induced plasticity, also increased with treatment (all p < 0.01). Results provide evidence of sustained enhancements of neurotransmission or other glutamate‐related metabolic effects following subanesthetic ketamine in responders and a potential role of ACC glutamate levels as a biomarker of responsivity to ketamine.","journal":"Journal of Neuroscience Research","year":2025,"id":587506,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":275661,"name":"Artemis Zavaliangos‐Petropulu","orcid":"0000-0003-1953-8663","position":1,"is_corresponding":false},{"id":724319,"name":"Shantanu H. Joshi","orcid":"0000-0003-1287-7005","position":2,"is_corresponding":false},{"id":341775,"name":"John O. Brooks","orcid":"0000-0001-5420-7208","position":3,"is_corresponding":false},{"id":1503491,"name":"Joseph O'Neill","orcid":null,"position":4,"is_corresponding":false},{"id":1503492,"name":"W. H. Savage Roger","orcid":null,"position":5,"is_corresponding":false},{"id":1376581,"name":"Vera Norris","orcid":null,"position":6,"is_corresponding":false},{"id":1503493,"name":"Randall T. Espinoza","orcid":null,"position":7,"is_corresponding":false},{"id":314811,"name":"Katherine L. Narr","orcid":"0000-0002-9396-7936","position":8,"is_corresponding":false},{"id":420146,"name":"Stephanie Njau","orcid":"0000-0002-0662-6149","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:59:39.958043Z","pmid":"41473990","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":[]}