{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:25:34Z","timestamp":1790637934743,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ketamine has emerged as a highly effective intervention for treatment\u2010resistant depression (TRD). Though it acts as a non\u2010competitive antagonist of excitatory N\u2010methyl\u2010D\u2010aspartate receptors (NMDAR), widely expressed in the brain, including on inhibitory \u03b3\u2010aminobutyric acid (GABA)\u2010ergic 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 (\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010MRS) to measure both glutamate and GABA levels in the dorsal anterior cingulate cortex (dACC) in 60 participants with TRD before (~within 1\u2009week), and 24\u2009h after a 40\u2010min intravenous infusion with 0.5\u2009mg\/kg of racemic (\n                    <jats:italic>R,S<\/jats:italic>\n                    )\u2010ketamine. The 17\u2010item Hamilton Depression Rating Scale (HDRS\n                    <jats:sub>17<\/jats:sub>\n                    ) was used as the primary measure of clinical improvement, and a 50% or greater improvement in HDRS\n                    <jats:sub>17<\/jats:sub>\n                    ratings was used to define treatment responders. Ketamine increased mean dACC glutamate levels in responders only 24 h after treatment (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200925,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01). Further, lower glutamate levels at baseline predicted greater improvements in HDRS\n                    <jats:sub>17<\/jats:sub>\n                    scores at 24\u2009h post treatment (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). However, GABA levels remained stable after treatment irrespective of response status (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.90). Metabolites associated with neuronal integrity (tNAA), metabolic function (tCr), and membrane turnover (tCho), which may serve as complementary biological evidence of ketamine\u2010induced plasticity, also increased with treatment (all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). Results provide evidence of sustained enhancements of neurotransmission or other glutamate\u2010related metabolic effects following subanesthetic ketamine in responders and a potential role of ACC glutamate levels as a biomarker of responsivity to ketamine.\n                  <\/jats:p>","DOI":"10.1002\/jnr.70102","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:27:16Z","timestamp":1767176836000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Modulation of Magnetic Resonance Spectroscopy Levels of Glutamate and GABA by Ketamine in Treatment\u2010Resistant Depression"],"prefix":"10.1002","volume":"104","author":[{"given":"Stephanie","family":"Njau","sequence":"first","affiliation":[{"name":"Department of Neurology, Ahmanson\u2010Lovelace Brain Mapping Center Geffen School of Medicine at the University of California, Los Angeles  Los Angeles California 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Medicine at the University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"O'Neill","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior Geffen School of Medicine at the University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woods P.","family":"Roger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ahmanson\u2010Lovelace Brain Mapping Center Geffen School of Medicine at the University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane","family":"Norris","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human 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