{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:03:29Z","timestamp":1792789409059,"version":"4.5.0"},"reference-count":106,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mitacs Canopy Grant","award":["IT12914"],"award-info":[{"award-number":["IT12914"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations. Considering the reduced availability of conventional therapies, we aimed to improve our understanding of the biological mechanisms in SAD by evaluating gamma-aminobutyric acid (GABA) and other neurometabolites (including glutamate + glutamine\/glutamix (Glx), N-acetyl aspartate (NAA), myo-inositol (mI), total choline (tCho), and total creatine (tCr) in the dorsomedial prefrontal cortex\/anterior cingulate cortex (dmPFC\/ACC), dorsolateral prefrontal cortex (dlPFC), and the insula). In this pilot study, we recruited 26 (age: 25.3 \u00b1 5.0 years; 61.5% female) individuals with SAD and 26 (age: 25.1 \u00b1 4.4 years; 61.5% female) sex-age-matched controls. Using proton magnetic resonance spectroscopy, we found that compared to the controls, GABA+ macromolecular signal (GABA+) in dlPFC (t = 2.63; p = 0.012) and Glx in the insula (Mann\u2013Whitney U = 178.3; p = 0.024) were higher in the participants with SAD. However, no between-group differences were observed in dmPFC\/ACC (t = 0.39; p = 0.699). Increased GABA+ in dlPFC could be explained by aberrant GABA transporters. In the insula, increased Glx may be associated with the dysfunction of glutamate transporters or decreased activity of glutamic acid decarboxylase in the GABAergic inhibitory neurons. However, these proposed mechanisms need to be further investigated in SAD.<\/jats:p>","DOI":"10.3390\/ijms26146915","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T13:33:27Z","timestamp":1752845607000},"page":"6915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Proton Magnetic Resonance Spectroscopy (1H MRS) Pilot Study Revealing Altered Glutamatergic and Gamma-Aminobutyric Acid (GABA)ergic Neurotransmission in Social Anxiety Disorder (SAD)"],"prefix":"10.3390","volume":"26","author":[{"given":"Sonja","family":"Elsaid","sequence":"first","affiliation":[{"name":"Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M6J 1H4, Canada"},{"name":"Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Brain Health Imaging Centre (BHIC), Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6838-4114","authenticated-orcid":false,"given":"Stefan","family":"Kloiber","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Brain Health Imaging Centre (BHIC), Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M6J 1H4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0626-9310","authenticated-orcid":false,"given":"Kimberly L.","family":"Desmond","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Brain Health Imaging Centre (BHIC), Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6406-4973","authenticated-orcid":false,"given":"Bernard","family":"Le Foll","sequence":"additional","affiliation":[{"name":"Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M6J 1H4, Canada"},{"name":"Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Brain Health Imaging Centre (BHIC), Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA"},{"name":"Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M6J 1H4, Canada"},{"name":"Addictions Division, Centre for Addiction and Mental Health, Toronto, ON M6J 1H4, Canada"},{"name":"Department of Family and Community Medicine, University of Toronto, Toronto, ON M5G 1V7, Canada"},{"name":"Waypoint Research Institute, Waypoint Centre for Mental Health Care, Penetanguishene, ON L9M 1G3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1001\/archpsyc.62.6.593","article-title":"Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication","volume":"62","author":"Kessler","year":"2005","journal-title":"Arch. 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