{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:15:51Z","timestamp":1783937751972,"version":"3.55.0"},"reference-count":96,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a systematic review to evaluate cumulative data obtained by Proton Magnetic Resonance Spectroscopic (1H MRS) studies. (2) Methods: A computer-based literature search of Medline, EMBASE, PsycInfo, and ProQuest was performed. Only cross-sectional studies using 1H MRS techniques in participants with SAD and healthy controls (HCs) were selected. (3) Results: The search generated eight studies. The results indicated regional abnormalities in the \u2018fear neurocircuitry\u2019 in patients with SAD. The implicated regions included the anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), insula, occipital cortex (OC), as well as the subcortical regions, including the thalamus, caudate, and the putamen. (4) Conclusions: The evidence derived from eight studies suggests that possible pathophysiological mechanisms of SAD include impairments in the integrity and function of neurons and glial cells, including disturbances in energy metabolism, maintenance of phospholipid membranes, dysregulations of second messenger systems, and excitatory\/inhibitory neurocircuitry. Conducting more cross-sectional studies with larger sample sizes is warranted given the limited evidence in this area of research.<\/jats:p>","DOI":"10.3390\/ijms23094754","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T11:45:55Z","timestamp":1650973555000},"page":"4754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Neurochemical Alterations in Social Anxiety Disorder (SAD): A Systematic Review of Proton Magnetic Resonance Spectroscopic Studies"],"prefix":"10.3390","volume":"23","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 M5S 2S1, Canada"},{"name":"Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafna S.","family":"Rubin-Kahana","sequence":"additional","affiliation":[{"name":"Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5S 2S1, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada"}],"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, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada"},{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney H.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Centre for Depression and Suicide Studies, Unity Health Toronto, Toronto, ON M5B 1M4, Canada"},{"name":"Li Ka Shing Knowledge Institute, Toronto, ON M5B 1T8, Canada"},{"name":"Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, Canada"},{"name":"Homewood Research Institute, Guelph, ON N1E 6K9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6532-911X","authenticated-orcid":false,"given":"Sofia","family":"Chavez","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada"},{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, 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 M5S 2S1, Canada"},{"name":"Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada"},{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Departments of Family and Community Medicine, University of Toronto, Toronto, ON M5T 1R8, Canada"},{"name":"Addictions Division, Centre for Addiction and Mental Health, Toronto, ON M6J 1H3, Canada"},{"name":"Waypoint Research Institute, Waypoint Centre for Mental Health Care, Penetanguishene, ON L9M 1G3, 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