{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T15:11:04Z","timestamp":1771168264082,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["PCN Reports"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Schizophrenia spectrum disorders (SSDs) and autism spectrum disorder (ASD) share social\u2010cognitive deficits, genetic architecture, and overlapping animal models, yet the neurochemical signatures that differentiate them remain unclear. This protocol describes a systematic review and meta\u2010analysis of proton magnetic resonance spectroscopy (\n                      <jats:sup>1<\/jats:sup>\n                      H\u2010MRS) studies examining glutamate, glutamine, and their combined signals. The primary aim is to establish a human neurochemical benchmark to guide translational research.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eligible studies will be those measuring\n                      <jats:sup>1<\/jats:sup>\n                      H\u2010MRS glutamatergic metabolites at \u22653\u2009T field strength in at least one of five brain regions: anterior cingulate cortex, dorsolateral prefrontal cortex, hippocampus, striatum, or thalamus. Adults (\u226518 years) with SSD (stratified as ultra\u2010high risk, first\u2010episode psychosis, and treatment\u2010resistant schizophrenia) and ASD diagnosed using standardized criteria will be compared to healthy controls. Systematic searches will be conducted in databases. Two independent reviewers will assess the risk of bias using the AXIS (Appraisal Tool for Cross\u2010Sectional Studies) and MRS\u2010Q (Magnetic Resonance Spectroscopy Quality Assessment Tool). Primary outcomes will be regional differences in metabolite concentrations. We will conduct random\u2010effects meta\u2010analyses integrating direct and indirect comparisons, with subgroup analyses by illness stage and medication status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We expect to identify both shared and distinct glutamatergic alterations across SSD subgroups and ASD, with potential stage\u2010specific patterns in cortical and subcortical regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This comprehensive analysis aims to identify regional brain glutamatergic biomarkers differentiating SSD and ASD. These neurochemical signatures will provide an essential reference framework for validating and guiding reverse\u2010translational research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO Registration Number<\/jats:title>\n                    <jats:p>CRD420251003550.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pcn5.70260","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T14:36:52Z","timestamp":1764686212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Meta\u2010analysis of\n                    <sup>1<\/sup>\n                    H\u2010MRS glutamate profiles in adult schizophrenia spectrum disorders and autism spectrum disorder: Study protocol"],"prefix":"10.1002","volume":"4","author":[{"given":"Yusuke","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry Graduate School of Medicine The University of Tokyo Bunkyo\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1704-6411","authenticated-orcid":false,"given":"Naoki","family":"Takamatsu","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Graduate School of Medicine The University of Tokyo Bunkyo\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-2758","authenticated-orcid":false,"given":"Naohiro","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Graduate School of Medicine The University of Tokyo Bunkyo\u2010ku Tokyo Japan"},{"name":"International Research Center for Neurointelligence (IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS) The University of Tokyo Bunkyo\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sho","family":"Yagishita","sequence":"additional","affiliation":[{"name":"Department of Structural Physiology Graduate School of Medicine, Center for Disease Biology and Integrative Medicine The University of Tokyo Bunkyo\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoto","family":"Kasai","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Graduate School of Medicine The University of Tokyo Bunkyo\u2010ku Tokyo Japan"},{"name":"International Research Center for Neurointelligence (IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS) The University of Tokyo Bunkyo\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2020.3908"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-020-04408-4"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2024.1381526"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.12.013"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbae202"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.16m11422"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbae044"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01072-5"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12803"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01386.x"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23115968"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04556-w"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04434-5"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.12.129"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-01991-7"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2016.0442"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01297-6"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02382-8"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbr069"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2020.111080"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2024.105728"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02079-y"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g7647"},{"key":"e_1_2_15_25_1","unstructured":"HigginsJ WelchV. 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