{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:47:11Z","timestamp":1790912831599,"version":"4.1.0"},"reference-count":76,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N027078\/1"],"award-info":[{"award-number":["MR\/N027078\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012176","name":"Maudsley Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012176","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["094849\/Z\/10\/Z"],"award-info":[{"award-number":["094849\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018942","name":"Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018942","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009362","name":"South London and Maudsley NHS Foundation Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000764","name":"King\u2019s College London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000764","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019256","name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre","doi-asserted-by":"publisher","award":["BRC1072\/HEI\/EA\/110410"],"award-info":[{"award-number":["BRC1072\/HEI\/EA\/110410"]}],"id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune dysfunction is implicated in the pathophysiology of schizophrenia. The 18\u2005kDa translocator protein (TSPO), expressed by various cell types, including microglia and astrocytes, is widely used as a marker for neuroinflammation and can be quantified in vivo using PET. However, findings from TSPO PET studies in recent-onset psychosis have been inconsistent, and it remains unknown whether TSPO levels can be modified in schizophrenia. We addressed these questions with a baseline case\u2013control comparison of patients with a first-episode psychotic disorder who were symptomatic despite antipsychotic treatment and healthy volunteers, and a longitudinal study testing the effects of natalizumab (a monoclonal antibody previously shown to reduce TSPO levels in neuroinflammatory conditions) on TSPO levels and symptoms in patients.<\/jats:p>\n                  <jats:p>Baseline and 3-month follow-up brain imaging was carried out using 18F-DPA-714 TSPO PET, quantified as the distribution volume ratio (DVR) in total, frontal lobe and temporal lobe grey matter. A total of 103 volunteers (62 patients and 41 healthy controls) received baseline brain imaging, and 47 patients completed follow-up imaging after receiving natalizumab (n = 31) or placebo (n = 16) infusions. Natalizumab was well tolerated, with no serious treatment-related adverse events. The patient group also received clinical assessments with the Positive and Negative Syndrome Scale at baseline and follow-up.<\/jats:p>\n                  <jats:p>At baseline, DVR was significantly higher in patients relative to controls in total (\u03b72 = 0.04) and temporal lobe (\u03b72 = 0.06) grey matter. However, there was no significant change in DVR across these regions following natalizumab or placebo treatment. Mean \u00b1 standard deviation (SD) CSF levels of natalizumab after treatment were 10.7 \u00b1 27.2\u2005ng\/ml, indicating that the monoclonal antibody crossed the blood\u2013brain barrier. Patients receiving natalizumab showed a modest but statistically significant improvement in Positive and Negative Syndrome Scale total scores (mean \u00b1 SD change: \u22123.7 \u00b1 9.1, Cohen\u2019s d = 0.40, P = 0.017), although there was no relationship between change in DVR and change in symptom severity (P &amp;gt; 0.05).<\/jats:p>\n                  <jats:p>These findings are consistent with elevated grey matter TSPO levels in first-episode psychosis relative to healthy controls. Although natalizumab treatment was associated with a modest reduction in symptoms, the absence of corresponding changes in DVR suggests that higher grey matter TSPO might reflect expression by non-microglial cells. The lack of significant changes in the placebo group indicates that it is a stable trait biomarker. Further work is needed to clarify the functional relevance and cellular specificity of TSPO alterations in psychosis. ClinicalTrials.gov: NCT03093064.<\/jats:p>","DOI":"10.1093\/brain\/awaf455","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T12:41:03Z","timestamp":1764506463000},"page":"620-631","source":"Crossref","is-referenced-by-count":4,"title":["Immune alterations in schizophrenia and the effects of a therapeutic antibody: a neuroimaging study"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3531-8006","authenticated-orcid":false,"given":"Yuya","family":"Mizuno","sequence":"first","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London , London SE5 8AF ,","place":["UK"]},{"name":"South London and Maudsley NHS Foundation Trust , London SE5 8AZ ,","place":["UK"]},{"name":"Department of Neuropsychiatry, Keio University School of Medicine , Tokyo 160-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Carreira Figueiredo","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London , London SE5 8AF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6074-2626","authenticated-orcid":false,"given":"Toby","family":"Pillinger","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London , London SE5 8AF ,","place":["UK"]},{"name":"Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital , London W12 0HS ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Hindley","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London , London SE5 8AF ,","place":["UK"]},{"name":"Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo , Oslo 0450 ,","place":["Norway"]},{"name":"Department of Psychiatry, Lovisenberg Diaconal Hospital , Oslo 0456 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Baxter","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London , London SE5 8AF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita","family":"Parmar","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London , London SE5 8AF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London , London SE5 8AF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek G","family":"Donocik","sequence":"additional","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust , London SE5 8AZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Sleep and Brain Plasticity Centre, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London , London SE5 8AF ,","place":["UK"]},{"name":"Sleep Disorders Centre, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust , London SE1 9RT 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& Guys and St Thomas\u2019 NHS Foundation Trust , London SE1 7EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramla","family":"Awais","sequence":"additional","affiliation":[{"name":"Centre for Radiopharmaceutical Chemistry, University College London , London WC1E 6BS ,","place":["UK"]},{"name":"Department of Chemistry, University College London , London WC1H 0AJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6096-7577","authenticated-orcid":false,"given":"Kerstin","family":"Sander","sequence":"additional","affiliation":[{"name":"Centre for Radiopharmaceutical Chemistry, University College London , London WC1E 6BS ,","place":["UK"]},{"name":"Department of Chemistry, University College London , London WC1H 0AJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"\u00c5rstad","sequence":"additional","affiliation":[{"name":"Centre for Radiopharmaceutical Chemistry, University College London , London WC1E 6BS ,","place":["UK"]},{"name":"Department of Chemistry, University College London , London WC1H 0AJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marios","family":"Politis","sequence":"additional","affiliation":[{"name":"Neurodegeneration Imaging Group, University of Exeter Medical School , London W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6102-7272","authenticated-orcid":false,"given":"Julia J","family":"Schubert","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London , London SE5 8AF 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