{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:54:36Z","timestamp":1791618876690,"version":"4.3.4"},"reference-count":123,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008582","name":"McGill University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008582","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss National Foundation","award":["P2SKP3_178175"],"award-info":[{"award-number":["P2SKP3_178175"]}]},{"name":"Swiss National Foundation","award":["105314_140351"],"award-info":[{"award-number":["105314_140351"]}]},{"name":"Swiss National Foundation","award":["10001CL_169783"],"award-info":[{"award-number":["10001CL_169783"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Negative symptoms such as anhedonia and apathy are among the most debilitating manifestations of schizophrenia (SZ). Imaging studies have linked these symptoms to morphometric abnormalities in 2 brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and striatum. Higher negative symptoms are generally associated with reduced OFC thickness, while higher apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment or an underlying phenotypic trait. Here, we use multicentre magnetic resonance imaging data to investigate orbitofrontal-striatal abnormalities across the SZ spectrum from healthy populations with high schizotypy to unmedicated and medicated first-episode psychosis (FEP), and patients with chronic SZ. Putamen, caudate, accumbens volume, and OFC thickness were estimated from T1-weighted images acquired in all 3 diagnostic groups and controls from 4 sites (n = 337). Results were first established in 1 discovery dataset and replicated in 3 independent samples. There was a negative correlation between apathy and putamen\/accumbens volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger putamen volume, which appears to be a consequence of antipsychotic medications. The negative association between reduced OFC thickness and total negative symptoms also appeared to vary along the SZ spectrum, being significant only in FEP patients. In schizotypy, there was increased OFC thickness relative to controls. Our findings suggest that negative symptoms are associated with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of SZ. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to the disease onset.<\/jats:p>","DOI":"10.1093\/schbul\/sbaa169","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T23:26:17Z","timestamp":1602804377000},"page":"849-863","source":"Crossref","is-referenced-by-count":42,"title":["Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9486-1439","authenticated-orcid":false,"given":"Matthias","family":"Kirschner","sequence":"first","affiliation":[{"name":"Montreal Neurological Institute, McGill University, Montreal, QC, Canada"},{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6055-8397","authenticated-orcid":false,"given":"Andr\u00e9","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry (UPK), University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benazir","family":"Hodzic-Santor","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Burrer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Manoliu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland"},{"name":"Wellcome Centre for Human Neuroimaging, University College London, London, UK"},{"name":"Max Planck University College London Centre for Computational Psychiatry and Ageing Research, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-5811","authenticated-orcid":false,"given":"Yashar","family":"Zeighami","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6095-7205","authenticated-orcid":false,"given":"Yvonne","family":"Yau","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7980-8667","authenticated-orcid":false,"given":"Nooshin","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Maatz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Habermeyer","sequence":"additional","affiliation":[{"name":"Psychiatric Services Aargau, Brugg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aslan","family":"Abivardi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2171-8313","authenticated-orcid":false,"given":"Mihai","family":"Avram","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology and TUM-NIC Neuroimaging Center, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"},{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Schleswig Holstein University Hospital, University L\u00fcbeck, L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Brandl","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and TUM-NIC Neuroimaging Center, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Sorg","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology and TUM-NIC Neuroimaging Center, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"},{"name":"Department of Psychiatry and TUM-NIC Neuroimaging Center, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9034-148X","authenticated-orcid":false,"given":"Philipp","family":"Homan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland"},{"name":"Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY"},{"name":"Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, NY"},{"name":"Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Northwell\/Hofstra, Hempstead, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Riecher-R\u00f6ssler","sequence":"additional","affiliation":[{"name":"13Medical Faculty, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Borgwardt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry (UPK), University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Seifritz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0945-5779","authenticated-orcid":false,"given":"Alain","family":"Dagher","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, McGill University, Montreal, QC, 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