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Antipsychotic dopamine D2 receptor (D2R) antagonism has been associated with striatal volume increases, but effects of partial D2R agonism by newer antipsychotics are largely unexplored. This study aimed to compare short\u2010term brain changes associated with either D2R antagonism or partial D2R agonism using normative modeling. Secondarily, the study aimed to explore long\u2010term effects following naturalistic treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Antipsychotic\u2010na\u00efve patients with first\u2010episode psychosis received 6\u2009weeks of monotherapy with either amisulpride (D2R antagonist) (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200941) or aripiprazole (partial D2R agonist) (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200945). All patients underwent structural magnetic resonance imaging before and after 6\u2009weeks of treatment. A subset was re\u2010scanned at 6\u2009months, 1\u2009year, and 2\u2009years of naturalistic treatment. A pretrained normative model was applied to 186 subcortical and cortical regions. We used Wilcoxon signed\u2010rank tests to identify longitudinal structural deviations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Amisulpride and aripiprazole were associated with striatal volume increases after 6\u2009weeks. No cortical effects were observed with amisulpride. Thinning of the temporal lobe was observed with aripiprazole. After 6\u2009months, and 1 and 2\u2009years, the striatal changes abated but cortical thinning in the frontal lobes emerged.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Both partial D2R agonism and D2R antagonism appear linked to striatal volume increases; however, changes appear transient. Conversely, frontal thinning occurs over time and appears less closely linked to antipsychotic treatment. Interpreting structural brain changes in patients with psychosis require consideration of short\u2010term pharmacological effects as well as factors related to illness progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pcn.70017","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T07:22:17Z","timestamp":1767684137000},"page":"224-232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring brain structural effects of dopaminergic antagonism and partial agonism in antipsychotic\u2010na\u00efve patients with first\u2010episode psychosis using normative modeling"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9701-6022","authenticated-orcid":false,"given":"Anna","family":"Feveile","sequence":"first","affiliation":[{"name":"Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center, Glostrup Copenhagen 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Mental Health Services CPH  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora R.","family":"Bu\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition, and Behaviour Radboud University Medical Centre  Nijmegen Netherlands"},{"name":"Department of Medical Neuroscience Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre F.","family":"Marquand","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition, and Behaviour Radboud University Medical Centre  Nijmegen Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birte Y.","family":"Glenth\u00f8j","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center, Glostrup Copenhagen University Hospital \u2010 Mental Health Services CPH  Copenhagen 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