{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:15:02Z","timestamp":1793661302691,"version":"4.5.1"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:sec id=\"ab-ybr250007-4\"><jats:title>Importance<\/jats:title><jats:p>There is limited neurobiological or trial evidence guiding treatment of comorbid affective syndromes in psychotic disorders. Given the use of dopamine-blocking antipsychotics, understanding dopamine function across these mood states is warranted.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250007-5\"><jats:title>Objective<\/jats:title><jats:p>To test for differences in dopamine synthesis capacity (Ki<jats:sup>cer<\/jats:sup>) between affective syndromes across psychotic disorders and for association with psychotic symptom severity.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250007-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>In this cross-sectional study using fluorine F 18\u2013labeled fluorodopa (<jats:sup>18<\/jats:sup>F-DOPA) positron emission tomography (PET), individuals with first-episode psychosis and comorbid affective syndromes, including a current major depressive episode (MDE) or mixed\/mania syndromes, and matched controls were recruited from early intervention services in inner-city London, United Kingdom. Data were collected from March 2013 to February 2022 and analyzed from October 1, 2023, to January 1, 2025.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250007-7\"><jats:title>Exposure<\/jats:title><jats:p>Striatal Ki<jats:sup>cer<\/jats:sup> measured by <jats:sup>18<\/jats:sup>F-DOPA PET.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250007-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Striatal Ki<jats:sup>cer<\/jats:sup> and scores on the Positive and Negative Syndrome Scale, Hamilton Depression Rating Scale, Montgomery-\u00c5sberg Depression Rating Scale, and Young Mania Rating Scale were determined.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250007-9\"><jats:title>Results<\/jats:title><jats:p>The study included a total of 76 individuals (38 with first-episode psychosis and comorbid affective syndromes [25 with MDE and 13 with mixed\/mania syndromes] and 38 matched controls). The mean (SD) age was 27.2 (8.9) years overall, 30.7 (12.8) years among those with MDE, 23.7 (3.1) years among those with mixed\/mania syndromes, and 26.0 (6.0) years among controls. Sex distribution did not differ (MDE, 13 [52%] male; mixed\/mania syndromes, 8 [62%] male; controls, 25 [66%] male; <jats:italic>P<\/jats:italic>\u2009=\u2009.56). Ki<jats:sup>cer<\/jats:sup> (controlling for age and sex) was significant across groups in whole striatum (<jats:italic>F<\/jats:italic><jats:sub>2,71<\/jats:sub>\u2009=\u20094.04; <jats:italic>P<\/jats:italic>\u2009=\u2009.02; <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.13). People with psychosis and MDE had lower Ki<jats:sup>cer<\/jats:sup> compared with those with psychosis and mixed\/mania syndromes (\u03b2 [SE], 0.014 [0.001]; <jats:italic>P<\/jats:italic>\u2009=\u2009.02), with the largest difference observed in the limbic striatum (Cohen <jats:italic>d<\/jats:italic>\u2009=\u20091.57; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001). In the overall psychosis sample, higher striatal Ki<jats:sup>cer<\/jats:sup> was associated with greater positive psychotic symptoms (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.13; \u03b2 [SE], 0.000066 [0.000030]; <jats:italic>P<\/jats:italic>\u2009=\u2009.03), notably in the associative striatum (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.15; <jats:italic>P<\/jats:italic>\u2009=\u2009.02). No significant association was found in the limbic striatum.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250007-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Ki<jats:sup>cer<\/jats:sup> was lower in psychosis and comorbid MDE than mixed\/mania syndromes, and transdiagnostically, greater positive psychotic symptoms were associated with higher Ki<jats:sup>cer<\/jats:sup> in the associative, but not limbic, striatum. This subregion dopamine dysregulation has relevance for dopamine-modulating therapeutic agents and drug discovery.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2025.1811","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T15:00:34Z","timestamp":1755097234000},"page":"1009","source":"Crossref","is-referenced-by-count":11,"title":["Dopamine and Mood in Psychotic Disorders"],"prefix":"10.1001","volume":"82","author":[{"given":"Sameer","family":"Jauhar","sequence":"first","affiliation":[{"name":"Division of Psychiatry, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"McCutcheon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Oxford, United Kingdom"},{"name":"Oxford Health NHS Foundation Trust, Oxford, United Kingdom"},{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, 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