{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:17:19Z","timestamp":1790705839006,"version":"4.1.0"},"reference-count":67,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"Importance<\/jats:title>The link between psychosis and dopaminergic dysfunction is established, but no generalizable biomarkers with clear potential for clinical adoption exist.<\/jats:p><\/jats:sec>Objective<\/jats:title>To replicate previous findings relating neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a proxy measure of dopamine function, to psychosis severity in antipsychotic-free individuals in the psychosis spectrum and to evaluate the out-of-sample predictive ability of NM-MRI for psychosis severity.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This cross-sectional study recruited participants from 2019 to 2023 in the New York City area (main samples) and Mexico City area (external validation sample). The main samples consisted of 42 antipsychotic-free patients with schizophrenia, 53 antipsychotic-free individuals at clinical high risk for psychosis (CHR), and 52 matched healthy controls. An external validation sample consisted of 16 antipsychotic-naive patients with schizophrenia.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>NM-MRI contrast within a subregion of the substantia nigra previously linked to psychosis severity (a priori psychosis region of interest [ROI]) and psychosis severity measured using the Positive and Negative Syndrome Scale (PANSS) in schizophrenia and the Structured Interview for Psychosis-Risk Syndromes (SIPS) in CHR. The cross-validated performance of linear support vector regression to predict psychosis severity across schizophrenia and CHR was assessed, and a final trained model was tested on the external validation sample.<\/jats:p><\/jats:sec>Results<\/jats:title>Of the 163 included participants, 76 (46.6%) were female, and the mean (SD) age was 29.2 (10.4) years. In the schizophrenia sample, higher PANSS positive total scores correlated with higher mean NM-MRI contrast in the psychosis ROI (t<\/jats:italic>37<\/jats:sub>\u2009=\u20092.24,P<\/jats:italic>\u2009=\u2009.03; partialr<\/jats:italic>\u2009=\u20090.35; 95% CI, 0.05 to 0.55). In the CHR sample, no significant association was found between higher SIPS positive total score and NM-MRI contrast in the psychosis ROI (t<\/jats:italic>48<\/jats:sub>\u2009=\u2009\u22120.55,P<\/jats:italic>\u2009=\u2009.68; partialr<\/jats:italic>\u2009=\u2009\u22120.08; 95% CI, \u22120.36 to 0.23). The 10-fold cross-validated prediction accuracy of psychosis severity was above chance in held-out test data (meanr<\/jats:italic>\u2009=\u20090.305,P<\/jats:italic>\u2009=\u2009.01; mean root-mean-square error [RMSE]\u2009=\u20091.001,P<\/jats:italic>\u2009=\u2009.005). External validation prediction accuracy was also above chance (r<\/jats:italic>\u2009=\u20090.422,P<\/jats:italic>\u2009=\u2009.046; RMSE\u2009=\u20090.882,P<\/jats:italic>\u2009=\u2009.047).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>This study provided a direct ROI-based replication of the in-sample association between NM-MRI contrast and psychosis severity in antipsychotic-free patients with schizophrenia. In turn, it failed to replicate such association in CHR individuals. Most critically, cross-validated machine-learning analyses provided a proof-of-concept demonstration that NM-MRI patterns can be used to predict psychosis severity in new data, suggesting potential for developing clinically useful tools.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2023.4305","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T16:03:26Z","timestamp":1699459406000},"page":"198","source":"Crossref","is-referenced-by-count":23,"title":["Generalizability and Out-of-Sample Predictive Ability of Associations Between Neuromelanin-Sensitive Magnetic Resonance Imaging and Psychosis in Antipsychotic-Free Individuals"],"prefix":"10.1001","volume":"81","author":[{"given":"Kenneth","family":"Wengler","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Columbia University, New York, New York"},{"name":"New York State Psychiatric Institute, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth 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