{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:58:18Z","timestamp":1790852298619,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["K23MH127300"],"award-info":[{"award-number":["K23MH127300"]}]},{"name":"National Institutes of Health","award":["R01MH108654"],"award-info":[{"award-number":["R01MH108654"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Hypothesis<\/jats:title>\n                  <jats:p>First-line antipsychotics are ineffective in \u223c40% of people with first episode psychosis (FEP). Electroencephalogram (EEG)-based predictive biomarkers could be a scalable solution to reduce trial-and-error.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Study Design<\/jats:title>\n                  <jats:p>We acquired EEG in 56 minimally treated FEP individuals before treatment initiation, and 34 matched healthy controls (HC). Treatment response was defined as &gt;50% improvement in BPRS scores by 12 weeks of treatment. Modified k-means clustering of resting-state EEG yielded six microstates including canonical topographies (A-D). The first principal component (PC1) of microstate properties derived from HCs served as a normative reference onto which FEP patients were projected. Baseline PC1 was used to predict treatment response in adjusted regression analyses. To test stability of results, a second dataset of HCs (n=92) was fitted using the same microstate solution and compared to our native HC dataset. PC1 scores derived from this independent normative dataset were also used for predicting response in FEP.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Study Results<\/jats:title>\n                  <jats:p>\n                    Individual microstates replicated established patient-control differences (e.g., higher presence of microstate C compared to D, p&lt;0.001). PC1 explained 34.8% of variance. Baseline PC1 predicted subsequent treatment response (adjusted OR=0.63, p&lt;0.001), yielding AUC=72.3% in leave-one-out cross-validation (p\n                    <jats:sub>perm<\/jats:sub>\n                    &lt;0.001) when combined with clinical information. PC1 from our HC transported well to the second healthy control EEG dataset (n=92) (r=0.9,p&lt;0.001; r=0.89,p&lt;0.001 ). PC1 in FEP derived using PC1 weights from a second normative dataset also predicted response in FEP (OR=0.70, p=0.03).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>EEG microstate architecture differing from the expected norm is associated with lower odds of treatment response in FEP.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.26.26364042","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:25:11Z","timestamp":1790627111000},"source":"Crossref","is-referenced-by-count":0,"title":["Pre-treatment EEG microstates and response to antipsychotic drugs in first episode psychosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0056-4135","authenticated-orcid":false,"given":"Jose M","family":"Rubio","sequence":"first","affiliation":[{"name":"Donald and Barbara Zucker School of Medicine 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