{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:02:08Z","timestamp":1789614128031,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2024GDND02"],"award-info":[{"award-number":["2024GDND02"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Gen. Psychiatry"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Negative symptoms are a core diagnostic domain of schizophrenia that affect functional outcomes and remain difficult to treat. Agomelatine, a novel antidepressant with melatonin receptor agonism and serotonin 2C receptor antagonism, may have therapeutic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aimed to evaluate the efficacy of agomelatine combined with second\u2010generation antipsychotics (SGAs) in reducing negative symptoms and to explore electroencephalogram (EEG)\u2010based biomarkers for predicting treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An open\u2010label randomised parallel\u2010group clinical trial was conducted at the Shanghai Mental Health Centre (December 2022 to September 2023), enrolling outpatient adults with schizophrenia and prominent negative symptoms, defined as a positive and negative syndrome scale factor score for negative symptoms (PANSS\u2010FSNS) higher than a PANSS factor score for positive symptoms (PANSS\u2010FSPS); PANSS\u2010FSNS \u2265 24; 7 &lt; PANSS\u2010FSPS \u2264\u00a028; at least two of three core PANSS negative symptoms \u2265 4 and a Calgary depression scale for schizophrenia score \u2264 18. Patients were randomised (1:1) using a random number table to a group receiving agomelatine (25\u00a0mg\/day) plus SGAs or a group receiving SGAs alone for 12\u00a0weeks. Outcome assessors were blinded after assignment to interventions. The primary outcome was the change in score in the negative symptom factor score (NSFS) at 12\u00a0weeks. Longitudinal changes were assessed using linear mixed\u2010effects models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventy\u2010four patients were enrolled, with an agomelatine augmentation group (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a037) and a control group (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a037). The agomelatine augmentation group demonstrated significantly lower scores on the NSFS compared to the control group starting from Week 8 (estimated marginal mean [EMM] difference\u00a0=\u00a0\u22121.79, 95% confidence interval [CI] \u22123.00 to \u22120.59,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.004) and sustaining through Week 12 (EMM difference\u00a0=\u00a0\u22122.65, 95% CI \u22123.86 to \u22121.44,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Exploratory support vector machine (SVM) models demonstrated high classification performance in distinguishing treatment responders from non\u2010responders (area under the curve\u00a0=\u00a00.91), highlighting notable EEG changes in the left frontotemporal region.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Agomelatine augmentation significantly improves negative symptoms, encompassing affective deficits, expressive impairments and social\u2010withdrawal\u2010related symptoms. EEG\u2010based SVM models suggest potential utility for informing future personalised treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NCT05646264.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/gps3.70045","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:13:52Z","timestamp":1789611232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Agomelatine as augmentation therapy with second\u2010generation antipsychotics for negative symptoms of schizophrenia: An open\u2010label randomised clinical trial and electroencephalogram\u2010derived model for treatment response prediction"],"prefix":"10.1002","volume":"39","author":[{"given":"Wanyan","family":"Zhou","sequence":"first","affiliation":[{"name":"Shanghai Jiao Tong 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