{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:18:32Z","timestamp":1789471112189,"version":"build-2803163510"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission Seventh Framework Program","award":["HEALTH-F2-2010-242114"],"award-info":[{"award-number":["HEALTH-F2-2010-242114"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background and Hypothesis: Treatment response in first-episode psychosis varies substantially, yet underlying factors remain poorly understood. Symptom network theory suggests that inter-symptom relationships may influence treatment response. We hypothesized that symptom networks at baseline, as well as dynamic interactions over time, would differ between remitters and non-remitters, and that specific antipsychotics would show differential symptom-targeting effects.<\/jats:p>\n                  <jats:p>Study Design: We compared baseline and temporal symptom networks between remitters (n\u2009=\u2009250) and non-remitters (n\u2009=\u2009196) from the OPTiMiSE trial using 21-item Positive and Negative Syndrome Scale (PANSS) data. Baseline networks were estimated using Gaussian graphical models and compared with the Network Comparison Test. Temporal networks across baseline, week 2, and week 4 were modeled using Cross-Lagged Panel Network analysis. Key symptoms were identified by in- and out-prediction values. Group differences were assessed via non-zero edge weight correlations and Jaccard Index (JI). Network Intervention Analysis was used to examine differential effects of continuing amisulpride versus switching to olanzapine in non-responders (n\u2009=\u200985).<\/jats:p>\n                  <jats:p>Study Results: Baseline networks did not differ between outcome groups. However, temporal networks showed substantial differences: remitters and non-remitters had minimal overlap in symptom connections (baseline\u2192week 2: JI\u2009=\u20090.014; week 2\u00a0\u2192\u00a0week 4: JI\u2009=\u20090.055) and virtually no correlation in connection strengths (baseline\u2192week 2: r\u2009=\u2009-0.089, P = .447; week 2\u00a0\u2192\u00a0week 4: r\u2009=\u20090.005, P = .968). Key nodes (highest in\/out-prediction) differed between groups. No robust symptom-specific medication effects emerged.<\/jats:p>\n                  <jats:p>Conclusions: Temporal symptom dynamics, rather than static baseline relationships, differentiate response trajectories and could inform future research on early markers of non-remission. Absence of antipsychotic-specific effects suggests generic treatment mechanisms.<\/jats:p>","DOI":"10.1093\/schbul\/sbag016","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T10:20:15Z","timestamp":1774088415000},"source":"Crossref","is-referenced-by-count":2,"title":["Symptom Network Dynamics during Antipsychotic Treatment in First-Episode Psychosis"],"prefix":"10.1093","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0913-805X","authenticated-orcid":false,"given":"Melissa G","family":"Zandstra","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University Medical Center Utrecht , Utrecht , 3584 CX,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floortje E","family":"Scheepers","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University Medical Center Utrecht , Utrecht , 3584 CX,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6226-2258","authenticated-orcid":false,"given":"Gabriela","family":"Lunansky","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam University Medical Centers, VUMC, Amsterdam, 1081 BT, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Galderisi","sequence":"additional","affiliation":[{"name":"University of Campania Department of Mental and Physical Health and Preventive Medicine, , Luigi Vanvitelli, Naples , 81100,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte Y","family":"Glenth\u00f8j","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen University Hospital, Mental Health Center Glostrup , Glostrup , 2600,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , 2200,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Winter-van Rossum","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University Medical Center Utrecht , Utrecht , 3584 CX,","place":["The Netherlands"]},{"name":"Department of Psychiatry, Icahn School of Medicine , Mount Sinai, New York , 10029,","place":["United States"]},{"name":"Department of Psychiatry, University of Oxford , Warneford Hospital, Oxford , OX3 7JX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metten","family":"Somers","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University Medical Center Utrecht , Utrecht , 3584 CX,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"van Dellen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University Medical Center Utrecht , Utrecht , 3584 CX,","place":["The Netherlands"]},{"name":"Department of Neurology, UZ Brussel and Vrije Universiteit Brussel , Brussels , 1090,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"key":"2026032106200506100_ref1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fpsyt.2016.00116","article-title":"Suicide in the early stage of schizophrenia","volume":"7","author":"Ventriglio","year":"2016","journal-title":"Front Psychiatry"},{"key":"2026032106200506100_ref2","doi-asserted-by":"publisher","first-page":"e566","DOI":"10.4088\/JCP.13m08606","article-title":"The relative contribution of cognition and symptomatic remission to functional outcome following treatment of a first episode of psychosis","volume":"75","author":"Jordan","year":"2014","journal-title":"J Clin Psychiatry"},{"key":"2026032106200506100_ref3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/wps.20375","article-title":"A network theory of mental disorders","volume":"16","author":"Borsboom","year":"2017","journal-title":"World Psychiatry"},{"key":"2026032106200506100_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-818697-8.00044-3","article-title":"Ongoing and future challenges of the network approach to psychopathology: from theoretical conjectures to clinical translations","volume":"11","author":"Blanchard","year":"2022","journal-title":"Compr Clin Psychol"},{"key":"2026032106200506100_ref5","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1001\/jamapsychiatry.2015.2079","article-title":"Association of symptom network structure with the course of depression","volume":"72","author":"van Borkulo","year":"2015","journal-title":"JAMA Psychiatry"},{"key":"2026032106200506100_ref6","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.jad.2021.11.059","article-title":"The network analysis of depressive symptoms before and after two weeks of antidepressant treatment","volume":"299","author":"Zhou","year":"2022","journal-title":"J Affect Disord"},{"key":"2026032106200506100_ref7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.eclinm.2019.02.009","article-title":"Structure and connectivity of depressive symptom networks corresponding to early treatment response","volume":"8","author":"McElroy","year":"2019","journal-title":"EClinicalMedicine."},{"key":"2026032106200506100_ref8","first-page":"59","article-title":"Sensitivity of the positive and negative syndrome scale (PANSS) in detecting treatment effects via network analysis","volume":"14","author":"Esfahlani","year":"2017","journal-title":"Innov Clin Neurosci"},{"key":"2026032106200506100_ref9","doi-asserted-by":"publisher","first-page":"3193","DOI":"10.1017\/S0033291720005280","article-title":"Longitudinal symptom network structure in first-episode psychosis: a possible marker for remission","volume":"52","author":"Piao","year":"2022","journal-title":"Psychol Med"},{"key":"2026032106200506100_ref10","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1093\/schbul\/sbac131","article-title":"Longitudinal network analysis reveals interactive change of schizophrenia symptoms during acute antipsychotic treatment","volume":"49","author":"Sun","year":"2023","journal-title":"Schizophr Bull"},{"key":"2026032106200506100_ref11","doi-asserted-by":"crossref","first-page":"104202","DOI":"10.1016\/j.ajp.2024.104202","article-title":"Dynamics of symptom network in patients with first-episode schizophrenia: insight from the CNFEST project","volume":"101","author":"Zhang","year":"2024","journal-title":"Asian J Psychiatry"},{"key":"2026032106200506100_ref12","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1159\/000495045","article-title":"Introducing network intervention analysis to investigate sequential, symptom-specific treatment effects: a demonstration in co-occurring insomnia and depression","volume":"88","author":"Blanken","year":"2019","journal-title":"Psychother Psychosom"},{"key":"2026032106200506100_ref13","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1093\/schbul\/sbv019","article-title":"The optimization of treatment and management of schizophrenia in Europe (OPTiMiSE) trial: rationale for its methodology and a review of the effectiveness of switching antipsychotics","volume":"41","author":"Leucht","year":"2015","journal-title":"Schizophr Bull"},{"key":"2026032106200506100_ref14","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/S2215-0366(18)30252-9","article-title":"Amisulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three-phase switching study","volume":"5","author":"Kahn","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"2026032106200506100_ref15","first-page":"22","article-title":"The MINI-international neuropsychiatric interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10","volume":"59","author":"Sheehan","year":"1998","journal-title":"J Clin Psychiatry"},{"key":"2026032106200506100_ref16","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/schbul\/13.2.261","article-title":"The positive and negative syndrome scale (PANSS) for schizophrenia","volume":"13","author":"Kay","year":"1987","journal-title":"Schizophr Bull"},{"key":"2026032106200506100_ref17","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1176\/appi.ajp.162.3.441","article-title":"Remission in schizophrenia: proposed criteria and rationale for consensus","volume":"162","author":"Andreasen","year":"2005","journal-title":"Am J Psychiatry"},{"key":"2026032106200506100_ref18","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/s41537-024-00499-5","article-title":"The dimensional structure of the positive and negative syndrome scale in first-episode schizophrenia spectrum disorders: an exploratory graph analysis from the OPTiMiSE trial","volume":"10","author":"Dal Santo","year":"2024","journal-title":"Schizophrenia."},{"key":"2026032106200506100_ref19","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3390\/psych3030032","article-title":"Estimating the stability of psychological dimensions via bootstrap exploratory graph analysis: a Monte Carlo simulation and tutorial","volume":"3","author":"Christensen","year":"2021","journal-title":"Psych."},{"key":"2026032106200506100_ref20","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/biostatistics\/kxm045","article-title":"Sparse inverse covariance estimation with the graphical lasso","volume":"9","author":"Friedman","year":"2008","journal-title":"Biostatistics."},{"key":"2026032106200506100_ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v048.i04","article-title":"Qgraph: network visualizations of relationships in psychometric data","volume":"48","author":"Epskamp","year":"2012","journal-title":"J Stat Softw"},{"key":"2026032106200506100_ref22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v042.i08","article-title":"MatchIt: nonparametric preprocessing for parametric causal inference","volume":"42","author":"Ho","year":"2011","journal-title":"J Stat Softw"},{"key":"2026032106200506100_ref23","doi-asserted-by":"publisher","first-page":"e33","DOI":"10.1192\/j.eurpsy.2022.25","article-title":"Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: a network analysis from the OPTiMiSE trial","volume":"65","author":"Dal Santo","year":"2022","journal-title":"Eur Psychiatry"},{"key":"2026032106200506100_ref24","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1037\/abn0000181","article-title":"Identifying highly influential nodes in the complicated grief network","volume":"125","author":"Robinaugh","year":"2016","journal-title":"J Abnorm Psychol"},{"key":"2026032106200506100_ref25","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3758\/s13428-017-0862-1","article-title":"Estimating psychological networks and their accuracy: a tutorial paper","volume":"50","author":"Epskamp","year":"2018","journal-title":"Behav Res Methods"},{"key":"2026032106200506100_ref26","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1037\/met0000476","article-title":"Comparing network structures on three aspects: a permutation test","volume":"28","author":"van Borkulo","year":"2023","journal-title":"Psychol Methods"},{"key":"2026032106200506100_ref27","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2023"},{"key":"2026032106200506100_ref28","article-title":"NetworkComparisonTest: statistical comparison of two networks based on three invariance measures (2.2.1) [computer software]","author":"Van Borkulo"},{"key":"2026032106200506100_ref29","volume-title":"Adv Psychology","author":""},{"key":"2026032106200506100_ref30","doi-asserted-by":"publisher","first-page":"e0148171","DOI":"10.1371\/journal.pone.0148171","article-title":"Use of Wishart prior and simple extensions for sparse precision matrix estimation","volume":"11","author":"Kuismin","year":"2016","journal-title":"PLoS One"},{"key":"2026032106200506100_ref31","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1037\/met0000537","article-title":"We need to change how we compute RMSEA for nested model comparisons in structural equation modeling","volume":"29","author":"Savalei","year":"2023","journal-title":"Psychol Methods"},{"key":"2026032106200506100_ref32","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.jpsychires.2021.07.053","article-title":"Distinct trajectories of depression symptoms in early and middle adolescence: preliminary evidence from longitudinal network analysis","volume":"142","author":"Rubin","year":"2021","journal-title":"J Psychiatr Res"},{"key":"2026032106200506100_ref33","doi-asserted-by":"crossref","first-page":"6205475","DOI":"10.1155\/da\/6205475","article-title":"Longitudinal associations between anxiety and depressive symptoms in adolescence, early adulthood, and old age: cross-lagged panel network analyses","volume":"2024","author":"Wang","year":"2024","journal-title":"Depress Anxiety"},{"key":"2026032106200506100_ref34","doi-asserted-by":"publisher","first-page":"e18134","DOI":"10.7717\/peerj.18134","article-title":"Longitudinal relations between non-suicidal self-injury and both depression and anxiety among senior high school adolescents: a cross-lagged panel network analysis","volume":"12","author":"Zhao","year":"2024","journal-title":"PeerJ."},{"key":"2026032106200506100_ref35","doi-asserted-by":"publisher","first-page":"e13040","DOI":"10.1111\/jora.13040","article-title":"Unraveling depressive symptom networks: a three-year longitudinal study among Chinese junior high school adolescents","volume":"35","author":"Zhao","year":"2025","journal-title":"J Res Adolesc"},{"key":"2026032106200506100_ref36","first-page":"547","article-title":"\u00c9tude comparative de la distribution florale dans Une portion des Alpes et des Jura","volume":"37","author":"Jaccard","year":"1901","journal-title":"Bull Soc Vaudoise Sci Nat"},{"key":"2026032106200506100_ref37","article-title":"Further generalizations of the Jaccard Index","author":"Costa"},{"key":"2026032106200506100_ref38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized linear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J Stat Softw"},{"key":"2026032106200506100_ref39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v048.i02","article-title":"Lavaan: an R package for structural equation modeling","volume":"48","author":"Rosseel","year":"2012","journal-title":"J Stat Softw"},{"key":"2026032106200506100_ref40","doi-asserted-by":"publisher","volume-title":"J Stat Software","author":"","DOI":"10.18637\/jss.v093.i08"},{"key":"2026032106200506100_ref41","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3758\/s13428-017-0910-x","article-title":"How well do network models predict observations? On the importance of predictability in network models","volume":"50","author":"Haslbeck","year":"2018","journal-title":"Behav Res Methods"},{"key":"2026032106200506100_ref42","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1139\/jpn.0611","article-title":"The \"delayed onset\" of antipsychotic action\u2014an idea whose time has come and gone: 2004 innovations in neuropsychopharmacology award paper","volume":"31","author":"Agid","year":"2006","journal-title":"J Psychiatry Neurosci"},{"key":"2026032106200506100_ref43","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.schres.2011.11.008","article-title":"Symptom severity and attitudes toward medication: impacts on adherence in outpatients with schizophrenia","volume":"134","author":"Yang","year":"2012","journal-title":"Schizophr Res"},{"key":"2026032106200506100_ref44","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1159\/000366489","article-title":"Which aspects of long-term outcome are predicted by positive and negative symptoms in early-onset psychosis? An exploratory eight-year follow-up study","volume":"48","author":"Remberk","year":"2015","journal-title":"Psychopathology."},{"key":"2026032106200506100_ref45","doi-asserted-by":"crossref","first-page":"113039","DOI":"10.1016\/j.psychres.2020.113039","article-title":"Temporal dynamics of suspiciousness and hallucinations in clinical high risk and first episode psychosis","volume":"290","author":"Hermans","year":"2020","journal-title":"Psychiatry Res"},{"key":"2026032106200506100_ref46","doi-asserted-by":"publisher","first-page":"A455","DOI":"10.1016\/j.jval.2014.08.1244","article-title":"Social contacts reduce negative symptoms, especially emotional withdrawal in patients with schizophrenia","volume":"17","author":"Millier","year":"2014","journal-title":"Value Health"},{"key":"2026032106200506100_ref47","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1176\/appi.ajp.2020.20020147","article-title":"On the origins of schizophrenia","volume":"177","author":"Kahn","year":"2020","journal-title":"Am J Psychiatry"},{"key":"2026032106200506100_ref48","doi-asserted-by":"crossref","first-page":"15067","DOI":"10.1038\/nrdp.2015.67","volume":"1","author":"Kahn","year":"2015","journal-title":"Schizophrenia Nat Rev Dis Primers"},{"key":"2026032106200506100_ref49","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41537-024-00489-7","article-title":"Long-term clinical recovery and treatment resistance in first-episode psychosis: a 10-year follow-up study","volume":"10","author":"Wold","year":"2024","journal-title":"Schizophrenia."},{"key":"2026032106200506100_ref50","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1037\/met0000466","article-title":"Investigating the feasibility of idiographic network models","volume":"28","author":"Mansueto","year":"2023","journal-title":"Psychol Methods"},{"key":"2026032106200506100_ref51","doi-asserted-by":"crossref","first-page":"104163","DOI":"10.1016\/j.brat.2022.104163","article-title":"Quantifying and addressing the impact of measurement error in network models","volume":"157","author":"de Ron","year":"2022","journal-title":"Behav Res Ther"}],"container-title":["Schizophrenia Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/schizophreniabulletin\/article-pdf\/52\/2\/sbag016\/67454649\/sbag016.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/schizophreniabulletin\/article-pdf\/52\/2\/sbag016\/67454649\/sbag016.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T10:20:19Z","timestamp":1774088419000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/schizophreniabulletin\/article\/doi\/10.1093\/schbul\/sbag016\/8532621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,3,21]]},"published-print":{"date-parts":[[2026,3,7]]}},"URL":"https:\/\/doi.org\/10.1093\/schbul\/sbag016","relation":{},"ISSN":["0586-7614","1745-1701"],"issn-type":[{"value":"0586-7614","type":"print"},{"value":"1745-1701","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,3]]},"article-number":"sbag016"}}