{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:47:19Z","timestamp":1791830839223,"version":"4.3.4"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T00:00:00Z","timestamp":1597017600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T00:00:00Z","timestamp":1597017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R155-2013-16337"],"award-info":[{"award-number":["R155-2013-16337"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R25-A2701"],"award-info":[{"award-number":["R25-A2701"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R25-A2701"],"award-info":[{"award-number":["R25-A2701"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R155-2013-16337"],"award-info":[{"award-number":["R155-2013-16337"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R155-2013-16337"],"award-info":[{"award-number":["R155-2013-16337"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R25-A2701"],"award-info":[{"award-number":["R25-A2701"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R25-A2701"],"award-info":[{"award-number":["R25-A2701"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R155-2013-16337"],"award-info":[{"award-number":["R155-2013-16337"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R25-A2701"],"award-info":[{"award-number":["R25-A2701"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R155-2013-16337"],"award-info":[{"award-number":["R155-2013-16337"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R246-2016-3237"],"award-info":[{"award-number":["R246-2016-3237"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R25-A2701"],"award-info":[{"award-number":["R25-A2701"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R155-2013-16337"],"award-info":[{"award-number":["R155-2013-16337"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013327","name":"H. Lundbeck A\/S","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013327","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1105825"],"award-info":[{"award-number":["1105825"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The reproducibility of machine-learning analyses in computational psychiatry is a growing concern. In a multimodal neuropsychiatric dataset of antipsychotic-na\u00efve, first-episode schizophrenia patients, we discuss a workflow aimed at reducing bias and overfitting by invoking simulated data in the design process and analysis in two independent machine-learning approaches, one based on a single algorithm and the other incorporating an ensemble of algorithms. We aimed to (1) classify patients from controls to establish the framework, (2) predict short- and long-term treatment response, and (3) validate the methodological framework. We included 138 antipsychotic-na\u00efve, first-episode schizophrenia patients with data on psychopathology, cognition, electrophysiology, and structural magnetic resonance imaging (MRI). Perinatal data and long-term outcome measures were obtained from Danish registers. Short-term treatment response was defined as change in Positive And Negative Syndrome Score (PANSS) after the initial antipsychotic treatment period. Baseline diagnostic classification algorithms also included data from 151 matched controls. Both approaches significantly classified patients from healthy controls with a balanced accuracy of 63.8% and 64.2%, respectively. Post-hoc analyses showed that the classification primarily was driven by the cognitive data. Neither approach predicted short- nor long-term treatment response. Validation of the framework showed that choice of algorithm and parameter settings in the real data was successfully guided by results from the simulated data. In conclusion, this novel approach holds promise as an important step to minimize bias and obtain reliable results with modest sample sizes when independent replication samples are not available.<\/jats:p>","DOI":"10.1038\/s41398-020-00962-8","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T22:02:49Z","timestamp":1597096969000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["A machine-learning framework for robust and reliable prediction of short- and long-term treatment response in initially antipsychotic-na\u00efve schizophrenia patients based on multimodal neuropsychiatric data"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5638-2357","authenticated-orcid":false,"given":"Karen S.","family":"Ambrosen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0664-7924","authenticated-orcid":false,"given":"Martin W.","family":"Skjerb\u00e6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-0382","authenticated-orcid":false,"given":"Jonathan","family":"Foldager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin C.","family":"Axelsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaj","family":"Bak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Arvastson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren R.","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise B.","family":"Johansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayachandra M.","family":"Raghava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob","family":"Oranje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egill","family":"Rostrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette \u00d8.","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-220X","authenticated-orcid":false,"given":"Merete","family":"Osler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitte","family":"Fagerlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9565-0238","authenticated-orcid":false,"given":"Christos","family":"Pantelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J.","family":"Kinon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte Y.","family":"Glenth\u00f8j","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars K.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn H.","family":"Ebdrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,10]]},"reference":[{"key":"962_CR1","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1177\/0269881119855995","volume":"33","author":"K Beck","year":"2019","unstructured":"Beck, K. et al. Prevalence of treatment-resistant psychoses in the community: a naturalistic study. J. Psychopharmacol. 33, 1248\u20131253 (2019).","journal-title":"J. Psychopharmacol."},{"key":"962_CR2","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1176\/appi.ajp.2016.16050503","volume":"174","author":"OD Howes","year":"2016","unstructured":"Howes, O. D. et al. Treatment-resistant schizophrenia: Treatment Response and Resistance in psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. AJP 174, 216\u2013229 (2016).","journal-title":"AJP"},{"key":"962_CR3","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1093\/schbul\/sbs118","volume":"39","author":"SV Haijma","year":"2013","unstructured":"Haijma, S. V. et al. Brain volumes in schizophrenia: a meta-analysis in over 18 000 subjects. Schizophr. Bull. 39, 1129\u20131138 (2013).","journal-title":"Schizophr. Bull."},{"key":"962_CR4","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/mp.2015.63","volume":"21","author":"TGM van Erp","year":"2016","unstructured":"van Erp, T. G. M. et al. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol. Psychiatry 21, 547\u2013553 (2016).","journal-title":"Mol. Psychiatry"},{"key":"962_CR5","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1097\/HRP.0000000000000110","volume":"24","author":"E Owens","year":"2016","unstructured":"Owens, E., Bachman, P., Glahn, D. C. & Bearden, C. E. Electrophysiological endophenotypes for schizophrenia. Harv. Rev. Psychiatry 24, 129\u2013147 (2016).","journal-title":"Harv. Rev. Psychiatry"},{"key":"962_CR6","doi-asserted-by":"publisher","first-page":"101760","DOI":"10.1016\/j.nicl.2019.101760","volume":"22","author":"M Randau","year":"2019","unstructured":"Randau, M. et al. Attenuated mismatch negativity in patients with first-episode antipsychotic-naive schizophrenia using a source-resolved method. NeuroImage: Clin. 22, 101760 (2019).","journal-title":"NeuroImage: Clin."},{"key":"962_CR7","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.schres.2014.06.034","volume":"158","author":"H Fatouros-Bergman","year":"2014","unstructured":"Fatouros-Bergman, H., Cervenka, S., Flyckt, L., Edman, G. & Farde, L. Meta-analysis of cognitive performance in drug-na\u00efve patients with schizophrenia. Schizophr. Res. 158, 156\u2013162 (2014).","journal-title":"Schizophr. Res."},{"key":"962_CR8","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.biopsych.2011.01.032","volume":"70","author":"B Olabi","year":"2011","unstructured":"Olabi, B. et al. Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biol. Psychiatry 70, 88\u201396 (2011).","journal-title":"Biol. Psychiatry"},{"key":"962_CR9","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1093\/schbul\/sbp099","volume":"37","author":"M Leung","year":"2011","unstructured":"Leung, M. et al. Gray matter in first-episode schizophrenia before and after antipsychotic drug treatment. Anatomical likelihood estimation meta-analyses with sample size weighting. Schizophr. Bull. 37, 199\u2013211 (2011).","journal-title":"Schizophr. Bull."},{"key":"962_CR10","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.neuroimage.2016.02.079","volume":"145","author":"MR Arbabshirani","year":"2017","unstructured":"Arbabshirani, M. R., Plis, S., Sui, J. & Calhoun, V. D. Single subject prediction of brain disorders in neuroimaging: promises and pitfalls. NeuroImage 145, 137\u2013165 (2017).","journal-title":"NeuroImage"},{"key":"962_CR11","first-page":"798","volume":"3","author":"RJ Janssen","year":"2018","unstructured":"Janssen, R. J., Mour\u00e3o-Miranda, J. & Schnack, H. G. Making individual prognoses in psychiatry using neuroimaging and machine learning. Biol. Psychiatry.: Cogn. Neurosci. Neuroimaging 3, 798\u2013808 (2018).","journal-title":"Biol. Psychiatry.: Cogn. Neurosci. Neuroimaging"},{"key":"962_CR12","doi-asserted-by":"publisher","unstructured":"Vieira, S. et al. Using machine learning and structural neuroimaging to detect first episode psychosis: reconsidering the evidence. Schizophr. Bull. https:\/\/doi.org\/10.1093\/schbul\/sby189 (2019).","DOI":"10.1093\/schbul\/sby189"},{"key":"962_CR13","doi-asserted-by":"publisher","unstructured":"Winterburn, J. L. et al. Can we accurately classify schizophrenia patients from healthy controls using magnetic resonance imaging and machine learning? A multi-method and multi-dataset study. Schizophr. Res. https:\/\/doi.org\/10.1016\/j.schres.2017.11.038 (2017).","DOI":"10.1016\/j.schres.2017.11.038"},{"key":"962_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41398-018-0355-8","volume":"9","author":"M Cearns","year":"2019","unstructured":"Cearns, M., Hahn, T. & Baune, B. T. Recommendations and future directions for supervised machine learning in psychiatry. Transl. Psychiatry 9, 1\u201312 (2019).","journal-title":"Transl. Psychiatry"},{"key":"962_CR15","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.nicl.2017.06.014","volume":"15","author":"NT Doan","year":"2017","unstructured":"Doan, N. T. et al. Distinct multivariate brain morphological patterns and their added predictive value with cognitive and polygenic risk scores in mental disorders. NeuroImage: Clin. 15, 719\u2013731 (2017).","journal-title":"NeuroImage: Clin."},{"key":"962_CR16","doi-asserted-by":"publisher","unstructured":"Ebdrup, B. H. et al. Accuracy of diagnostic classification algorithms using cognitive-, electrophysiological-, and neuroanatomical data in antipsychotic-na\u00efve schizophrenia patients. Psychol. Med. https:\/\/doi.org\/10.1017\/S0033291718003781 (2018).","DOI":"10.1017\/S0033291718003781"},{"key":"962_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.59","volume":"7","author":"N Bak","year":"2017","unstructured":"Bak, N. et al. Two subgroups of antipsychotic-naive, first-episode schizophrenia patients identified with a Gaussian mixture model on cognition and electrophysiology. Transl. Psychiatry 7, e1087 (2017).","journal-title":"Transl. Psychiatry"},{"key":"962_CR18","unstructured":"Kelleher, J. D., Namee, B. M. & D\u2019Arcy, A. Fundamentals of Machine Learning for Predictive Data Analytics: Algorithms, Worked Examples, and Case Studies (The MIT Press, 2015)."},{"key":"962_CR19","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1080\/15622975.2016.1237042","volume":"18","author":"H N\u00f8rbak-Emig","year":"2017","unstructured":"N\u00f8rbak-Emig, H. et al. Extrastriatal dopamine D 2\/3 receptors and cortical grey matter volumes in antipsychotic-na\u00efve schizophrenia patients before and after initial antipsychotic treatment. World J. Biol. Psychiatry 18, 539\u2013549 (2017).","journal-title":"World J. Biol. Psychiatry"},{"key":"962_CR20","first-page":"444","volume":"4","author":"K Jessen","year":"2019","unstructured":"Jessen, K. et al. Patterns of cortical structures and cognition in antipsychotic-na\u00efve patients with first-episode schizophrenia: a partial least squares correlation analysis. Biol. Psychiatry.: Cogn. Neurosci. Neuroimaging 4, 444\u2013453 (2019).","journal-title":"Biol. Psychiatry.: Cogn. Neurosci. Neuroimaging"},{"key":"962_CR21","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1001\/archpsyc.1990.01810180089012","volume":"47","author":"JK Wing","year":"1990","unstructured":"Wing, J. K. et al. SCAN. Schedules for Clinical Assessment in Neuropsychiatry. Arch. Gen. Psychiatry 47, 589\u2013593 (1990).","journal-title":"Arch. Gen. Psychiatry"},{"key":"962_CR22","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1093\/schbul\/13.2.261","volume":"13","author":"SR Kay","year":"1987","unstructured":"Kay, S. R., Fiszbein, A. & Opler, L. A. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr. Bull. 13, 261\u2013276 (1987).","journal-title":"Schizophr. Bull."},{"key":"962_CR23","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/S2215-0366(15)00575-1","volume":"3","author":"T Wimberley","year":"2016","unstructured":"Wimberley, T. et al. Predictors of treatment resistance in patients with schizophrenia: a population-based cohort study. Lancet Psychiatry 3, 358\u2013366 (2016).","journal-title":"Lancet Psychiatry"},{"key":"962_CR24","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/S0010-9452(78)80049-5","volume":"14","author":"HE Nelson","year":"1978","unstructured":"Nelson, H. E. & O\u2019Connell, A. Dementia: the estimation of premorbid intelligence levels using the New Adult Reading Test. Cortex 14, 234\u2013244 (1978).","journal-title":"Cortex"},{"key":"962_CR25","unstructured":"Wechsler, D. Manual for the Wechsler Adult Intelligence Scale (WAIS) (The Psychological Corporation, 1955)."},{"key":"962_CR26","unstructured":"Wechsler, D. WAIS-III Administration and Scoring Manual (The Psychological Corporation, 1997)."},{"key":"962_CR27","first-page":"266","volume":"5","author":"TW Robbins","year":"1994","unstructured":"Robbins, T. W. et al. Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers. DEM 5, 266\u2013281 (1994).","journal-title":"DEM"},{"key":"962_CR28","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.schres.2003.09.011","volume":"68","author":"RSE Keefe","year":"2004","unstructured":"Keefe, R. S. E. et al. The brief assessment of cognition in schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophr. Res. 68, 283\u2013297 (2004).","journal-title":"Schizophr. Res."},{"key":"962_CR29","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/S0022-5371(73)80034-9","volume":"12","author":"H Buschke","year":"1973","unstructured":"Buschke, H. Selective reminding for analysis of memory and learning. J. Verbal Learn. Verbal Behav. 12, 543\u2013550 (1973).","journal-title":"J. Verbal Learn. Verbal Behav."},{"key":"962_CR30","unstructured":"Smith, A. Symbol Digit Modalities Test (Western Psychological Services, Los Angeles, CA, 1982)."},{"key":"962_CR31","unstructured":"Reitan, R. & Wolfson, D. The Halstead-Reitan Neuropsychological Test Battery: Theory and Clinical Interpretation. Neuropsychology Press; 2nd edition (1993)."},{"key":"962_CR32","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1001\/archneur.1963.00460070100010","volume":"9","author":"B Milner","year":"1963","unstructured":"Milner, B. Effects of different brain lesions on card sorting: the role of the frontal lobes. Arch. Neurol. 9, 90\u2013100 (1963).","journal-title":"Arch. Neurol."},{"key":"962_CR33","unstructured":"Baddeley, A., Emslie, H. & Nimmo-Smith, I. The Speed and Capacity of Language-Processing Test (SCOLP)\u2014Reference Materials (Pearson Assessment, 1992)."},{"key":"962_CR34","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1017\/S0033291718001198","volume":"49","author":"K Jessen","year":"2019","unstructured":"Jessen, K. et al. Cortical structures and their clinical correlates in antipsychotic-na\u00efve schizophrenia patients before and after 6 weeks of dopamine D2\/3 receptor antagonist treatment. Psychol. Med. 49, 754\u2013763 (2019).","journal-title":"Psychol. Med."},{"key":"962_CR35","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1016\/j.neuroimage.2010.07.020","volume":"53","author":"M Reuter","year":"2010","unstructured":"Reuter, M., Rosas, H. D. & Fischl, B. Highly accurate inverse consistent registration: a robust approach. NeuroImage 53, 1181\u20131196 (2010).","journal-title":"NeuroImage"},{"key":"962_CR36","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.neuroimage.2011.02.076","volume":"57","author":"M Reuter","year":"2011","unstructured":"Reuter, M. & Fischl, B. Avoiding asymmetry-induced bias in longitudinal image processing. NeuroImage 57, 19\u201321 (2011).","journal-title":"NeuroImage"},{"key":"962_CR37","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1016\/j.neuroimage.2012.02.084","volume":"61","author":"M Reuter","year":"2012","unstructured":"Reuter, M., Schmansky, N. J., Rosas, H. D. & Fischl, B. Within-subject template estimation for unbiased longitudinal image analysis. NeuroImage 61, 1402\u20131418 (2012).","journal-title":"NeuroImage"},{"key":"962_CR38","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","volume":"31","author":"RS Desikan","year":"2006","unstructured":"Desikan, R. S. et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage 31, 968\u2013980 (2006).","journal-title":"NeuroImage"},{"key":"962_CR39","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.neuroimage.2011.09.015","volume":"62","author":"M Jenkinson","year":"2012","unstructured":"Jenkinson, M., Beckmann, C. F., Behrens, T. E. J., Woolrich, M. W. & Smith, S. M. FSL. NeuroImage 62, 782\u2013790 (2012).","journal-title":"NeuroImage"},{"key":"962_CR40","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1007\/s00213-007-1001-y","volume":"196","author":"KS Jensen","year":"2008","unstructured":"Jensen, K. S., Oranje, B., Wienberg, M. & Glenth\u00f8j, B. Y. The effects of increased serotonergic activity on human sensory gating and its neural generators. Psychopharmacology 196, 631\u2013641 (2008).","journal-title":"Psychopharmacology"},{"key":"962_CR41","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1017\/S1461145707008176","volume":"11","author":"B Oranje","year":"2008","unstructured":"Oranje, B., Jensen, K., Wienberg, M. & Glenth\u00f8j, B. Y. Divergent effects of increased serotonergic activity on psychophysiological parameters of human attention. Int. J. Neuropsychopharmacol. 11, 453\u2013463 (2008).","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"962_CR42","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1093\/schbul\/sbs071","volume":"39","author":"B Oranje","year":"2013","unstructured":"Oranje, B. & Glenth\u00f8j, B. Y. Clonidine normalizes sensorimotor gating deficits in patients with schizophrenia on stable medication. Schizophrenia Bull. 39, 684\u2013691 (2013).","journal-title":"Schizophrenia Bull."},{"key":"962_CR43","doi-asserted-by":"publisher","first-page":"3000","DOI":"10.1038\/npp.2014.152","volume":"39","author":"S D\u00fcring","year":"2014","unstructured":"D\u00fcring, S., Glenth\u00f8j, B. Y., Andersen, G. S. & Oranje, B. Effects of dopamine D2\/D3 blockade on human sensory and sensorimotor gating in initially antipsychotic-naive, first-episode schizophrenia patients. Neuropsychopharmacology 39, 3000\u20133008 (2014).","journal-title":"Neuropsychopharmacology"},{"key":"962_CR44","doi-asserted-by":"publisher","unstructured":"D\u00fcring, S., Glenth\u00f8j, B. Y. & Oranje, B. Effects of blocking D2\/D3 receptors on mismatch negativity and P3a amplitude of initially antipsychotic na\u00efve, first episode schizophrenia patients. Int. J. Neuropsychopharmacol. 19, 3 pyv109, https:\/\/doi.org\/10.1093\/ijnp\/pyv109 (2015).","DOI":"10.1093\/ijnp\/pyv109"},{"key":"962_CR45","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1016\/j.jclinepi.2006.01.014","volume":"59","author":"ART Donders","year":"2006","unstructured":"Donders, A. R. T., van der Heijden, G. J. M. G., Stijnen, T. & Moons, K. G. M. Review: A gentle introduction to imputation of missing values. J. Clin. Epidemiol. 59, 1087\u20131091 (2006).","journal-title":"J. Clin. Epidemiol."},{"key":"962_CR46","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1162\/089976699300016728","volume":"11","author":"ME Tipping","year":"1999","unstructured":"Tipping, M. E. & Bishop, C. M. Mixtures of probabilistic principal component analyzers. Neural Comput. 11, 443\u2013482 (1999).","journal-title":"Neural Comput."},{"key":"962_CR47","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1006\/nimg.1998.0425","volume":"9","author":"LK Hansen","year":"1999","unstructured":"Hansen, L. K. et al. Generalizable patterns in neuroimaging: how many principal components? NeuroImage 9, 534\u2013544 (1999).","journal-title":"NeuroImage"},{"key":"962_CR48","unstructured":"Everitt, B. S. An Introduction to Latent Variable Models (Springer Science & Business Media, 2013)."},{"key":"962_CR49","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/S2215-0366(15)00540-4","volume":"3","author":"E Mouchlianitis","year":"2016","unstructured":"Mouchlianitis, E., McCutcheon, R. & Howes, O. D. Brain-imaging studies of treatment-resistant schizophrenia: a systematic review. Lancet Psychiatry 3, 451\u2013463 (2016).","journal-title":"Lancet Psychiatry"},{"key":"962_CR50","unstructured":"Feurer, M. et al. in Advances in Neural Information Processing Systems Vol. 28 (eds Cortes, C. et al.) 2962\u20132970 (Curran Associates, Inc., 2015)."},{"key":"962_CR51","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.biopsych.2005.01.003","volume":"57","author":"RSE Keefe","year":"2005","unstructured":"Keefe, R. S. E., Eesley, C. E. & Poe, M. P. Defining a cognitive function decrement in schizophrenia. Biol. Psychiatry 57, 688\u2013691 (2005).","journal-title":"Biol. Psychiatry"},{"key":"962_CR52","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1176\/appi.ajp.2008.07081242","volume":"165","author":"KA Woodberry","year":"2008","unstructured":"Woodberry, K. A. & Giuliano, A. J.,. & Seidman, L. J. Premorbid IQ in schizophrenia: a meta-analytic review. Am. J. Psychiatry 165, 579\u2013587 (2008).","journal-title":"Am. J. Psychiatry"},{"key":"962_CR53","first-page":"5248","volume":"97","author":"NB Ipsen","year":"2019","unstructured":"Ipsen, N. B. & Hansen, L. K. Phase transition in PCA with missing data: Reduced signal-to-noise ratio, not sample size! In proceedings of machine learning research. Int. Machine Lean. Society (IMLS) 97, 5248\u20135260 (2019).","journal-title":"Int. Machine Lean. Society (IMLS)"},{"key":"962_CR54","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/eip.12108","volume":"9","author":"M Nordentoft","year":"2015","unstructured":"Nordentoft, M. et al. From research to practice: how OPUS treatment was accepted and implemented throughout Denmark. Early Interv. Psychiatry 9, 156\u2013162 (2015).","journal-title":"Early Interv. Psychiatry"},{"key":"962_CR55","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s11065-009-9114-1","volume":"19","author":"C Pantelis","year":"2009","unstructured":"Pantelis, C. et al. Neurobiological markers of illness onset in psychosis and schizophrenia: the search for a moving target. Neuropsychol. Rev. 19, 385 (2009).","journal-title":"Neuropsychol. Rev."},{"key":"962_CR56","doi-asserted-by":"publisher","unstructured":"Doucet, G. E., Moser, D. A., Luber, M. J., Leibu, E. & Frangou, S. Baseline brain structural and functional predictors of clinical outcome in the early course of schizophrenia. Mol. Psychiatry https:\/\/doi.org\/10.1038\/s41380-018-0269-0 (2018).","DOI":"10.1038\/s41380-018-0269-0"},{"key":"962_CR57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164464","volume":"11","author":"N Bak","year":"2016","unstructured":"Bak, N. & Hansen, L. K. Data driven estimation of imputation error\u2014a strategy for imputation with a reject option. PLoS ONE 11, e0164464 (2016).","journal-title":"PLoS ONE"},{"key":"962_CR58","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0028-3932(71)90067-4","volume":"9","author":"RC Oldfield","year":"1971","unstructured":"Oldfield, R. C. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97\u2013113 (1971).","journal-title":"Neuropsychologia"},{"key":"962_CR59","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.schres.2006.12.015","volume":"91","author":"B Crespo-Facorro","year":"2007","unstructured":"Crespo-Facorro, B. et al. Caudate nucleus volume and its clinical and cognitive correlations in first episode schizophrenia. Schizophr. Res. 91, 87\u201396 (2007).","journal-title":"Schizophr. Res."}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-020-00962-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-020-00962-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-020-00962-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T14:29:52Z","timestamp":1670250592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-020-00962-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,10]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["962"],"URL":"https:\/\/doi.org\/10.1038\/s41398-020-00962-8","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,10]]},"assertion":[{"value":"25 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"N.B., L.A., S.R.C., and B.J.K. are employees at H. Lundbeck A\/S. C.P. has received honoraria for talks at educational meetings and has served on an advisory board for Lundbeck, Australia Pty Ltd. B.H.E. has received lecture fees and\/or is part of Advisory Boards of Bristol-Myers Squibb, Eli Lilly and Company, Janssen-Cilag, Otsuka Pharma Scandinavia AB, Takeda Pharmaceutical Company and Lundbeck Pharma A\/S. B.Y.G. is the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. Her group has also received a research grant from Lundbeck A\/S for another independent investigator-initiated study. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"276"}}