The Psychopathology and Neuroanatomical Markers of Depression in Early Psychosis

Rachel Upthegrove*, Paris Lalousis, Pavan Mallikarjun, Katharine Chisholm, Sian Lowri Griffiths, Mariam Iqbal, Mirabel Pelton, Renate Reniers, Alexandra Stainton, Marlene Rosen, Anne Ruef, Dominic B Dwyer, Marian Surman, Theresa Haidl, Nora Penzel, Lana Kambeitz-llankovic, Alessandro Bertolino, Paolo Brambilla, Stefan Borgwardt, Joseph KambeitzRebekka Lencer, Christos Pantelis, Stephan Ruhrmann, Frauke Schultze-lutter, Raimo K R Salokangas, Eva Meisenzahl, Stephen J Wood, Nikolaos Koutsouleris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Depression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depression would be identifiable by symptoms and neuroanatomical features similar to those seen in recent-onset depression (ROD). Data were extracted from the multisite PRONIA study: 154 ROP patients (FEP within 3 months of treatment onset), of whom 83 were depressed (ROP+D) and 71 who were not depressed (ROP−D), 146 ROD patients, and 265 healthy controls (HC). Analyses included a (1) principal component analysis that established the similar symptom structure of depression in ROD and ROP+D, (2) supervised machine learning (ML) classification with repeated nested cross-validation based on depressive symptoms separating ROD vs ROP+D, which achieved a balanced accuracy (BAC) of 51%, and (3) neuroanatomical ML-based classification, using regions of interest generated from ROD subjects, which identified BAC of 50% (no better than chance) for separation of ROP+D vs ROP−D. We conclude that depression at a symptom level is broadly similar with or without psychosis status in recent-onset disorders; however, this is not driven by a separable depressed subgroup in FEP. Depression may be intrinsic to early stages of psychotic disorder, and thus treating depression could produce widespread benefit.
Original languageEnglish
JournalSchizophrenia Bulletin
Early online date7 Jul 2020
Publication statusE-pub ahead of print - 7 Jul 2020


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