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
Pages (from-to)249–258
Number of pages10
JournalSchizophrenia Bulletin
Issue number1
Early online date7 Jul 2020
Publication statusPublished - 23 Jan 2021


  • depression
  • gray matter volume
  • machine learning
  • psychopathology
  • psychosis
  • schizophrenia
  • Humans
  • Male
  • Depression/classification
  • Gray Matter/diagnostic imaging
  • Young Adult
  • Magnetic Resonance Imaging
  • Adolescent
  • Adult
  • Female
  • Schizophrenia/classification
  • Psychotic Disorders/classification
  • Supervised Machine Learning
  • Principal Component Analysis


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