Association of Adverse Outcomes With Emotion Processing and Its Neural Substrate in Individuals at Clinical High Risk for Psychosis

Gemma Modinos*, Matthew J. Kempton, Stefania Tognin, Maria Calem, Lilla Porffy, Mathilde Antoniades, Ava Mason, Matilda Azis, Paul Allen, Barnaby Nelson, Patrick McGorry, Christos Pantelis, Anita Riecher-Rossler, Stefan Borgwardt, Rodrigo Bressan, Neus Barrantes-Vidal, Marie-Odile Krebs, Merete Nordentoft, Birte Glenthoj, Stephan RuhrmannGabriele Sachs, Bart Rutten, Jim van Os, Lieuwe de Haan, Eva Velthorst, Mark van der Gaag, Lucia R. Valmaggia, Philip McGuire, Philip McGuire, Matthew J. Kempton, Gemma Modinos, Lieuwe de Haan, Tamar C. Kraan, Daniella S. van Dam, Nadine Burger, G. Paul Amminger, Athena Politis, Joanne Goodall, Charlotte Rapp, Philippe A. Delespaul, EU-GEI High Risk Study Group

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


This case-control study analyzes emotion recognition and neuroimaging data as well as clinical and functional outcomes for individuals at risk for transition to psychosis and those without psychiatric or neurological disorders.

Question Is altered emotion recognition associated with adverse clinical and functional outcomes in people at clinical high risk for psychosis? Findings In this case-control study of 213 individuals at clinical high risk for psychosis and 52 healthy participants, abnormalities in the recognition of negative emotion at baseline were associated with neuroanatomical alterations in the medial prefrontal cortex and hippocampus and with a low level of functioning at a 12-month follow-up. Meaning This study found that, in people with high risk for developing psychosis, functional outcomes are associated with the degree to which their emotion processing is altered.

Importance The development of adverse clinical outcomes in patients with psychosis has been associated with behavioral and neuroanatomical deficits related to emotion processing. However, the association between alterations in brain regions subserving emotion processing and clinical outcomes remains unclear. Objective To examine the association between alterations in emotion processing and regional gray matter volumes in individuals at clinical high risk (CHR) for psychosis, and the association with subsequent clinical outcomes. Design, Setting, and Participants This naturalistic case-control study with clinical follow-up at 12 months was conducted from July 1, 2010, to August 31, 2016, and collected data from 9 psychosis early detection centers (Amsterdam, Basel, Cologne, Copenhagen, London, Melbourne, Paris, The Hague, and Vienna). Participants (213 individuals at CHR and 52 healthy controls) were enrolled in the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) project. Data were analyzed from October 1, 2018, to April 24, 2019. Main Measures and Outcomes Emotion recognition was assessed with the Degraded Facial Affect Recognition Task. Three-Tesla magnetic resonance imaging scans were acquired from all participants, and gray matter volume was measured in regions of interest (medial prefrontal cortex, amygdala, hippocampus, and insula). Clinical outcomes at 12 months were evaluated for transition to psychosis using the Comprehensive Assessment of At-Risk Mental States criteria, and the level of overall functioning was measured through the Global Assessment of Functioning [GAF] scale. Results A total of 213 individuals at CHR (105 women [49.3%]; mean [SD] age, 22.9 [4.7] years) and 52 healthy controls (25 women [48.1%]; mean [SD] age, 23.3 [4.0] years) were included in the study at baseline. At the follow-up within 2 years of baseline, 44 individuals at CHR (20.7%) had developed psychosis and 169 (79.3%) had not. Of the individuals at CHR reinterviewed with the GAF, 39 (30.0%) showed good overall functioning (GAF score, >= 65), whereas 91 (70.0%) had poor overall functioning (GAF score,

Original languageEnglish
Pages (from-to)190-200
Number of pages11
JournalJAMA Psychiatry
Issue number2
Publication statusPublished - Feb 2020




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