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Ajuts: Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community Seventh Framework Programme. Additional financial support was obtained from the Institut National de la Santé et de la Recherche Médicale (recurrent funding and fellowships) and by Fondation Pierre Deniker. The study received grant 08-MNP-007 from the French government Agence Nationale de la Recherche and grant AOM-07-118 (Influence of Cannabis Psychopathological Outcome in At-risk Mental State [ICAAR study]) from the French Health Ministry Programme Hospitalier de Recherche Clinique. The Sainte-Anne Hospital Center promoted the study. Dr Kempton was supported by a Medical Research Council Fellowship grant MR/J008915/1. Dr Pantelis was supported by Australia's National Health and Medical Research Council Senior Principal Research Fellowship (ID: 628386 & 1105825) and by grant R246-2016-3237 from the Lundbeck Foundation. Dr Barrantes-Vidal was supported by the Ministerio de Ciencia, Innovación e Universidades (PSI2017-87512-C2-1-R), and the Generalitat de Catalunya (2017SGR1612 and ICREA Academia Award). Dr Modinos was supported by a Sir Henry Dale Fellowship #202397/Z/16/Z, jointly funded by The Wellcome Trust and the Royal Society. 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. Is altered emotion recognition associated with adverse clinical and functional outcomes in people at clinical high risk for psychosis? 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. 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. 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. 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. 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. 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. 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