Abstract
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, <65). Within the CHR sample, better anger recognition at baseline was associated with worse functional outcome (odds ratio [OR], 0.88; 95% CI, 0.78-0.99; P =.03). In individuals at CHR with a good functional outcome, positive associations were found between anger recognition and hippocampal volume (ze = 3.91; familywise error [FWE] P =.02) and between fear recognition and medial prefrontal cortex volume (z = 3.60; FWE P =.02), compared with participants with a poor outcome. The onset of psychosis was not associated with baseline emotion recognition performance (neutral OR, 0.93; 95% CI, 0.79-1.09; P =.37; happy OR, 1.03; 95% CI, 0.84-1.25; P =.81; fear OR, 0.98; 95% CI, 0.85-1.13; P =.77; anger OR, 1.00; 95% CI, 0.89-1.12; P =.96). No difference was observed in the association between performance and regional gray matter volumes in individuals at CHR who developed or did not develop psychosis (FWE P <.05). Conclusions and Relevance: In this study, poor functional outcome in individuals at CHR was found to be associated with baseline abnormalities in recognizing negative emotion. This finding has potential implications for the stratification of individuals at CHR and suggests that interventions that target socioemotional processing may improve functional outcomes..
Original language | English |
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Pages (from-to) | 190-200 |
Number of pages | 11 |
Journal | JAMA Psychiatry |
Volume | 77 |
Issue number | 2 |
Early online date | 13 Nov 2019 |
DOIs | |
Publication status | Published - Feb 2020 |
Funding
reported holding 2 patents issued (AU 2015203289; 9884034) and 2 pending (CA2773031; 15/844444). Dr Pantelis reported receiving grants from Australian National Health & Medical Research Council during the conduct of the study; grants from Lundbeck Foundation, personal fees from Lundbeck and Australia Pty Ltd; and personal fees from Lundbeck and Australia Pty Ltd outside the submitted work. Dr Riecher-Rössler reported receiving personal fees from Lundbeck and personal fees from Angelini Pharma outside the submitted work. Dr Bressan reported receiving grants from Fundação de Amparo à Pesquisa do Estado de São Paulo, The Brazilian National Council for Scientific and Technological Development, European Research Council, and Medical Research Council UK during the conduct of the study; personal fees and nonfinancial support from Janssen; personal fees from Pfizer; and personal fees from Sanofi-Aventis outside the submitted work. Dr Krebs reported receiving grants PHRC 07-118 (ICAAR study) from the French Health Ministry during the conduct of the study; participating on the boards of Roche and Janssen; and receiving financial support from Janssen, Otsuka Lundbeck Alliance, and EIsai for conference or dissemination initiatives. Dr Glenthøj reported being the leader of Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research; receiving grants from Medical Research Council and the Lundbeck Foundation during the conduct of the study; and receiving grants from The Lundbeck Foundation and H. Lundbeck A/S outside the submitted work. Dr Ruhrmann reported receiving grants from the European Community during the conduct of the study and personal fees from Boehringer Ingelheim outside the submitted work. Dr Sachs reported receiving grants from European Community Seventh Framework Program during the conduct of the study and personal fees from Lundbeck and Janssen-Cilag outside the submitted work. Dr Rutten reported receiving grants from European Union during the conduct of the study. No other disclosures were reported. National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) 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.
Funders | Funder number |
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EU-GEI | HEALTH-F2-2010-241909 |
European Community | |
French Health Ministry Programme Hospitalier de Recherche Clinique | |
National Health & Medical Research Council | |
National Schizophrenia Networks Studying Gene-Environment Interactions | |
Otsuka Lundbeck Alliance | |
Janssen Biotech | |
Wellcome Trust | |
Medical Research Council | MR/J008915/1, MR/N026063/1, PHRC 07-118 |
Medical Research Council | |
Royal Society | |
European Research Council | |
National Health and Medical Research Council | 628386, 1105825, R246-2016-3237 |
National Health and Medical Research Council | |
Agence Nationale de la Recherche | AOM-07-118 |
Agence Nationale de la Recherche | |
Institut national de la santé et de la recherche médicale | |
Fundação de Amparo à Pesquisa do Estado de São Paulo | |
Generalitat de Catalunya | 2017SGR1612 |
Generalitat de Catalunya | |
Lundbeckfonden | |
Conselho Nacional de Desenvolvimento Científico e Tecnológico | |
Institució Catalana de Recerca i Estudis Avançats | 202397/Z/16/Z |
Institució Catalana de Recerca i Estudis Avançats | |
Ministère des Affaires Sociales et de la Santé | |
Seventh Framework Programme | |
Fondation Pierre Deniker pour la Recherche et la Prévention en Santé Mentale | 08-MNP-007 |
Fondation Pierre Deniker pour la Recherche et la Prévention en Santé Mentale | |
Agencia Santafesina de Ciencia, Tecnología e Innovación | PSI2017-87512-C2-1-R |
Agencia Santafesina de Ciencia, Tecnología e Innovación |