Juergen Dukart1, Renata Smieskova1, Fabienne Harrisberger1, Claudia Lenz1, André Schmidt1, Anna Walter1, Christian Huber1, Anita Riecher-Rössler1, Andor Simon1, Undine E Lang1, Paolo Fusar-Poli1, Stefan Borgwardt1. 1. From the F. Hoffmann-La Roche, Pharma Research Early Development, Roche Innovation Centre Basel, Basel, Switzerland (Dukart); the Department of Psychiatry (UPK), University of Basel, Basel, Switzerland (Dukart, Smieskova, Lenz, Schmidt, Walter, Huber, Riecher-Rössler, Lang, Borgwardt); the University Hospital of Psychiatry, University Hospital of Bern, Bern, Switzerland, and Specialized Early Psychosis Outpatient Service for Adolescents and Young Adults, Department of Psychiatry, Bruderholz, Switzerland (Simon); and the Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience IoPPN), King's College London, London, UK (Schmidt, Borgwardt).
Abstract
BACKGROUND: There is only limited agreement with respect to location, directionality and functional implications of brain structural alterations observed in patients with schizophrenia. Additionally, their link to occurrence of psychotic symptoms remains unclear. A viable way of addressing these questions is to examine populations in an at-risk mental state (ARMS) before the transition to psychosis. METHODS: We tested for structural brain alterations in individuals in an ARMS compared with healthy controls and patients with first-episode psychosis (FEP) using voxel-based morphometry and measures of cortical thickness. Furthermore, we evaluated if these alterations were modified by age and whether they were linked to the observed clinical symptoms. RESULTS: Our sample included 59 individuals with ARMS, 26 healthy controls and 59 patients with FEP. We found increased grey matter volume and cortical thickness in individuals with ARMS and a similar pattern of structural alterations in patients with FEP. We further found stronger age-related reductions in grey matter volume and cortical thickness in both patients with FEP and individuals with ARMS, linking these alterations to observed clinical symptoms. LIMITATIONS: The ARMS group comprised subgroups with heterogeneous levels of psychosis risk and medication status. Furthermore, the cross-sectional nature of our study and the reduced number of older patients limit conclusions with respect to observed interactions with age. CONCLUSION: Our findings on consistent structural alterations in individuals with ARMS and patients with FEP and their link to clinical symptoms have major implications for understanding their time of occurrence and relevance to psychotic symptoms. Interactions with age found for these alterations may explain the heterogeneity of findings reported in the literature.
BACKGROUND: There is only limited agreement with respect to location, directionality and functional implications of brain structural alterations observed in patients with schizophrenia. Additionally, their link to occurrence of psychotic symptoms remains unclear. A viable way of addressing these questions is to examine populations in an at-risk mental state (ARMS) before the transition to psychosis. METHODS: We tested for structural brain alterations in individuals in an ARMS compared with healthy controls and patients with first-episode psychosis (FEP) using voxel-based morphometry and measures of cortical thickness. Furthermore, we evaluated if these alterations were modified by age and whether they were linked to the observed clinical symptoms. RESULTS: Our sample included 59 individuals with ARMS, 26 healthy controls and 59 patients with FEP. We found increased grey matter volume and cortical thickness in individuals with ARMS and a similar pattern of structural alterations in patients with FEP. We further found stronger age-related reductions in grey matter volume and cortical thickness in both patients with FEP and individuals with ARMS, linking these alterations to observed clinical symptoms. LIMITATIONS: The ARMS group comprised subgroups with heterogeneous levels of psychosis risk and medication status. Furthermore, the cross-sectional nature of our study and the reduced number of older patients limit conclusions with respect to observed interactions with age. CONCLUSION: Our findings on consistent structural alterations in individuals with ARMS and patients with FEP and their link to clinical symptoms have major implications for understanding their time of occurrence and relevance to psychotic symptoms. Interactions with age found for these alterations may explain the heterogeneity of findings reported in the literature.
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