Investigating the causal pathways among psychopathological variables, cognitive impairment, and real-life functioning in people with schizophrenia

Abstract The present study aimed to investigate the causal relationships among cognitive impairment, psychopathology, and real-life functioning in a large sample of people with schizophrenia, using a data-driven causal discovery procedure based on partial ancestral graphs (PAGs). This method may pro...

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Main Authors: Luigi Giuliani, Francesco Sanmarchi, Armida Mucci, Paola Rucci, Edoardo Caporusso, Paola Bucci, Giulia M. Giordano, Mario Amore, Paola Rocca, Alessandro Rossi, Alessandro Bertolino, Silvana Galderisi, Mario Maj
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Schizophrenia
Online Access:https://doi.org/10.1038/s41537-024-00545-2
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author Luigi Giuliani
Francesco Sanmarchi
Armida Mucci
Paola Rucci
Edoardo Caporusso
Paola Bucci
Giulia M. Giordano
Mario Amore
Paola Rocca
Alessandro Rossi
Alessandro Bertolino
Silvana Galderisi
Mario Maj
author_facet Luigi Giuliani
Francesco Sanmarchi
Armida Mucci
Paola Rucci
Edoardo Caporusso
Paola Bucci
Giulia M. Giordano
Mario Amore
Paola Rocca
Alessandro Rossi
Alessandro Bertolino
Silvana Galderisi
Mario Maj
author_sort Luigi Giuliani
collection DOAJ
description Abstract The present study aimed to investigate the causal relationships among cognitive impairment, psychopathology, and real-life functioning in a large sample of people with schizophrenia, using a data-driven causal discovery procedure based on partial ancestral graphs (PAGs). This method may provide additional insights for the identification of potential therapeutic targets to promote recovery in people with chronic schizophrenia. State-of-the-art instruments were used to assess the study variables. Two PAGs were generated at baseline and after 4 years of follow-up to model the nature of the causal relationships linking psychopathology, cognition, and functioning. The study sample was composed of more than 600 clinically stable patients with schizophrenia at two time points. The PAGs model indicated that working memory impairment is the first ancestor of the causal links, influencing all the other neurocognitive domains, social cognition, and functional capacity, which in turn affects everyday life functioning. From this domain of functioning a causal link is directed to disorganization and positive symptoms, and another to work skills and interpersonal relationships domains; the latter had a direct link to asociality and the other domains of negative symptoms. The structure of the PAGs did not differ significantly between baseline and follow-up, indicating the stability of the causal relationship model investigated cross-sectionally at both time points. The role of working memory impairment in the pathways to functional outcomes in schizophrenia highlights the importance of implementing integrated pharmacological and cognitive remediation interventions targeting neurocognition. The impact of everyday life and interpersonal functioning on the clinical presentation of schizophrenia suggests that integrated and personalized treatments, promoting relevant skills to improve these functional outcomes, may have a beneficial impact on clinical outcomes.
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spelling doaj-art-f5ffb8d3ebea4a0e8e8e28ab45eca8ba2025-01-05T12:33:26ZengNature PortfolioSchizophrenia2754-69932025-01-0111111210.1038/s41537-024-00545-2Investigating the causal pathways among psychopathological variables, cognitive impairment, and real-life functioning in people with schizophreniaLuigi Giuliani0Francesco Sanmarchi1Armida Mucci2Paola Rucci3Edoardo Caporusso4Paola Bucci5Giulia M. Giordano6Mario Amore7Paola Rocca8Alessandro Rossi9Alessandro Bertolino10Silvana Galderisi11Mario Maj12Department of Psychiatry, University of Campania “Luigi Vanvitelli”Department of Biomedical and Neuromotor Sciences, University of BolognaDepartment of Psychiatry, University of Campania “Luigi Vanvitelli”Department of Biomedical and Neuromotor Sciences, University of BolognaDepartment of Psychiatry, University of Campania “Luigi Vanvitelli”Department of Psychiatry, University of Campania “Luigi Vanvitelli”Department of Psychiatry, University of Campania “Luigi Vanvitelli”Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of GenoaDepartment of Neuroscience, Section of Psychiatry, University of TurinDepartment of Biotechnological and Applied Clinical Sciences, Section of Psychiatry, University of L’AquilaDepartment of Basic Medical Science, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’Department of Psychiatry, University of Campania “Luigi Vanvitelli”Department of Psychiatry, University of Campania “Luigi Vanvitelli”Abstract The present study aimed to investigate the causal relationships among cognitive impairment, psychopathology, and real-life functioning in a large sample of people with schizophrenia, using a data-driven causal discovery procedure based on partial ancestral graphs (PAGs). This method may provide additional insights for the identification of potential therapeutic targets to promote recovery in people with chronic schizophrenia. State-of-the-art instruments were used to assess the study variables. Two PAGs were generated at baseline and after 4 years of follow-up to model the nature of the causal relationships linking psychopathology, cognition, and functioning. The study sample was composed of more than 600 clinically stable patients with schizophrenia at two time points. The PAGs model indicated that working memory impairment is the first ancestor of the causal links, influencing all the other neurocognitive domains, social cognition, and functional capacity, which in turn affects everyday life functioning. From this domain of functioning a causal link is directed to disorganization and positive symptoms, and another to work skills and interpersonal relationships domains; the latter had a direct link to asociality and the other domains of negative symptoms. The structure of the PAGs did not differ significantly between baseline and follow-up, indicating the stability of the causal relationship model investigated cross-sectionally at both time points. The role of working memory impairment in the pathways to functional outcomes in schizophrenia highlights the importance of implementing integrated pharmacological and cognitive remediation interventions targeting neurocognition. The impact of everyday life and interpersonal functioning on the clinical presentation of schizophrenia suggests that integrated and personalized treatments, promoting relevant skills to improve these functional outcomes, may have a beneficial impact on clinical outcomes.https://doi.org/10.1038/s41537-024-00545-2
spellingShingle Luigi Giuliani
Francesco Sanmarchi
Armida Mucci
Paola Rucci
Edoardo Caporusso
Paola Bucci
Giulia M. Giordano
Mario Amore
Paola Rocca
Alessandro Rossi
Alessandro Bertolino
Silvana Galderisi
Mario Maj
Investigating the causal pathways among psychopathological variables, cognitive impairment, and real-life functioning in people with schizophrenia
Schizophrenia
title Investigating the causal pathways among psychopathological variables, cognitive impairment, and real-life functioning in people with schizophrenia
title_full Investigating the causal pathways among psychopathological variables, cognitive impairment, and real-life functioning in people with schizophrenia
title_fullStr Investigating the causal pathways among psychopathological variables, cognitive impairment, and real-life functioning in people with schizophrenia
title_full_unstemmed Investigating the causal pathways among psychopathological variables, cognitive impairment, and real-life functioning in people with schizophrenia
title_short Investigating the causal pathways among psychopathological variables, cognitive impairment, and real-life functioning in people with schizophrenia
title_sort investigating the causal pathways among psychopathological variables cognitive impairment and real life functioning in people with schizophrenia
url https://doi.org/10.1038/s41537-024-00545-2
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