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Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode

Published online by Cambridge University Press:  09 June 2022

Alex G. Segura
Affiliation:
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
Gisela Mezquida
Affiliation:
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain Barcelona Clínic Schizophrenia Unit, Neuroscience Institute Hospital Clínic de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain
Albert Martínez-Pinteño
Affiliation:
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
Patricia Gassó
Affiliation:
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain
Natalia Rodriguez
Affiliation:
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
Lucía Moreno-Izco
Affiliation:
Department of Psychiatry, Complejo Hospitalario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
Silvia Amoretti
Affiliation:
Barcelona Clínic Schizophrenia Unit, Neuroscience Institute Hospital Clínic de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Group of Psychiatry, Mental Health and Addictions, Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, Barcelona, Spain
Miquel Bioque
Affiliation:
Barcelona Clínic Schizophrenia Unit, Neuroscience Institute Hospital Clínic de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain Department of Medicine, University of Barcelona, Barcelona, Spain
Antonio Lobo
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
Ana González-Pinto
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Hospital Universitario de Alava, Vitoria-Gasteiz, Spain Instituto de Investigación Sanitaria Bioaraba, Vitoria-Gasteiz, Spain University of the Basque Country, Vizcaya, Spain
Alicia García-Alcon
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
Alexandra Roldán-Bejarano
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Psychiatry Department, Institut d'Investigació Biomèdica-SantPau (IIB-SANTPAU), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Eduard Vieta
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, Barcelona, Spain Department of Medicine, University of Barcelona, Barcelona, Spain
Elena de la Serna
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain Department of Medicine, University of Barcelona, Barcelona, Spain Department of Child and Adolescent Psychiatry and Psychology, Clínic Institute of Neurosciences, University of Barcelona, Barcelona, Spain
Alba Toll
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Institute of Neuropsychiatry and Addiction, Parc de Salut Mar, Barcelona, Spain Hospital del Mar Medical Research Institute, Barcelona, Spain
Manuel J. Cuesta
Affiliation:
Department of Psychiatry, Complejo Hospitalario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
Sergi Mas*
Affiliation:
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain
Miquel Bernardo
Affiliation:
Barcelona Clínic Schizophrenia Unit, Neuroscience Institute Hospital Clínic de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain Department of Medicine, University of Barcelona, Barcelona, Spain
PEPs Group
Affiliation:
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
*
Author for correspondence: Sergi Mas, E-mail: sergimash@ub.edu

Abstract

Background

Clinical intervention in early stages of psychotic disorders is crucial for the prevention of severe symptomatology trajectories and poor outcomes. Genetic variability is studied as a promising modulator of prognosis, thus novel approaches considering the polygenic nature of these complex phenotypes are required to unravel the mechanisms underlying the early progression of the disorder.

Methods

The sample comprised of 233 first-episode psychosis (FEP) subjects with clinical and cognitive data assessed periodically for a 2-year period and 150 matched controls. Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, education attainment and cognitive performance were used to assess the genetic risk of FEP and to characterize their association with premorbid, baseline and progression of clinical and cognitive status.

Results

Schizophrenia, bipolar disorder and cognitive performance PRSs were associated with an increased risk of FEP [false discovery rate (FDR) ⩽ 0.027]. In FEP patients, increased cognitive PRSs were found for FEP patients with more cognitive reserve (FDR ⩽ 0.037). PRSs reflecting a genetic liability for improved cognition were associated with a better course of symptoms, functionality and working memory (FDR ⩽ 0.039). Moreover, the PRS of depression was associated with a worse trajectory of the executive function and the general cognitive status (FDR ⩽ 0.001).

Conclusions

Our study provides novel evidence of the polygenic bases of psychosis and its clinical manifestation in its first stage. The consistent effect of cognitive PRSs on the early clinical progression suggests that the mechanisms underlying the psychotic episode and its severity could be partially independent.

Type
Original Article
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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Footnotes

*

Both authors contributed equally to the manuscript.

PEPs Group: García-Rizo, Clemente (Barcelona Clínic Schizophrenia Unit, Neuroscience Institute Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain); Forte, M Florencia (Barcelona Clínic Schizophrenia Unit, Neuroscience Institute Hospital Clínic de Barcelona, Barcelona, Spain); Pina-Camacho, Laura and Parellada, Mara (Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), School of Medicine, Universidad Complutense, Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain); Grasa, Eva and Alonso-Solís, Anna (Psychiatry Department, Institut d'Investigació Biomèdica-SantPau (IIB-SANTPAU), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain); Zorrilla, Iñaki and García Corres, Edurne (Hospital Universitario de Alava, Vitoria-Gasteiz, Spain; Instituto de Investigación Sanitaria Bioaraba, Vitoria-Gasteiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; University of the Basque Country, Vizcaya, Spain); Modrego-Pardo, Pedro (Hospital Universitario Miguel Servet and Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain; Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain); Rovero, Olga (Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Biomedical Research Institute INCLIVA, Fundación Investigación Hospital Clínico de Valencia, Valencia, Spain; Departament of Genetics, Universitat de València, Valencia, Spain); Escarti, Maria José (Department of Psychiatry, Hospital Clínico Universitario de Valencia; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Biomedical Research Institute INCLIVA, Fundación Investigación Hospital Clínico de Valencia, Valencia, Spain); Martínez-Sadurní, Laura and Trabsa, Amira (Institute of Neuropsychiatry and Addiction, Parc de Salut Mar, Barcelona, Spain); Jimenez, Esther and Verdolini, Norma (Hospital Clínic de Barcelona, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain); Castro-Fornieles, Josefina (Department of Child and Adolescent Psychiatry and Psychology, Clínic Institute of Neurosciences, Hospital Clínic de Barcelona, University of Barcelona; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain); Baeza, Imma (Department of Child and Adolescent Psychiatry and Psychology, Clínic Institute of Neurosciences, Hospital Clínic de Barcelona, University of Barcelona; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain); Contreras Fernandez, Fernando (Psychiatric Service, Bellvitge Universitary Hospital, IDIBELL, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain); Bobes, Julio and García-Portilla, María Paz (Área de Psiquiatría, Universidad de Oviedo, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain); Segarra Echevarría, Rafael (Cruces University Hospital, BioCruces Health Research Institute, University of the Basque Country (UPV/EHU), Vizcaya, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain); Zabala Rabadán, Arantzazu (University of the Basque Country (UPV/EHU) Vizcaya, Spain; BioCruces Health Research Institute, Vizcaya, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain); Sanchez-Pastor, Luis (Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain); Rodriguez-Jimenez, Roberto (Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; CogPsy Group, Universidad Complutense de Madrid (UCM), Madrid, Spain); Butjosa, Anna (Parc Sanitari Sant Joan de Déu, Teaching, Research & Innovation Unit, Sant Boi de Llobregat, Spain; Hospital Infanto-juvenil Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain); Usall, Judith (Parc Sanitari Sant Joan de Déu, Teaching, Research & Innovation Unit, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain); Pomarol-Clotet, Edith and Sarró, Salvador (FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain); Ibáñez, Ángela (Department of Psychiatry, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain); Sánchez-Torres, Ana M. (Department of Psychiatry, Complejo Hospitalario de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain); Balanzá-Martínez, Vicent (Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Valencia, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid).

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