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

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...

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Autores: Segura, Alex G.|||0000-0002-9398-2183, Mezquida, Gisela|||0000-0002-6080-2203, Martínez Piñeiro, Alberto|||0000-0003-2035-5979, Gassó, Patricia|||0000-0001-6930-3454, Rodriguez, Natalia, Moreno-Izco, Lucía, Amoretti, Silvia|||0000-0001-6017-2734, Bioque, Miquel|||0000-0001-6887-7149, Lobo, Antonio|||0000-0002-9098-655X, González-Pinto, Ana|||0000-0002-2568-5179, García-Alcon, Alicia|||0000-0003-1777-1795, Roldan-Bejarano, Alexandra|||0000-0001-9905-3943, Vieta, Eduard|||0000-0002-0548-0053, de la Serna, Elena|||0000-0002-7869-9881, Toll, Alba|||0000-0003-2399-5250, Cuesta, Manuel J.|||0000-0003-0250-5718, Mas, Sergi|||0000-0003-3336-6298, Bernardo, Miquel|||0000-0001-8748-6717
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:291484
Acceso en línea:https://ddd.uab.cat/record/291484
https://dx.doi.org/urn:doi:10.1017/S0033291722001544
Access Level:acceso abierto
Palabra clave:Cognition
Early stages
First-episode psychosis
Genetics
Polygenic risk score
Schizophrenia
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spelling Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episodeSegura, Alex G.|||0000-0002-9398-2183Mezquida, Gisela|||0000-0002-6080-2203Martínez Piñeiro, Alberto|||0000-0003-2035-5979Gassó, Patricia|||0000-0001-6930-3454Rodriguez, NataliaMoreno-Izco, LucíaAmoretti, Silvia|||0000-0001-6017-2734Bioque, Miquel|||0000-0001-6887-7149Lobo, Antonio|||0000-0002-9098-655XGonzález-Pinto, Ana|||0000-0002-2568-5179García-Alcon, Alicia|||0000-0003-1777-1795Roldan-Bejarano, Alexandra|||0000-0001-9905-3943Vieta, Eduard|||0000-0002-0548-0053de la Serna, Elena|||0000-0002-7869-9881Toll, Alba|||0000-0003-2399-5250Cuesta, Manuel J.|||0000-0003-0250-5718Mas, Sergi|||0000-0003-3336-6298Bernardo, Miquel|||0000-0001-8748-6717CognitionEarly stagesFirst-episode psychosisGeneticsPolygenic risk scoreSchizophreniaClinical 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. 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. 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). 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.Universitat Autònoma de Barcelona 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/291484https://dx.doi.org/urn:doi:10.1017/S0033291722001544reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI11/00325Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/01055Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/00612open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2914842026-06-06T12:50:31Z
dc.title.none.fl_str_mv Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode
title Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode
spellingShingle Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode
Segura, Alex G.|||0000-0002-9398-2183
Cognition
Early stages
First-episode psychosis
Genetics
Polygenic risk score
Schizophrenia
title_short Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode
title_full Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode
title_fullStr Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode
title_full_unstemmed Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode
title_sort Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode
dc.creator.none.fl_str_mv Segura, Alex G.|||0000-0002-9398-2183
Mezquida, Gisela|||0000-0002-6080-2203
Martínez Piñeiro, Alberto|||0000-0003-2035-5979
Gassó, Patricia|||0000-0001-6930-3454
Rodriguez, Natalia
Moreno-Izco, Lucía
Amoretti, Silvia|||0000-0001-6017-2734
Bioque, Miquel|||0000-0001-6887-7149
Lobo, Antonio|||0000-0002-9098-655X
González-Pinto, Ana|||0000-0002-2568-5179
García-Alcon, Alicia|||0000-0003-1777-1795
Roldan-Bejarano, Alexandra|||0000-0001-9905-3943
Vieta, Eduard|||0000-0002-0548-0053
de la Serna, Elena|||0000-0002-7869-9881
Toll, Alba|||0000-0003-2399-5250
Cuesta, Manuel J.|||0000-0003-0250-5718
Mas, Sergi|||0000-0003-3336-6298
Bernardo, Miquel|||0000-0001-8748-6717
author Segura, Alex G.|||0000-0002-9398-2183
author_facet Segura, Alex G.|||0000-0002-9398-2183
Mezquida, Gisela|||0000-0002-6080-2203
Martínez Piñeiro, Alberto|||0000-0003-2035-5979
Gassó, Patricia|||0000-0001-6930-3454
Rodriguez, Natalia
Moreno-Izco, Lucía
Amoretti, Silvia|||0000-0001-6017-2734
Bioque, Miquel|||0000-0001-6887-7149
Lobo, Antonio|||0000-0002-9098-655X
González-Pinto, Ana|||0000-0002-2568-5179
García-Alcon, Alicia|||0000-0003-1777-1795
Roldan-Bejarano, Alexandra|||0000-0001-9905-3943
Vieta, Eduard|||0000-0002-0548-0053
de la Serna, Elena|||0000-0002-7869-9881
Toll, Alba|||0000-0003-2399-5250
Cuesta, Manuel J.|||0000-0003-0250-5718
Mas, Sergi|||0000-0003-3336-6298
Bernardo, Miquel|||0000-0001-8748-6717
author_role author
author2 Mezquida, Gisela|||0000-0002-6080-2203
Martínez Piñeiro, Alberto|||0000-0003-2035-5979
Gassó, Patricia|||0000-0001-6930-3454
Rodriguez, Natalia
Moreno-Izco, Lucía
Amoretti, Silvia|||0000-0001-6017-2734
Bioque, Miquel|||0000-0001-6887-7149
Lobo, Antonio|||0000-0002-9098-655X
González-Pinto, Ana|||0000-0002-2568-5179
García-Alcon, Alicia|||0000-0003-1777-1795
Roldan-Bejarano, Alexandra|||0000-0001-9905-3943
Vieta, Eduard|||0000-0002-0548-0053
de la Serna, Elena|||0000-0002-7869-9881
Toll, Alba|||0000-0003-2399-5250
Cuesta, Manuel J.|||0000-0003-0250-5718
Mas, Sergi|||0000-0003-3336-6298
Bernardo, Miquel|||0000-0001-8748-6717
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Cognition
Early stages
First-episode psychosis
Genetics
Polygenic risk score
Schizophrenia
topic Cognition
Early stages
First-episode psychosis
Genetics
Polygenic risk score
Schizophrenia
description 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. 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. 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). 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.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/291484
https://dx.doi.org/urn:doi:10.1017/S0033291722001544
url https://ddd.uab.cat/record/291484
https://dx.doi.org/urn:doi:10.1017/S0033291722001544
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI11/00325
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/01055
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/00612
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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repository.mail.fl_str_mv
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