Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode
Por:
Segura, AG, Mezquida, G, Martinez-Pinteno, A, Gasso, P, Rodriguez, N, Moreno-Izco, L, Amoretti, S, Bioque, M, Lobo, A, Gonzalez-Pinto, A, Garcia-Alcon, A, Roldan-Bejarano, A, Vieta, E, de la Serna, E, Toll, A, Cuesta, MJ, Mas, S, Bernardo, M
Publicada:
1 ene 2023
Ahead of Print:
1 jun 2022
Resumen:
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.
Filiaciones:
Segura, AG:
Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain
Mezquida, G:
Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain
Neurosci Inst Hosp Clin Barcelona, Barcelona Clin Schizophrenia Unit, Barcelona, Spain
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAP, Barcelona, Spain
Martinez-Pinteno, A:
Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain
Gasso, P:
Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAP, Barcelona, Spain
Rodriguez, N:
Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain
Moreno-Izco, L:
Complejo Hosp Navarra, Dept Psychiat, Pamplona, Spain
Navarra Inst Hlth Res IdiSNA, Pamplona, Spain
Amoretti, S:
Neurosci Inst Hosp Clin Barcelona, Barcelona Clin Schizophrenia Unit, Barcelona, Spain
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Vall dHebron Res Inst VHIR, Psychiat Genet Unit, Grp Psychiat Mental Hlth & Addict, Barcelona, Spain
Univ Barcelona, Hosp Clin, Inst Neurosci, Bipolar & Depress Disorders Unit, Barcelona, Spain
Bioque, M:
Neurosci Inst Hosp Clin Barcelona, Barcelona Clin Schizophrenia Unit, Barcelona, Spain
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAP, Barcelona, Spain
Univ Barcelona, Dept Med, Barcelona, Spain
Lobo, A:
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Univ Zaragoza, Dept Med & Psychiat, Zaragoza, Spain
Inst Invest Sanitaria Aragon IIS Aragon, Zaragoza, Spain
Gonzalez-Pinto, A:
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Hosp Univ Alava, Vitoria, Spain
Inst Invest Sanitaria Bioaraba, Vitoria, Spain
Univ Basque Country, Vizcaya, Spain
Garcia-Alcon, A:
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Hosp Gen Univ Gregorio Maranon, Inst Psychiat & Mental Hlth, Inst Invest Sanitaria Gregorio Maranon IiSGM, Dept Child & Adolescent Psychiat, Madrid, Spain
Roldan-Bejarano, A:
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Univ Autonoma Barcelona UAB, Inst Invest Biomed SantPau IIB SANTPAU, Psychiat Dept, Hosp Santa Creu & St Pau, Barcelona, Spain
Vieta, E:
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Univ Barcelona, Hosp Clin, Inst Neurosci, Bipolar & Depress Disorders Unit, Barcelona, Spain
Univ Barcelona, Dept Med, Barcelona, Spain
de la Serna, E:
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAP, Barcelona, Spain
Univ Barcelona, Dept Med, Barcelona, Spain
Univ Barcelona, Clin Inst Neurosci, Dept Child & Adolescent Psychiat & Psychol, Barcelona, Spain
Toll, A:
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Parc Salut Mar, Inst Neuropsychiat & Addict, Barcelona, Spain
Hosp Mar Med Res Inst, Barcelona, Spain
Cuesta, MJ:
Complejo Hosp Navarra, Dept Psychiat, Pamplona, Spain
Navarra Inst Hlth Res IdiSNA, Pamplona, Spain
Mas, S:
Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAP, Barcelona, Spain
Bernardo, M:
Neurosci Inst Hosp Clin Barcelona, Barcelona Clin Schizophrenia Unit, Barcelona, Spain
Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAP, Barcelona, Spain
Univ Barcelona, Dept Med, Barcelona, Spain
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