Polygenic risk score of glycemic homeostasis, Type 2 Diabetes Mellitus and glycemic components in first episode psychosis
Por:
Segura AG, Verdolini N, Valli I, Garcia-Rizo C, Diaz-Caneja CM, Vieta E, Mezquida G, Lobo A, Gonzalez-Pinto A, Andreu-Bernabeu Á, Roldan A, Martinez-Aran A, Baeza I, Mane A, Labad J, Müller DJ, Guasch-Capella N, Bernardo M, Mas S, Bioque M, Gonzalez J, Andrés P, Cavone V, Corripio I, Duque A, Mar-Barrutia L, Marin J, De-la-Camara C, Vaquero-Puyuelo D, Rivero O, Fabra MJE, Trabsa A, Legido T, Forte MF, Serra-Navarro M, de la Serna H, Castro-Fornielles J, Contreras F, García-Portilla MP, González-Blanco L, Echevarría RS, Rabadán AZ, Rodriguez-Jimenez R, Martínez-Gras I, Usall J, Barajas A, Sarro S, Pomarol-Clotet E, Ibañez A and Cuesta MJ
Publicada:
1 nov 2025
Ahead of Print:
1 oct 2025
Resumen:
Objective: First episode of psychosis (FEP) is associated with glucose homeostasis abnormalities even before pharmacological intervention. Given inconclusive GWAS results regarding a direct genetic link between schizophrenia and type 2 diabetes mellitus (T2DM), we hypothesized that FEP patients may exhibit altered genetic risk for glycemic traits. We compared polygenic risk scores (PRS) for T2DM (PRST2DM), fasting glucose (PRSFG), and glycated hemoglobin (HbA1c) (PRSHbA1c) between FEP patients and controls, examining their associations with glycemic measures over 24 months. Methods: We analyzed data from 242 FEP patients and 119 controls, assessing fasting serum glucose and HbA1c at baseline and 24 months. We examined cross-sectional and longitudinal associations between PRS and glycemic measures within each group. Results: FEP patients and controls did not differ significantly in PRS. Significant associations were observed for PRSFG with baseline serum glucose in controls (p = 0.008), PRSFG during follow-up (p = 0.034), PRSHbA1c at 24 months (p = 0.018), and HbA1c longitudinally (p = 0.025). After multiple testing corrections, only the association between PRSFG and baseline serum glucose in controls remained significant (p_adj = 0.023). No associations were found for PRST2DM. Conclusions: Despite the link between FEP and glycemic disturbances, PRST2DM did not differ between FEP patients and controls. However, PRS for glycemic traits showed associations with glycemic measures in both groups before multiple testing correction, suggesting that genetic predisposition may influence glucose homeostasis in early psychosis. The absence of a direct association between common genetic variants underlying T2DM and early glycemic dysregulation in FEP underscores the importance of considering environmental factors and epigenetic mechanisms.
Filiaciones:
Segura AG:
Bipolar and Depressive Disorders Unit, Neuroscience Institute, Hospital Clinic de Barcelona, Barcelona, Spain
Verdolini N:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Mental Health, Umbria, 1 Mental Health Center, Perugia, Italy
Valli I:
Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
Garcia-Rizo C:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Barcelona Clínic Schizophrenia Unit (BCSU), Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain
University of Barcelona, Medicine Department, Barcelona, Spain
Diaz-Caneja CM:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
Vieta E:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
University of Barcelona, Medicine Department, Barcelona, Spain
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
Mezquida G:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Barcelona Clínic Schizophrenia Unit (BCSU), Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
Lobo A:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Medicine and Psychiatry, Universidad de Zaragoza, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
Gonzalez-Pinto A:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Psychiatry, Hospital Universitario de Alava, UPV/EHU, BIOARABA, Vitoria, Spain
Andreu-Bernabeu Á:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
Roldan A:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Psychiatry, Institut d'Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Martinez-Aran A:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
University of Barcelona, Medicine Department, Barcelona, Spain
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
Baeza I:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
University of Barcelona, Medicine Department, Barcelona, Spain
Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clínic de Barcelona, Barcelona, Spain
Mane A:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Hospital del Mar Medical Research Institute (IMIM), Pompeu Fabra University, Barcelona, Spain
Labad J:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Hospital de Mataró, Consorci Sanitari del Maresme, Fundació Parc Taulí, Mataró, Catalonia, Spain
Institut d'Innovació i Investigació Parc Taulí (I3PT), Translational Neuroscience Research Unit I3PT-Inc-UAB, Institut de Neurociències, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
Müller DJ:
Department of Psychiatry, University of Toronto, Toronto, Canada
Centre for Addiction and Mental Health, Toronto, Canada
Guasch-Capella N:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Barcelona Clínic Schizophrenia Unit (BCSU), Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain
University of Barcelona, Medicine Department, Barcelona, Spain
Bernardo M:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Barcelona Clínic Schizophrenia Unit (BCSU), Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain
University of Barcelona, Medicine Department, Barcelona, Spain
Mas S:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
Bioque M:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Barcelona Clínic Schizophrenia Unit (BCSU), Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain
University of Barcelona, Medicine Department, Barcelona, Spain
Gonzalez J:
UR Center for Mental Health-CERSAME, School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
Clinica Nuestra Señora de la Paz, Bogota, Colombia
Andrés P:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
Cavone V:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
Corripio I:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Psychiatry, Institut d'Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Duque A:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Psychiatry, Institut d'Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Mar-Barrutia L:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Psychiatry, Hospital Universitario de Alava, UPV/EHU, BIOARABA, Vitoria, Spain
Marin J:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Psychiatry, Hospital Universitario de Alava, UPV/EHU, BIOARABA, Vitoria, Spain
De-la-Camara C:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Medicine and Psychiatry, Universidad de Zaragoza, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
Vaquero-Puyuelo D:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Medicine and Psychiatry, Universidad de Zaragoza, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
Rivero O:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Genetics, University of Valencia, Campus of Burjassot, Valencia, Spain
Biomedical Research Institute INCLIVA, Fundación Investigación Hospital Clínico de Valencia, Valencia, Spain
Fabra MJE:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Biomedical Research Institute INCLIVA, Fundación Investigación Hospital Clínico de Valencia, Valencia, Spain
Department of Psychiatry, Hospital Clínico Universitario de Valencia, Spain
Trabsa A:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Hospital del Mar Medical Research Institute (IMIM), Pompeu Fabra University, Barcelona, Spain
Legido T:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Hospital del Mar Medical Research Institute (IMIM), Pompeu Fabra University, Barcelona, Spain
Forte MF:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
Serra-Navarro M:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain
de la Serna H:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clínic de Barcelona, Barcelona, Spain
Castro-Fornielles J:
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
University of Barcelona, Medicine Department, Barcelona, Spain
Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clínic de Barcelona, Barcelona, Spain
Contreras F:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Bellvitge Biomedical Research Institute IDIBELL, Department of Psychiatry- Bellvitge University, Spain
García-Portilla MP:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Psychiatry, Universidad de Oviedo, Servicio de Salud del Principado de Asturias (SESPA) Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, Spain
González-Blanco L:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Psychiatry, Universidad de Oviedo, Servicio de Salud del Principado de Asturias (SESPA) Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, Spain
Echevarría RS:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Cruces University Hospital, BioCruces Health Research Institute, University of the Basque Country (UPV/EHU) Vizcaya, Spain
Rabadán AZ:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
BioCruces Health Research Institute, University of the Basque Country (UPV/EHU), Department of Neurosciences, Vizcaya, Spain
Rodriguez-Jimenez R:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Universidad Complutense de Madrid (UCM), Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain
Martínez-Gras I:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, RETIC (Network of Addictive Conditions), Institute of Health Carlos III, Madrid, Spain
Usall J:
Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Parc Sanitari Sant Joan de Déu, Spain
Barajas A:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain
Hospital Materno Infantil Sant Joan de Déu, Esplugues de Llobregat, Spain
Sarro S:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
FIDMAG Germanes Hospitalàries Research Foundation, Sant Boi de Llobregat, Barcelona, Spain
Pomarol-Clotet E:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
FIDMAG Germanes Hospitalàries Research Foundation, Sant Boi de Llobregat, Barcelona, Spain
Ibañez A:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
Department of Psychiatry, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain
Cuesta MJ:
Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Instituto de Investigación Sanitaria de Navarra (IdiSNa), Pamplona, Spain
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