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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Characterizing the Social Epigenome in Mexican Patients with Early−Onset Psychosis

by
David Ruiz-Ramos
1,†,
José Jaime Martínez-Magaña
2,3,4,†,
Isela Esther Juárez-Rojop
1,
Germán Alberto Nolasco-Rosales
1,
Fernanda Sosa-Hernández
5,
Juan Daniel Cruz-Castillo
1,
Josefa Cavazos
5,
Adriana Callejas
5,
Patricia Zavaleta-Ramírez
5,
José Antonio Zorrilla-Dosal
5,
Nuria Lanzagorta
6,
Humberto Nicolini
6,7,
Janitza L. Montalvo-Ortiz
2,3,4,
David C. Glahn
8,9,10 and
Alma Delia Genis-Mendoza
5,7,*
1
Academic Division of Health Sciences, Juárez Autonomous University of Tabasco (UJAT), Villahermosa 86100, Mexico
2
Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT 06520, USA
3
VA Connecticut Healthcare System, West Haven, CT 06516, USA
4
U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, West Haven, CT 06516, USA
5
Dr. Juan N. Navarro Children’s Psychiatric Hospital, National Commission on Mental Health and Addictions (CONASAMA), Ministry of Health, Mexico City 14080, Mexico
6
Carracci Medical Group, Department of Clinical Research, Mexico City 03740, Mexico
7
Genomics Laboratory of Psychiatric, Neurodegenerative, and Addiction Disorders, National Institute of Genomic Medicine (INMEGEN), Ministry of Health Mexico City 14610, Mexico
8
Department of Psychiatry and Behavioral Sciences, Boston Children’s Hospital, Boston, MA 02115, USA
9
Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA
10
Olin Neuropsychiatry Research Center, Institute of Living, Hartford, CT 06106, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Genes 2025, 16(5), 591; https://doi.org/10.3390/genes16050591 (registering DOI)
Submission received: 19 March 2025 / Revised: 25 April 2025 / Accepted: 9 May 2025 / Published: 17 May 2025
(This article belongs to the Section Neurogenomics)
Versions Notes

Abstract

Background: Psychosis is one of the leading causes of disability worldwide. Individuals with early−onset psychosis (EOP) tend to experience a worse prognosis and shorter life expectancy. The etiology of EOP remains unclear, but epigenetic mechanisms are known to serve as the interface between environmental exposures and biological processes to better understand its etiology. Objectives: We characterized the sociodemographic and clinical characteristics, as well as genome-wide epigenetic markers, in Mexican patients with EOP. Methods: We estimated epigenetic age, performed an epigenome−wide association study, and finally developed an epigenetic risk score (MRS) to predict manifestations of psychosis. Results: We found that patients with EOP have a higher epigenetic age using Wu’s clock (p = 0.015). Moreover, accelerated epigenetic age was correlated with chronological age (PedBE clock, p = 0.046), global functioning (Wu’s clock, p = 0.027), and psychiatric admissions (DNAmTL, p = 0.038). In addition, we observed that a reduction in years of schooling is associated with an increase on epigenetic age (Levine’s clock, β = 5.07, p = 0.001). In our epigenome-wide association study, we identified eight CpGs associated with EOP. Noteworthy, a psychosis−methylation risk score (EOP−MRS) was associated with panic disorder (β = 1.36, p = 0.03), as well as auditory (β = 1.28, p = 0.04) and visual (β = 1.22, p = 0.04) hallucinations. Conclusions: Years of education have an impact on epigenetic age. Additionally, our study suggests associations of DNA methylation with EOP. Finally, we developed an MRS that associates clinical manifestations of psychosis.
Keywords: early−onset psychosis; epigenome−wide association study; methylation risk score; Mexico; adolescents early−onset psychosis; epigenome−wide association study; methylation risk score; Mexico; adolescents

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MDPI and ACS Style

Ruiz-Ramos, D.; Martínez-Magaña, J.J.; Juárez-Rojop, I.E.; Nolasco-Rosales, G.A.; Sosa-Hernández, F.; Cruz-Castillo, J.D.; Cavazos, J.; Callejas, A.; Zavaleta-Ramírez, P.; Zorrilla-Dosal, J.A.; et al. Characterizing the Social Epigenome in Mexican Patients with Early−Onset Psychosis. Genes 2025, 16, 591. https://doi.org/10.3390/genes16050591

AMA Style

Ruiz-Ramos D, Martínez-Magaña JJ, Juárez-Rojop IE, Nolasco-Rosales GA, Sosa-Hernández F, Cruz-Castillo JD, Cavazos J, Callejas A, Zavaleta-Ramírez P, Zorrilla-Dosal JA, et al. Characterizing the Social Epigenome in Mexican Patients with Early−Onset Psychosis. Genes. 2025; 16(5):591. https://doi.org/10.3390/genes16050591

Chicago/Turabian Style

Ruiz-Ramos, David, José Jaime Martínez-Magaña, Isela Esther Juárez-Rojop, Germán Alberto Nolasco-Rosales, Fernanda Sosa-Hernández, Juan Daniel Cruz-Castillo, Josefa Cavazos, Adriana Callejas, Patricia Zavaleta-Ramírez, José Antonio Zorrilla-Dosal, and et al. 2025. "Characterizing the Social Epigenome in Mexican Patients with Early−Onset Psychosis" Genes 16, no. 5: 591. https://doi.org/10.3390/genes16050591

APA Style

Ruiz-Ramos, D., Martínez-Magaña, J. J., Juárez-Rojop, I. E., Nolasco-Rosales, G. A., Sosa-Hernández, F., Cruz-Castillo, J. D., Cavazos, J., Callejas, A., Zavaleta-Ramírez, P., Zorrilla-Dosal, J. A., Lanzagorta, N., Nicolini, H., Montalvo-Ortiz, J. L., Glahn, D. C., & Genis-Mendoza, A. D. (2025). Characterizing the Social Epigenome in Mexican Patients with Early−Onset Psychosis. Genes, 16(5), 591. https://doi.org/10.3390/genes16050591

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