{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:17:50Z","timestamp":1760059070201,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T00:00:00Z","timestamp":1747440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Mental Health (NIMH)","award":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"],"award-info":[{"award-number":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"]}]},{"name":"Kavli Institute for Neuroscience at Yale University Kavli Postdoctoral Award for Academic Diversity","award":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"],"award-info":[{"award-number":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"]}]},{"name":"U.S. Department of Veterans Affairs","award":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"],"award-info":[{"award-number":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"]}]},{"name":"National Center for PTSD","award":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"],"award-info":[{"award-number":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"]}]},{"name":"SECIHTI","award":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"],"award-info":[{"award-number":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"]}]},{"name":"Juan Daniel Cruz-Castillo","award":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"],"award-info":[{"award-number":["1R01MH133621","1IK2CX002095-01A1","NIDA R21DA050160","DP1DA058737","CVU 888651","CVU 1043199"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u2019s clock (p = 0.015). Moreover, accelerated epigenetic age was correlated with chronological age (PedBE clock, p = 0.046), global functioning (Wu\u2019s 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\u2019s clock, \u03b2 = 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 (\u03b2 = 1.36, p = 0.03), as well as auditory (\u03b2 = 1.28, p = 0.04) and visual (\u03b2 = 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.<\/jats:p>","DOI":"10.3390\/genes16050591","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T04:48:18Z","timestamp":1747716498000},"page":"591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterizing the Social Epigenome in Mexican Patients with Early-Onset Psychosis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1191-2577","authenticated-orcid":false,"given":"David","family":"Ruiz-Ramos","sequence":"first","affiliation":[{"name":"Academic Division of Health Sciences, Ju\u00e1rez Autonomous University of Tabasco (UJAT), Villahermosa 86100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0390-8252","authenticated-orcid":false,"given":"Jos\u00e9 Jaime","family":"Mart\u00ednez-Maga\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT 06520, USA"},{"name":"VA Connecticut Healthcare System, West Haven, CT 06516, USA"},{"name":"U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, West Haven, CT 06516, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isela Esther","family":"Ju\u00e1rez-Rojop","sequence":"additional","affiliation":[{"name":"Academic Division of Health Sciences, Ju\u00e1rez Autonomous University of Tabasco (UJAT), Villahermosa 86100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5536-3173","authenticated-orcid":false,"given":"Germ\u00e1n Alberto","family":"Nolasco-Rosales","sequence":"additional","affiliation":[{"name":"Academic Division of Health Sciences, Ju\u00e1rez Autonomous University of Tabasco (UJAT), Villahermosa 86100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Sosa-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Dr. Juan N. Navarro Children\u2019s Psychiatric Hospital, National Commission on Mental Health and Addictions (CONASAMA), Ministry of Health, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Daniel","family":"Cruz-Castillo","sequence":"additional","affiliation":[{"name":"Academic Division of Health Sciences, Ju\u00e1rez Autonomous University of Tabasco (UJAT), Villahermosa 86100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josefa","family":"Cavazos","sequence":"additional","affiliation":[{"name":"Dr. Juan N. Navarro Children\u2019s Psychiatric Hospital, National Commission on Mental Health and Addictions (CONASAMA), Ministry of Health, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Callejas","sequence":"additional","affiliation":[{"name":"Dr. Juan N. Navarro Children\u2019s Psychiatric Hospital, National Commission on Mental Health and Addictions (CONASAMA), Ministry of Health, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Zavaleta-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Dr. Juan N. Navarro Children\u2019s Psychiatric Hospital, National Commission on Mental Health and Addictions (CONASAMA), Ministry of Health, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Antonio","family":"Zorrilla-Dosal","sequence":"additional","affiliation":[{"name":"Dr. Juan N. Navarro Children\u2019s Psychiatric Hospital, National Commission on Mental Health and Addictions (CONASAMA), Ministry of Health, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-6813","authenticated-orcid":false,"given":"Nuria","family":"Lanzagorta","sequence":"additional","affiliation":[{"name":"Carracci Medical Group, Department of Clinical Research, Mexico City 03740, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2494-0067","authenticated-orcid":false,"given":"Humberto","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Carracci Medical Group, Department of Clinical Research, Mexico City 03740, Mexico"},{"name":"Genomics Laboratory of Psychiatric, Neurodegenerative, and Addiction Disorders, National Institute of Genomic Medicine (INMEGEN), Ministry of Health, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janitza L.","family":"Montalvo-Ortiz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT 06520, USA"},{"name":"VA Connecticut Healthcare System, West Haven, CT 06516, USA"},{"name":"U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, West Haven, CT 06516, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Glahn","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA"},{"name":"Olin Neuropsychiatry Research Center, Institute of Living, Hartford, CT 06106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alma Delia","family":"Genis-Mendoza","sequence":"additional","affiliation":[{"name":"Dr. Juan N. Navarro Children\u2019s Psychiatric Hospital, National Commission on Mental Health and Addictions (CONASAMA), Ministry of Health, Mexico City 14080, Mexico"},{"name":"Genomics Laboratory of Psychiatric, Neurodegenerative, and Addiction Disorders, National Institute of Genomic Medicine (INMEGEN), Ministry of Health, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.jaac.2023.10.016","article-title":"Umbrella Review: Atlas of the Meta-Analytical Evidence of Early-Onset Psychosis","volume":"63","author":"Rodriguez","year":"2024","journal-title":"J. Am. Acad. Child Adolesc. 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