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Na Zhan¹, Perry B M Leung^1,2, Yuanxin Zhong^1,3,4,5

¹Department of Psychiatry, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Translational psychiatry

|February 10, 2026

Resumen

Este estudio identifica nuevos patrones de metilación del ADN en la esquizofrenia de inicio temprano (EOS) dentro de la población china. Estos cambios epigenéticos están relacionados con el desarrollo neurológico y pueden revelar nuevos objetivos terapéuticos para este trastorno psiquiátrico.

Área de la Ciencia:

La neurociencia es la neurociencia.
Genética La genética.
La epigenética es la epigenética.

Sus antecedentes:

La esquizofrenia presenta diversas trayectorias influenciadas por la edad de aparición (AAO), con la esquizofrenia de aparición temprana (EOS) exhibiendo resultados más pobres.
Los mecanismos epigenéticos como la metilación del ADN son poco estudiados en EOS, particularmente en la población china.

Objetivo del estudio:

Para investigar los patrones de metilación diferencial del ADN en la esquizofrenia de inicio temprano (EOS) en comparación con la esquizofrenia de inicio adulto (AOS) en una cohorte china.
Para identificar nuevos marcadores epigenéticos y vías biológicas asociadas con la patogénesis de EOS.

Principales métodos:

Se analizó el ADN de la sangre periférica de 120 pacientes con esquizofrenia (49 EOS, 71 AOS) utilizando la matriz Infinium MethylationEPIC v2.0.
Se realizaron análisis de metilación diferencial comparando EOS vs. AOS y AAO continuo, ajustando las covariables.
Se utilizaron umbrales de significación estrictos (p < 5x10^-5) y anotación genética para los DMP identificados.

Principales resultados:

Se identificaron 49 posiciones diferencialmente metiladas (DMP) para EOS-AOS y 126 DMP para AAO continuo.
DMPs anotados vinculados a los loci conocidos de la esquizofrenia (por ejemplo, ORMDL1) y nuevos genes implicados en el desarrollo neurológico y la cognición (por ejemplo, AKAP8L).
El análisis de enriquecimiento destacó las vías en la señalización de la quinasa, la regulación del ciclo celular y las vías de microARN involucradas en la apoptosis y la oncogénesis.

Conclusiones:

Se revelaron nuevas firmas de metilación del ADN asociadas con EOS en la población china.
Identificó las vías biológicas clave que podrían estar subyacentes a la patogénesis de la EOS, ofreciendo información sobre los aspectos del desarrollo neurológico del trastorno.

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