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

<b>Background:</b> 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. <b>Objectives:</b> We characterized the sociodemographic and clinical characteristics, as well as genome-wide epigenetic markers, in Mexican patients with EOP. <b>Methods:</b> We estimated epigenetic age, performed an epigenome-wide association study, and finally developed an epigenetic risk score (MRS) to predict manifestations of psychosis. <b>Results:</b> We found that patients with EOP have a higher epigenetic age using Wu's clock (<i>p</i> = 0.015). Moreover, accelerated epigenetic age was correlated with chronological age (PedBE clock, <i>p</i> = 0.046), global functioning (Wu's clock, <i>p</i> = 0.027), and psychiatric admissions (DNAmTL, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 0.03), as well as auditory (β = 1.28, <i>p</i> = 0.04) and visual (β = 1.22, <i>p</i> = 0.04) hallucinations. <b>Conclusions:</b> 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.