Meta-analyses of epigenetic age acceleration and GrimAge components of schizophrenia or first-episode psychosis

Abstract

Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia is ≥10 years shorter than that in the general population because of the higher risk of other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values of aging-related proteins (GrimAge and GrimAge2 components) have been analyzed in multiple diseases. However, no studies have investigated up to GrimAge and GrimAge2 components between patients with schizophrenia and controls. Therefore, we aimed to conduct multiple regression analyses to investigate the association between schizophrenia and epigenetic age accelerations and GrimAge and GrimAge2 components in seven cohorts. Furthermore, we included patients with first-episode psychosis whose illness duration was often shorter than schizophrenia in our analysis. We integrated these results with meta-analyses, noting the acceleration of GrimAge, GrimAge2, and DunedinPACE, and increase in adrenomedullin, beta-2 microglobulin, cystatin C, and plasminogen activation inhibitor-1 levels, in patients with schizophrenia or first-episode psychosis. These results corroborated the finding that patients with schizophrenia had an increased risk of diabetes, cardiovascular disease, and cognitive dysfunction from a biological perspective. Patients with schizophrenia and first-episode psychosis showed differences in the results when compared with controls. Such analyses may lead to the development of novel therapeutic targets to patients with schizophrenia or relevant diseases from the perspective of aging in the future.

Fig. 1. The forest plots on the age acceleration of note from meta-analyses for seven cohorts comparing patients with schizophrenia or first-episode psychosis, with controls, in the first regression model.

A AgeAccelPheno, B AgeAccelGrim, C AgeAccelGrim2, D DNAmTLAdjAge, and (E) DunedinPACE. Figure creation and statistical calculations are performed using the R package metafor. DNAm DNA methylation, DNAmTLAdjAge age-adjusted estimate of DNA methylation-based telomere length.

Fig. 2. The forest plots on the GrimAge components of note from meta-analyses for seven cohorts comparing patients with schizophrenia or first-episode psychosis, with controls, in the first regression model.

A DNAmADM, B DNAmB2M, C DNAmCystatinC, and (D) DNAmPAI1. Figure creation and statistical calculations are performed using the R package metafor. Abbreviations: ADM adrenomedullin, B2M beta-2 microglobulin, DNAm DNA methylation, PAI1 plasminogen activation inhibitor-1.