Epigenetic clock analysis of blood samples in drug-naive first-episode schizophrenia patients

Abstract

Background: Schizophrenia (SCZ) is a severe and chronic psychiatric disorder with premature age-related physiological changes. However, numerous previous studies examined the epigenetic age acceleration in SCZ patients and yielded inconclusive results. In this study, we propose to explore the epigenetic age acceleration in drug-naive first-episode SCZ (FSCZ) patients and investigate whether epigenetic age acceleration is associated with antipsychotic treatment, psychotic symptoms, cognition, and subcortical volumes.

Methods: We assessed the epigenetic age in 38 drug-naive FSCZ patients and 38 healthy controls by using three independent clocks, including Horvath, Hannum and Levine algorithms. The epigenetic age measurements in SCZ patients were repeated after receiving 8 weeks risperidone monotherapy.

Results: Our findings showed significantly positive correlations between epigenetic ages assessed by three clocks and chronological age in both FSCZ patients and healthy controls. Compared with healthy controls, drug-naive FSCZ patients have a significant epigenetic age deceleration in Horvath clock (p = 0.01), but not in Hannum clock (p = 0.07) and Levine clock (p = 0.43). The epigenetic ages of Hannum clock (p = 0.002) and Levine clock (p = 0.01) were significantly accelerated in SCZ patients after 8-week risperidone treatment. However, no significant associations between epigenetic age acceleration and psychotic symptoms, cognitive function, as well as subcortical volumes were observed in FSCZ patients.

Conclusion: These results demonstrate that distinct epigenetic clocks are sensitive to different aspects of aging process. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings.

Keywords: Antipsychotic treatment; DNA methylation; Epigenetic age; Schizophrenia.

Fig. 1

Epigenetic age analyses in drug-naive first-episode schizophrenia (SCZ) patients and healthy controls. A Significant Pearson’s correlations between epigenetic age and chronological age in SCZ patients at baseline (red) and after 8 weeks treatment (blue), and healthy controls (black). Each panel of the figure shows scatter plots of epigenetic age (y-axis) against chronological age (x-axis) in whole blood sample measured by Horvath, Hannum, and Levine epigenetic clocks. B Comparison of epigenetic age acceleration between drug-naive first-episode SCZ patients and healthy controls. Between-group difference of epigenetic age acceleration measured by Horvath, Hannum, and Levine epigenetic clocks were tested by regression analyses adjusting for age, sex, and tobacco use. C Antipsychotic effects on epigenetic age acceleration in drug-naive first-episode SCZ patients. The changes of epigenetic age acceleration in drug-naive first-episode SCZ patients before and after 8-week risperidone treatment were tested with Paired samples t-test. FSCZ: drug-naive first-episode schizophrenia, TSCZ: 8-week antipsychotics treated drug-naive first-episode schizophrenia