Epigenetic clock analysis of blood samples from Japanese schizophrenia patients

Satoshi Okazaki,Tadasu Horai,Akitoyo Hishimoto,Shuken Boku,Ikuo Otsuka,Kentaro Mouri,Shusuke Numata,Tetsuro Ohmori,Ichiro Sora

doi:10.1038/s41537-019-0072-1

Satoshi Okazaki, Tadasu Horai + Show 7 more

Open Access

https://doi.org/10.1038/s41537-019-0072-1

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Journal: NPJ schizophrenia	Publication Date: Feb 27, 2019
Citations: 33	License type: open-access

Affiliation: Kobe University, Tokushima University

Abstract

The accelerated aging hypothesis of schizophrenia (SCZ) has been proposed. DNA methylation profiles were developed for determining “epigenetic age.” Here, we assessed intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA, respectively) in SCZ. We examined two independent cohorts of Japanese ancestry. The first cohort consisted of 80 patients with SCZ under long-term or repeated hospitalization and 40 controls, with the economical DNA pooling technique. The second cohort consisted of 24 medication-free patients with SCZ and 23 controls. Blood of SCZ subjects exhibited decreased EEAA in the first cohort (p = 0.0162), but not in the second cohort. IEAA did not differ in either cohort. We performed replication analyses using publicly available datasets from European ancestry (three blood and one brain datasets). One blood dataset showed increased EEAA in SCZ (p = 0.0228). Overall, our results provide evidence for decreased EEAA in SCZ associated with hospitalization in the Japanese population.

Highlights

Schizophrenia (SCZ) is a chronic and disabling psychiatric illness affecting ~1% of the general population.[1]
We considered three measures of epigenetic age acceleration: universal epigenetic age acceleration (AgeAccel), intrinsic epigenetic age acceleration (IEAA), and EEAA, as detailed in Methods
AgeAccel showed a significant correlation with IEAA and EEAA

Summary

Introduction

Schizophrenia (SCZ) is a chronic and disabling psychiatric illness affecting ~1% of the general population.[1] SCZ is associated with premature age-related phenotypes throughout the body. High mortality is observed in SCZ, resulting in a life expectancy of approximately 20 years below that of the general population.[10] Most of the excess mortality has been attributed to natural causes such as cardiovascular and respiratory diseases, mortality rates of unnatural causes such as suicide and accidental death are higher in patients with SCZ.[11] Both endogenous (such as genetic risk) and environmental (such as lifestyle and health care access) factors are suggested to contribute to premature mortality in SCZ. The accelerated aging hypothesis of SCZ has been advanced as a putative explanation for these observations

Methods

Results

Conclusion