Accelerated aging in the brain, epigenetic aging in blood, and polygenic risk for schizophrenia

Jalmar Teeuw*, Anil P.S. Ori, Rachel M. Brouwer, Sonja M.C. de Zwarte, Hugo G. Schnack, Hilleke E. Hulshoff Pol, Roel A. Ophoff

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Schizophrenia patients show signs of accelerated aging in cognitive and physiological domains. Both schizophrenia and accelerated aging, as measured by MRI brain images and epigenetic clocks, are correlated with increased mortality. However, the association between these aging measures have not yet been studied in schizophrenia patients. In schizophrenia patients and healthy subjects, accelerated aging was assessed in brain tissue using a longitudinal MRI (N = 715 scans; mean scan interval 3.4 year) and in blood using two epigenetic age clocks (N = 172). Differences (‘gaps’) between estimated ages and chronological ages were calculated, as well as the acceleration rate of brain aging. The correlations between these aging measures as well as with polygenic risk scores for schizophrenia (PRS; N = 394) were investigated. Brain aging and epigenetic aging were not significantly correlated. Polygenic risk for schizophrenia was significantly correlated with brain age gap, brain age acceleration rate, and negatively correlated with DNAmAge gap, but not with PhenoAge gap. However, after controlling for disease status and multiple comparisons correction, these effects were no longer significant. Our results imply that the (accelerated) aging observed in the brain and blood reflect distinct biological processes. Our findings will require replication in a larger cohort.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalSchizophrenia Research
Early online date18 May 2021
Publication statusPublished - May 2021

Bibliographical note

Funding Information:
This work was supported by the Gravitation program of the Dutch Ministry of Education, culture, and Science and the Netherlands Organization for Scientific Research ( ; Consortium on Individual Development (CID) NWO grant number 024.001.003 subproject to H.H., and by NWO 51.02.061 to H.H., NWO 51.02.062 to D.B., NWO-NIHC Programs of excellence 433-09-220 to H.H., NWO-MagW 480-04-004 to D.B., and NWO/SPI 56-464-14192 to D.B.); the European Research Council ( ; ERC-230374 to D.B.); and Utrecht University (; High Potential Grant to H.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright: © 2021 The Authors


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