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

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 (9gaps9) 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.