Cell-type-specific ageing effects in the human OFC and implication for psychiatric disease

We evaluated biological aging using two epigenetic clocks (Horvath’s multi-tissue clock and CorticalClock (Shireby et al.)Brain 2020) calculated from DNA methylation measured in human post-mortem brain (orbitofrontal cortex; BA11) in a trans-diagnostic psychiatric sample including healthy controls. Epigenome-wide DNA methylation profiling was performed with the Illumina Infinium MethylationEPIC BeadChip (version 1.0; Illumina, San Diego, CA, USA) according to manufacturer’s guidelines. The total cohort consisted of 91 individuals. Five individuals were run in duplicate (as internal control). Individuals were either diagnosed a psychiatric disease (1) or psychiatrically healthy (0). Independent of the epigenetic clock used, we did not find evidence for accelerated epigenetic aging in individuals diagnosed with a psychiatric disorder. The study sample (N=91, 5 additional technical replicates) included participants from NSW Brain Tissue Resource Centre in Sydney, Australia. DNA from fresh-frozen postmortem tissue of the orbitofrontal cortex (BA11) was extracted and underwent bisulfite conversion. The bisulfite-converted DNA was used to assess epigenome-wide DNAm via Illumina Infinium MethylationEPIC BeadChip v1.0 (Illumina, San Diego, CA, USA).