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This page is an AI-assisted Turkish summary of the study presented at the 26th World Congress of Psychiatry. The study belongs to the presenting authors; please refer to the original source when citing it.

EV0647

Disentangling epigenetic aging in psychiatric disorders: a tissue-specific multilevel meta-analysis across clock generations

DISENTANGLING EPIGENETIC AGING IN PSYCHIATRIC DISORDERS: A TISSUE-SPECIFIC MULTILEVEL META-ANALYSIS ACROSS DIFFERENT CLOCK GENERATIONS.

Accelerated epigenetic aging measured using later-generation epigenetic clocks in blood tissue is significant particularly in internalizing disorders, whereas no significant findings were detected in brain tissue.

The aim was to synthesize current evidence on epigenetic aging in psychiatric disorders through a systematic review and multilevel meta-analysis, and to investigate heterogeneity across tissues (blood and brain), ancestry, and clock generations using meta-regression. Of 12,399 records identified in PubMed, Web of Science, and Scopus, 7,232 were screened after duplicates were removed, 76 full texts were assessed, and 30 studies were included in the review; the effect size measure was Hedges’ g, and the multilevel model incorporated robust variance estimation (RVE), a Satterthwaite degrees-of-freedom correction, and false discovery rate (FDR) adjustment. Diagnoses were grouped into transdiagnostic factors based on genomic correlations (internalizing: major depressive disorder, MDD, and posttraumatic stress disorder, PTSD; and schizophrenia and bipolar disorder, SCZ/BD). In blood tissue, overall results were significant for MDD, with an estimate of 0.173 (standard error 0.055; p=0.02), PTSD, at 0.220 (0.069; p=0.016), and the internalizing factor, at 0.207 (0.043; p=0.0004), whereas results for SCZ, at 0.100 (0.104; p=0.402), BD, at 0.341 (0.350; p=0.433), and SCZ/BD, at 0.161 (0.126; p=0.247), were not significant; in brain tissue, no significant results were found for either individual diagnoses or transdiagnostic factors. By clock generation, blood-based estimates for internalizing disorders were g=0.16 (first generation, p_FDR<0.01), 0.25 (second generation), and 0.30 (third generation, both p_FDR<0.001); for SCZ/BD, estimates were g=-0.01 (first generation, nonsignificant), 0.25 (second generation), and 0.38 (third generation, p_FDR<0.05). In multivariable meta-regression, with first-generation clocks as the reference, second-generation clocks yielded higher effects of 0.20 [0.10, 0.30], and third-generation clocks yielded higher effects of 0.28 [0.14, 0.42]; with second-generation clocks as the reference, the baseline adjusted estimate for internalizing disorders became significant at 0.28 [0.13, 0.43], while the non-European ancestry variable was nonsignificant in both models (0.01 [-0.20, 0.23]). Subgroup analysis identified a significant difference in epigenetic aging between European-ancestry and multiethnic cohorts (g=0.293, p=0.031). In conclusion, later, second- and third-generation epigenetic clocks serve as robust peripheral biomarkers for internalizing disorders; the absence of findings in brain tissue points to the tissue-specific nature of DNA methylation rather than an absence of central nervous system aging and warrants further research.

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