The pediatric buccal epigenetic clock identifies significant ageing acceleration in children with internalizing disorder and maltreatment exposure.

Autor:	Dammering F; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany., Martins J; Dept. of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany., Dittrich K; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Dept. of Child & Adolescent Psychiatry, Psychotherapy, and Psychosomatics, Berlin, Germany., Czamara D; Dept. of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany., Rex-Haffner M; Dept. of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany., Overfeld J; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany., de Punder K; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany., Buss C; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.; University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, USA., Entringer S; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.; University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, USA., Winter SM; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Dept. of Child & Adolescent Psychiatry, Psychotherapy, and Psychosomatics, Berlin, Germany., Binder EB; Dept. of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany., Heim C; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.; Dept. of Biobehavioral Health, The Pennsylvania State University, University Park, PA, USA.
Jazyk:	angličtina
Zdroj:	Neurobiology of stress [Neurobiol Stress] 2021 Sep 11; Vol. 15, pp. 100394. Date of Electronic Publication: 2021 Sep 11 (Print Publication: 2021).
DOI:	10.1016/j.ynstr.2021.100394
Abstrakt:	Background: Studies reporting accelerated ageing in children with affective disorders or maltreatment exposure have relied on algorithms for estimating epigenetic age derived from adult samples. These algorithms have limited validity for epigenetic age estimation during early development. We here use a pediatric buccal epigenetic (PedBE) clock to predict DNA methylation-based ageing deviation in children with and without internalizing disorder and assess the moderating effect of maltreatment exposure. We further conduct a gene set enrichment analysis to assess the contribution of glucocorticoid signaling to PedBE clock-based results. Method: DNA was isolated from saliva of 158 children [73 girls, 85 boys; mean age (SD) = 4.25 (0.8) years] including children with internalizing disorder and maltreatment exposure. Epigenetic age was estimated based on DNA methylation across 94 CpGs of the PedBE clock. Residuals of epigenetic age regressed against chronological age were contrasted between children with and without internalizing disorder. Maltreatment was coded in 3 severity levels and entered in a moderation model. Genome-wide dexamethasone-responsive CpGs were derived from an independent sample and enrichment of these CpGs within the PedBE clock was identified. Results: Children with internalizing disorder exhibited significant acceleration of epigenetic ageing as compared to children without internalizing disorder (F 1,147  = 6.67, p  = .011). This association was significantly moderated by maltreatment severity (b = 0.49, 95% CI [0.073, 0.909], t = 2.322, p  = .022). Children with internalizing disorder who had experienced maltreatment exhibited ageing acceleration relative to children with no internalizing disorder (1-2 categories: b = 0.50, 95% CI [0.170, 0.821], t = 3.008, p  = .003; 3 or more categories: b = 0.99, 95% CI [0.380, 1.593], t = 3.215, p = .002). Children with internalizing disorder who were not exposed to maltreatment did not show epigenetic ageing acceleration. There was significant enrichment of dexamethasone-responsive CpGs within the PedBE clock (OR = 4.36, p  = 1.65*10-6). Among the 94 CpGs of the PedBE clock, 18 (19%) were responsive to dexamethasone. Conclusion: Using the novel PedBE clock, we show that internalizing disorder is associated with accelerated epigenetic ageing in early childhood. This association is moderated by maltreatment severity and may, in part, be driven by glucocorticoids. Identifying developmental drivers of accelerated epigenetic ageing after maltreatment will be critical to devise early targeted interventions. Competing Interests: None. (© 2021 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu