The pediatric buccal epigenetic clock identifies significant ageing acceleration in children with internalizing disorder and maltreatment exposure
Autor: | Katja Dittrich, Felix Dammering, Darina Czamara, Sibylle Winter, Jade Martins, Christine Heim, Sonja Entringer, Monika Rex-Haffner, Karin de Punder, Elisabeth B. Binder, Claudia Buss, Judith Overfeld |
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Rok vydání: | 2021 |
Předmět: |
Neurophysiology and neuropsychology
Physiology Internalizing disorder Neurosciences. Biological psychiatry. Neuropsychiatry Early development Child Abuse and Neglect Research Biochemistry Cellular and Molecular Neuroscience Endocrinology Clinical Research Genetics Maltreatment Medicine Early childhood Epigenetics Original Research Article RC346-429 Molecular Biology Glucocorticoids Violence Research Pediatric Psychopathology Endocrine and Autonomic Systems business.industry QP351-495 Epigenetic ageing Targeted interventions Moderation medicine.disease Ageing DNA methylation Neurology. Diseases of the nervous system business RC321-571 Clinical psychology |
Zdroj: | Neurobiology of Stress Neurobiology of Stress, Vol 15, Iss, Pp 100394-(2021) |
ISSN: | 2352-2895 |
Popis: | BackgroundStudies 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.MethodDNA 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.ResultsChildren with internalizing disorder exhibited significant acceleration of epigenetic ageing as compared to children without internalizing disorder (F1,147=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.ConclusionUsing 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. |
Databáze: | OpenAIRE |
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