Childhood adversity correlates with stable changes in DNA methylation trajectories in children and converges with epigenetic signatures of prenatal stress
| Autor: | Felix Dammering, Peggy Dörr, Christine Heim, Darina Czamara, Sibylle Winter, Elisabeth B. Binder, Claudia Buss, Judith Overfeld, Sonja Entringer, Jade Martins, Susann Sauer, Monika Rex-Haffner, Karin de Punder, Andrea Knop, Katja Dittrich |
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| Rok vydání: | 2021 |
| Předmět: |
Physiology
Biochemistry Substance Misuse 0302 clinical medicine Endocrinology Prenatal exposure Medicine 2.1 Biological and endogenous factors Original Research Article Aetiology Violence Research Pediatric QP351-495 Early-life adversity Mental Health Cohort Epigenetics social and economic factors RC321-571 Neurophysiology and neuropsychology Exposome Pediatric Research Initiative Neurosciences. Biological psychiatry. Neuropsychiatry Child Abuse and Neglect Research Stress Basic Behavioral and Social Science 03 medical and health sciences Cellular and Molecular Neuroscience Clinical Research 2.3 Psychological Behavioral and Social Science Genetics Conditions Affecting the Embryonic and Fetal Periods Risk factor RC346-429 Molecular Biology Endocrine and Autonomic Systems business.industry Prevention Human Genome dNaM Epigenome 030227 psychiatry Differentially methylated regions Good Health and Well Being Prenatal stress Risk factors Observational study Neurology. Diseases of the nervous system business 030217 neurology & neurosurgery Demography |
| Zdroj: | Neurobiology of Stress, Vol 15, Iss, Pp 100336-(2021) Neurobiology of Stress |
| Popis: | Childhood maltreatment (CM) is an established major risk factor for a number of negative health outcomes later in life. While epigenetic mechanisms, such as DNA methylation (DNAm), have been proposed as a means of embedding this environmental risk factor, little is known about its timing and trajectory, especially in very young children. It is also not clear whether additional environmental adversities, often experienced by these children, converge on similar DNAm changes. Here, we calculated a cumulative adversity score, which additionally to CM includes socioeconomic status (SES), other life events, parental psychopathology and epigenetic biomarkers of prenatal smoking and alcohol consumption. We investigated the effects of CM alone as well as the adversity score on longitudinal DNAm trajectories in the Berlin Longitudinal Child Study. This is a cohort of 173 children aged 3-5 years at baseline of whom 86 were exposed to CM. These children were followed-up for 2 years with extensive psychometric and biological assessments as well as saliva collection at 5 time points providing genome-wide DNAm levels. Overall, only a few DNAm patterns were stable over this timeframe, but less than 10 DNAm regions showed significant changes. At baseline, neither CM nor the adversity score associated with DNAm changes. However, in 6 differentially methylated regions (DMRs), CM and the adversity score significantly moderated DNAm trajectories over time. A number of these DMRs have previously been associated with adverse prenatal exposures. In our study, children exposed to CM also presented with epigenetic signatures indicative of increased prenatal exposure to tobacco and alcohol, as compared to non-CM exposed children. These epigenetic signatures of prenatal exposure strongly correlate with DNAm regions associated with CM and the adversity score. Finally, weighted correlation network analysis revealed a module of CpGs exclusively associated with CM. While our study identifies DNAm loci specifically associated with CM, especially within long non-coding RNAs, the majority of associations were found with the adversity score with convergent association with indicators of adverse prenatal exposures. This study highlights the importance of mapping not only of the epigenome but also the exposome and extending the observational timeframe to well before birth. |
| Databáze: | OpenAIRE |
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