Epigenetic signatures of different types of childhood maltreatment in a high-risk sample: a preregistered replication study

Childhood maltreatment (CM) has long-lasting effects on physical and mental health with CM type specific effects being reported. Epigenetic processes, like deoxyribonucleic acid methylation (DNAm), might mediate this link, and CM types might be linked to differential alterations in DNAm. While a study by Cecil et al. [1] suggests that different forms of CM share common but also exhibit distinct epigenetic signatures, it is unclear whether these results are generalizable to other high-risk samples.

The aim of this preregistered study was to replicate the study of Cecil and colleagues [1] in a sample of N = 116 previously out-of-home placed young adults (32% women, age mean = 26.38, SD = 3.49). Participants completed the Childhood Trauma Questionnaire - Short Form (CTQ-SF), DNA was extracted from whole blood and DNAm was assayed using the Illumina Infinium MethylationEPIC BeadChip Microarray. Using state-of the-art processing pipelines, we failed to replicate the original finding of common and shared epigenetic signatures by CM type.

When using a pipeline that was closely matched to the original study, we found that DNAm of cg07032930 was significantly linked to emotional neglect, but in the reverse direction as in the original report. Overall, replication rates per CM subtype were only modest. These findings highlight challenges in independently replicating reported epigenetic associations in high-risk samples and underscore the importance of replication attempts in the field of behavioral epigenetics.

Further research is needed to clarify the robustness and specificity of DNAm signatures linked to distinct CM types. We thank the authors of the original publication (https://doi.org/10.1016/j.jpsychires.2016.09.010), especially Charlotte Cecil, PhD, for their collaborative support. The MAZ. study and the JAEL follow-up study were funded by the Swiss Ministry of Justice (PI: MS).

The neurobiological add-on study LOCO and its extension LOC-o-met was funded by the Gertrud Thalmann Fonds of the University Psychiatric Hospitals Basel (PI: MS and DB). MM was employed via a DFG/SNSF Lead Agency Grant (DFG: CL 878/2-1; SNSF: 204033). DB was supported by the Research Fund for Excellent Junior Researcher of the University of Basel for the study ‘Childhood Trauma - Questioning, understanding, exploring, seeing, testing (CT-Quest)’.

PJ was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC-2049/2 – 390688087. Open access funding provided by University of Basel. Child and Adolescent Psychiatric Research Department, University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland Maria Meier, Laura Gurri, Katharina Beck, Delfine d’Huart, Cyril Boonmann, Christina Stadler, Marc Schmid, David Bürgin & Eva Unternaehrer Department of Psychology, University of Konstanz, Konstanz, Germany Department of Youth Forensic, University Psychiatric Clinics Basel (UPK), Basel, Switzerland Charité – Universitätsmedizin Berlin, Berlin, Germany Department of Child and Adolescent Psychiatry (LUMC Curium), Leiden University Medical Center, Leiden, The Netherlands Jacobs Center for Productive Youth Development, University of Zurich, Zurich, Switzerland The authors declare no competing interests.