Adverse childhood experiences, epigenetics and telomere length variation in childhood and beyond: a systematic review of the literature

A systematic review following PRISMA guidelines was conducted to answer the question: What epigenetic, telomeric and associated biological changes are associated with exposure to adverse childhood experiences (ACEs) in the under 12s? Using PRISMA guidelines, appropriate databases were searched. 190 papers were returned with 38 articles fully reviewed. Articles were each independently quality rated by two authors using the Crowe Critical Appraisal Tool and data were extracted. Of the 38 articles, 23 were rated as very high quality. Most study participants were adults (n = 7769) with n = 727 child participants. Only seven of the very/high-quality studies were prospective and involved children. Methylation was the most studied method of epigenetic modification. There is some evidence supporting epigenetic modification of certain markers in participants exposed to ACEs measured in adulthood. Research is lacking on non-coding aspects of the epigenome and on coding aspects other than DNA methylation. There is some evidence of a more powerful effect on telomere length if physical neglect was involved. Much further work is required to model biological and psychological effects of epigenetic changes during childhood using prospective study designs. The effect of ACEs on the cellular ageing process during childhood is inadequately investigated and relies solely on measure of telomere length. Future research suggestions are proposed

Molecular characterisation of murine Nfe2l1

The conservation of some developmental processes amongst species as diverse as Drosophila, C.elegans, man and mouse has been one of the most exciting scientific discoveries in recent years. The initial premise for the thesis was the isolation of a mouse cDNA fragment, 8dl, which had striking similarity to a Drosophila protein, CNC. cnc encodes a bZIP transcription factor and is thought to be involved in head specification. The initial aims were therefore to establish if the murine homologue (latterly known as Nfe2l1) of CNC had been isolated, and what, if any, was its role in murine development. The full length sequence of Nfe2l1 was determined and its chromosomal localisation in both mouse and man identified. The expression pattern of Nfe2l1 throughout murine development was studied, and although it was ubiquitous throughout the developmental stages studied, specific sites of developmental upregulation could be identified. Nfe2l1 is unlikely to be the murine homologue of CNC, but rather, one member of a family of CNC-related proteins that form a subclass of the bZIP transcription factor family. The evidence from both the work presented in this thesis and the published studies suggests that Nfe2l1 is likely to have a role in murine development. In addition, a novel human family member, NFM, has been identified by database screening with NFE2L1. Several cDNAs have been isolated and partially characterised by sequence and northern analyses, and NFM-positive human PACs have permitted FISH localisation studies

Repeated dexamphetamine treatment alters the dopaminergic system and increases the phMRI response to methylphenidate

EU grant to LR, PJL, WG and FD (ERA-NET PrioMedChild, a joined call of Priority Medicines for Children, grant no. 40-41800-98-026