Epigenetics and ADHD.

There is robust evidence of genetic susceptibility to Attention-Deficit Hyperactivity Disorder (ADHD); however, there still remains significant variability that is not attributable to genetic factors. The emerging field of epigenetics is beginning to reveal how genotypic expression can be mediated by an array of variables including external environmental exposure, inter-individual developmental variation, and by the genome itself. Epigenetic modification plays a central role in neurobiological and developmental processes, and disturbances to these processes can have implications for a range of mental health problems. Although the field is still in its early days, this chapter will discuss the current standing of epigenetic research into ADHD. Firstly, key relevant epigenetic processes will be discussed. This will be followed by an overview of the key findings to date investigating the role of epigenetics in ADHD. Human studies have included the theory-driven approach of candidate-gene studies (CGS), as well as the increasingly popular exploratory approach of epigenome-wide association studies (EWAS). Overall, the findings are heterogeneous. However, it is possible that with more longitudinal studies and better characterised cohorts, both predictive and protective links between epigenetic processes and ADHD will be revealed.

A comparison of epithelial cell content of oral samples estimated using cytology and DNA methylation.

Saliva and buccal samples are popular for epigenome wide association studies (EWAS) due to their ease of collection compared and their ability to sample a different cell lineage compared to blood. As these samples contain a mix of white blood cells and buccal epithelial cells that can vary within a population, this cellular heterogeneity may confound EWAS. This has been addressed by including cellular heterogeneity obtained through cytology at the time of collection or by using cellular deconvolution algorithms built on epigenetic data from specific cell types. However, to our knowledge, the two methods have not yet been compared. Here we show that the two methods are highly correlated in saliva and buccal samples (R = 0.84, P < 0.0001) by comparing data generated from cytological staining and Infinium MethylationEPIC arrays and the EpiDISH deconvolution algorithm from buccal and saliva samples collected from twenty adults. In addition, by using an expanded dataset from both sample types, we confirmed our previous finding that age has strong, non-linear negative correlation with epithelial cell proportion in both sample types. However, children and adults showed a large within-population variation in cellular heterogeneity. Our results validate the use of the EpiDISH algorithm in estimating the effect of cellular heterogeneity in EWAS and showed DNA methylation generally underestimates the epithelial cell content obtained from cytology.

Parental Preconception Exposures to Outdoor Neighbourhood Environments and Adverse Birth Outcomes: A Protocol for a Scoping Review and Evidence Map.

Parental preconception exposures to built and natural outdoor environments could influence pregnancy and birth outcomes either directly, or via a range of health-related behaviours and conditions. However, there is no existing review summarising the evidence linking natural and built characteristics, such as air and noise pollution, walkability, greenness with pregnancy and birth outcomes. Therefore, the planned scoping review aims to collate and map the published literature on parental preconception exposures to built and natural outdoor environments and adverse pregnancy and birth outcomes. We will search electronic databases (MEDLINE, EMBASE, Scopus) to identify studies for inclusion. Studies will be included if they empirically assess the relationship between maternal and paternal preconception exposures to physical natural and built environment features that occur outdoors in the residential neighbourhood and adverse pregnancy and birth outcomes. Two reviewers will independently screen titles and abstracts, and then the full text. Data extraction and assessment of study quality will be performed by one researcher and checked by a second researcher. Results will be summarised in a narrative synthesis, with additional summaries presented as tables and figures. The scoping review will be disseminated via a peer-reviewed publication, at academic conferences, and published on a website.