Beyond genotype: Neuroimaging epigenetics of threat and reward circuitry in humans to understand risk for psychopathology

Lead Research Organisation: University of Birmingham
Department Name: School of Psychology

Abstract

The overarching question of this PhD project is: How do early life experience, genes, brain activity, and behaviour relate to one another? To address this question, the proposed PhD project will use a neuroimaging epigenetic approach to go beyond the genome and examine the role of epigenetic modifications in the association between genetic markers and variability in brain activity that are associated with individual differences in behaviour and risk for psychopathology. As such, it has recently been proposed that the neuroimaging epigenetic approach is the logical next step in neuroimaging genetics 4. This PhD project will use data collected from a large F7 multisite European study focussing on male and female youths aged 9-18 years (www.femnat-cd.eu). Specifically, for the first time the association between childhood maltreatment, DNA methylation, fMRI BOLD response/connectivity, and measures of externalising and internalising disorders will be examined in youths. Patterns of DNA methylation are currently being obtained from blood for a number of genes implicated in the brain's threat and reward circuitries. The fMRI analyses will focus on a network of cortical and subcortical brain regions central to threat and reward processing and with dense serotonin, dopamine or oxytocin receptors and transporters. By systematically examining the association between childhood maltreatment, DNA methylation, and brain function/connectivity, it is hoped that this project will further our understanding of the molecular mechanisms of risk for psychopathology.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1898526 Studentship BB/M01116X/1 02/10/2017 30/09/2021 Elizabeth Farrow
 
Description Deutscher Akademischer Austauschdienst Research Grant - Short term Grant
Amount € 3,000 (EUR)
Organisation German Academic Exchange Service (DAAD) 
Sector Academic/University
Country United States
Start 07/2020 
End 09/2020
 
Description FEMNAT-CD 
Organisation Goethe University Frankfurt
Country Germany 
Sector Academic/University 
PI Contribution The lab I am working in at the University of Birmingham (director: Dr Stephane De Brito) was one of the key sites used for collecting MRI, clinical and behavioural data during the longitudinal FEMNAT-CD study. Dr De Brito is one of the founding members of the project, and a key part of the FEMNAT-CD steering committee. My personal role has been collating and organising data collected at multiple sites across Europe into a single database including all key in a standardised form. In my PhD research thus far,I have completed pre-processing and analysis of both structural and functional MRI data for a sub-sample of female participants. I have also been working with epigenetic (genome-wide DNA methylation) data from these participants (from saliva DNA samples), and I am currently integrating the findings obtained from neuro-imaging and genetic data to attempt to understand more about the biological mechanisms which underpin the development of conduct disorder and callous-unemotional traits in adolescent females.
Collaborator Contribution The FemNAT-CD Consortium consists of 17 partner Institutions across Europe. These institutions are listed below: 1)Project Coordinator: GU Frankfurt am Main 2)Uniklinikum Aachen 3)Stichting VU-VUMC 4)University of Southampton 5)Universität Basel 6)Universität Heidelberg 7)University of Birmingham 8)Trinity College Dublin 9)Universität Regensburg 10)Fundació Docència I Recerca Mútua Terrassa (UTB) 11)Fundacion Vasca De Innovacion E Investigacion Sanitarias (BIOEF/Osakidetza) 12)Szegedi Tudomanyegyetem 13)National and Kapodistrian University of Athens 14)Genewake GmbH 15)Varionostic GmbH 16)DAACRO GmbH & Co KG 17)ARTTIC S.A.S. (ART) To facilitate the organisation and management of the various aspects of this project, FemNAT-CD is structured in 10 work packages (WPs). Different partner instituations were involved in different WPs, depending on their facilities and expertise. Please refer to the project website for the full description of these WPs and the partner institutions involved in their implementation http://www.femnat-cd.eu/project/index.htm.
Impact Please see the project Final Report Summary at https://cordis.europa.eu/project/id/602407/reporting An up-to-date list of publications associated with the FEMNAT-CD Consortium is also available online via researchgate.
Start Year 2013