a. About psychiatric epigenetics
Sequencing the genome was only the first step in our quest to understand how genes are expressed and regulated. Sitting above the DNA sequence is a second layer of information (the ‘epigenome’) that regulates several genomic functions, including when and where genes are turned-on or -off. ‘Epigenetics’ refers to the reversible regulation of gene expression mediated principally through changes in DNA methylation and chromatin structure. Epigenetic processes are essential for normal cellular development and differentiation, and allow the regulation of gene function through non-mutagenic mechanisms. Unlike the DNA sequence, which is stable and strongly conserved, epigenetic processes are tissue-specific, developmentally-regulated and relatively dynamic. For example, mounting evidence suggests that epigenetic processes can be influenced by exposure to a range of external environmental factors, either globally or at specific loci.
The SGDP Psychiatric Epigenetics Group was established in 2007 and utilizes the cutting-edge facilities at the SGDP to explore the role of epigenetic processes in behaviour and susceptibility to neuropsychiatric disease. Current studies focus on:
1) genomewide investigations of DNA methylation in post-mortem brain tissue for disorders such as schizophrenia, bipolar disorder, autism and Alzheimer’s disorder
2) investigating the role of epigenetic variation in mediating phenotypic variation between genetically-identical individuals (i.e. monozygotic twins, inbred animals)
3) elucidating how external environmental factors may bring about long-term changes in gene expression via epigenetic alterations
4) identifying novel imprinted regions of the genome, and their role in mediating parent-of-origin effects in psychiatric disorders
5) exploring interactions between the epigenome and inherited DNA sequence variation actin in cis.
6) uncovering the mechanism behind the association between advanced paternal age and risk for neuropsychiatric disorders
Epigenetic dysfunction can explain numerous epidemiological, clinical, and molecular peculiarities associated with psychiatric disorders that are difficult to rectify using traditional gene- and environment-based approaches. These include the incomplete concordance between MZ twins, a fluctuating disease course with periods of remission and relapse, sexual dimorphism, peaks of susceptibility to disease coinciding with major hormonal rearrangements, and parent-of-origin effects. Our lab aims to explore the role of epigenetic factors in mediating susceptibility to a number of psychiatric conditions including schizophrenia, bipolar disorder, major depression, attention-deficit hyperactivity disorder, and autism.
Jonathan Mill (Senior Lecturer in Psychiatric Epigenetics)
Emma Dempster (Postdoc)
Manuela Volta (Postdoc)
Chloe Wong (MRC PhD student) -- Project: Epigenetic Differences in Twins
Ruth Pidsley (MRC PhD student) -- Project: Profiling DNA Methylation in Post-Mortem Brain Tissue
Rebecca Smith (PhD student) -- Project: Paternal Age as a Risk Factor for Autism and Schizophrenia
Rachel Kember (PhD student - primary supervisor Dr Leo Schalkwyk) - Project: Epigenetic changes in response to maternal separation in rodents
National Institutes of Health (NIA and NIMH) Epigenomics Roadmap Initiative
NIHR Biomedical Research Centre
The Royal Society
London University Central Research Fund
British Medical Association
Alzheimer’s Research Trust