MRC Social, Genetic and Development Psychiatry Centre
Centre profile from the MRC Network publication issued Winter 2006/07.
The goal of the centre is to bridge the gap between "nature" (genetics) and "nurture" (environment) and discover how they interact in the development of complex behavioural dimensions and disorders.
Because the interaction between nature and nurture spans environmental approaches from epidemiology to family environment, and genetic approaches from twin and adoptee studies to molecular genetics, new collaborative interdisciplinary research is the hallmark of the centre.
The director, Professor Peter McGufin (left), lists the construction of the centre’s new home, which opened in 2003, as one of the pivotal moments in the centre’s history.
Early days
The centre grew out of the MRC Social Psychiatry Research Unit (SPRU). It was the brainchild of Sir Michael Rutter and Professor David Goldberg. By integrating genetic and psychiatric research, they aimed to show how the interplay between nature and nurture is involved in the development of psychiatric disorders. The centre is now home to 170 staff. It also plays host to numerous international visitors who are drawn by the promise of dynamic collaborations which are so essential to the work that goes on here: work that has led to greater understanding of mental health problems and diseases of the brain as well as the development of pioneering new treatments.
Early studies at the SPRU and the Child Psychiatry Unit clearly demonstrated the benefits of a more integrated approach to psychosocial research. In particular, pioneering work on twins suggested the need to focus on underlying genetic mechanisms. Although research in social psychiatry at the time was strong, the study of how social causes relate to various conditions was failing to keep pace and reliance on traditional methods was proving to be increasingly unsatisfactory. Making the connection between environmental influences and genetic factors was where the research at the SGDP Centre came into its own.
Finding a niche
Scientists at the SGDP Centre are involved in research spanning a number of disciplines: psychiatry, psychology, sociology, epidemiology, statistics and genetics. Incorporating a strong programme of genetics research into the centre’s portfolio pushed it ahead of the field. Peter McGufin says: “The trouble with genetics research now is that it’s so big that there was a danger of turning the centre into just another genetics laboratory. But what is unique about the SGDP Centre is that it goes beyond that and brings together all these perspectives, giving a much more coordinated approach to psychiatric disorders”.
The centre functions as both a department within the IoP and an overarching interdisciplinary research group. The first MRC centre of its kind, “this place was kind of like a prototype,” Peter explains. Integrating such a broad range of disciplines under one roof was seen as a pilot case to determine whether this sort of approach could work.
Peter first came to the centre in the 1980s, coinciding with the start of a new era in which molecular genetic research began in earnest. Having completed his training as a psychiatrist at the Maudsley Hospital in London, Peter was awarded an MRC fellowship to study genetics at London University and Washington University in St Louis, Missouri. This was followed by positions as an MRC Senior Clinical Fellow at the Maudsley and IoP, and chair of psychological medicine at the University of Wales in Cardiff.
In 1998, Peter returned to the SGDP Centre to succeed Sir Michael Rutter as director. He describes his position as “probably the best job in British psychiatry”. A professor of psychiatric genetics, he has worked extensively on the inherited basis of major mental illness but focuses particularly on the interplay between genes and the environment in mood disorders.
The centre has helped to pioneer a lot of the work in this area. Peter says: “Most people are still doing straight environmental studies or straight genetics studies, there aren’t many places that try to integrate the two. When I started as an MRC training fellow in the late 1970s it was very unfashionable to use genetics research in psychiatry.”
However, psychiatric genetics is fast becoming a major research area, attracting around 1,000 attendees to an annual meeting, now in its 14th year.
Leading senior scientists
During the 1990s, a number of other leading researchers in the field were appointed to the SGDP Centre. These included Professors Robert Plomin, Avshalom Capsi, Terrie Mofitt and Anne Farmer.
Peter McGufin, with his wife Anne Farmer, has masterminded a number of highly productive research collaborations. These include an ongoing study funded by the MRC and GlaxoSmithKline (GSK) to map genes that contribute to the cause of depression among affected siblings from eight different geographical sites around the world. “Although the details are quite complicated the basic idea is very simple”, says Peter. “You find someone who has depression who’s also got a sibling who is affected. Since siblings share half their genes, if you have siblings who are alike for a trait such as depression then you can run what’s called a genome scan as a way of mapping their entire genome”.
By identifying the genetic similarities between siblings, it may be possible to identify the genes that contribute to certain conditions. GSK’s interest lies in the potential to develop target-specific drugs, although they are also supportive of high-quality research, which Peter recognises as a particular strength in the collaboration. He says that the centre is interested in therapeutic drugs and has been involved in a big pharmacogenetics project over the last couple of years. Genetic testing would allow clinicians to predict how different patients are likely to respond to medication and whether they are likely to suffer side effects, according to how quickly their bodies break down a drug.
Large-scale longitudinal studies
Robert Plomin, Professor of Behavioural Genetics at the centre, is leading a particularly exciting research project on child development. His interests lie in harnessing the power of molecular genetics to identify genes for psychological traits. He heads the Twins Early Development Study (TEDS), which focuses on the early development of the three most common psychological problems in childhood: communication disorders, mild learning difficulties and behavioural problems. TEDS is the largest study of twins ever carried out in the UK – it is tracking 15,000 twins born in England and Wales between 1994 and 1996 for 15 years.
The study allows research teams to investigate the parts played by genes and the environment in common childhood disorders and other mental health problems. By regularly gathering information about the twins and sampling their DNA at various stages throughout their life, it’s easy to spot abnormal development. Peter McGufin explains: “We believe we can learn more about pathology by understanding more about the normal range.”
TEDS twins are assessed at two, three, four, seven and nine years old to investigate genetic and environmental contributions to language and cognitive development. The study also asks for input from parents and teachers, via face-to-face visits, telephone and online surveys, which help to give a clear indication of academic achievement as well as any behavioural problems.
DNA has been obtained from more than 5,000 twin pairs so far. Molecular genetic study of these twins has helped to identify specific genes involved in the development of conditions such as language impairment, hyperactivity, antisocial behaviour and autistic spectrum disorders. It has also helped to ind genes that determine reading, writing and mathematic ability.
Common childhood disorders
Research results from the SGDP Centre have shown that common childhood disorders such as language impairment have a strong genetic component. Children with autism spectrum disorders who normally start to show symptoms around the age of two or three find it hard to communicate with others. And such behaviours often occur throughout childhood and adolescence to varying degrees. This is why studying the TEDS twins is so useful in helping to understand how genes and the environment interact and how different sets of genes might influence the social and non-social features of autism. Recent research by the centre’s scientists has shown that autism is not a single psychological condition but a combination of two separate illnesses, controlled by different sets of genes. This finding has helped enormously in enabling proper diagnosis.
Mapping emotional intelligence in early years can also help to identify which children may be protected against or at risk of behavioural problems. This is useful in developing early intervention programmes and targeted educational approaches to help those children affected.
Research highlights
The success of the TEDS project has led to a number of spin-off studies. One of these is the E-risk (Environmental risk) project, headed by Professors Terrie Mofitt and Avshalom Caspi. The E-risk study involves studying a subgroup of TEDS twins to investigate how specific environmental risk factors contribute to the emergence of disruptive behaviour at a young age. Caspi and Mofitt, both senior researchers with an interest but no background in genetics, very quickly started to integrate genetic factors into their research. This, Peter McGufin says is “a good example of highly successful senior researchers coming into the centre with a background in environmental risk and applying not just twin methods but also molecular genetic methods, with great results.” The centre hopes that its long-term ‘behavioural genomics’ studies will improve understanding of how genes work at the behavioural level in relation to the developmental interplay between genetics and environment.
Multi-disciplinary collaborations are also very important to the centre and are central to its success. One exciting area currently in its early stages is the combination of genetics, genomics and imaging science. Collaborating with the newly built Centre for Neuroimaging Sciences at King’s College London has allowed brain scans to form part of the TEDS work, particularly in looking at how children’s brains process maths problems.
Clearly passionate about his research and the success of the SGDP Centre, Peter McGufin summarises the importance of the work there: “The more we understand, the less mysterious mental illness becomes and the less likely it is to be stigmatised.”