Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK
Correspondence: Professor Peter McGuffin, Social, Genetic and Developmental Psychiatry Centre, PO Box 80, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. E-mail: p.mcguffin{at}iop.kcl.ac.uk
DECLARATION OF INTEREST P. McG. and R. P. are Director and Deputy Director, respectively, of the centre described in this paper.
* This is the first of a short series of editorials being published in the
Journal to mark the 10th anniversary of the Social, Genetic and
Developmental Psychiatry Centre at the Institute of Psychiatry.
October 2004 sees the tenth anniversary of the founding of the Social, Genetic and Developmental Psychiatry Centre, established as a partnership between the Medical Research Council (MRC) and the Institute of Psychiatry (now a school of Kings College London). This editorial gives an account of how the Centre came to be founded and an introduction to its work, as the first in an invited series of short articles describing the Centres research. A more detailed account is given by Rutter & McGuffin (2004).
Social, genetic and developmental research at the Institute of Psychiatry
Social, genetic and developmental streams of research have all existed at
the Institute of Psychiatry since its establishment in 1948, but they were not
always integrated and indeed there have been times when genetic researchers
and social psychiatrists were in a state of open, mutual hostility. Such
intellectual warfare reached its height in the 1960s and 1970s when social
psychiatry was in the ascendancy, with its practitioners seeing themselves as
occupying the moral high ground in the nature v.
nurture debate. Certainly, things had started off on a better footing
at the Institute. Aubrey Lewis, who was appointed in 1948 as the director of
the first MRC unit at the Institute of Psychiatry (the Social Psychiatry
Research Unit), saw social psychiatry as a broad field that
included consideration of the biological substrate of disorders as well as
social causes. Indeed, it was he who in the 1930s had encouraged Eliot Slater
to study genetics. Slater, now considered the founding father of
psychiatric genetics in the UK, established another MRC unit at the Institute
of Psychiatry in 1959 the Psychiatric Genetics Unit. This unit, which
was housed in a prefabricated building known as the hut, was
closed on Slaters retirement in 1969, and for the next decade
psychiatric genetics largely fell out of fashion in the UK. There were,
however, a few notable exceptions to this neglect, one of which was a seminal
twin study by Folstein & Rutter
(1977), suggesting for the
first time that childhood autism, far from reflecting the influences of
refrigerator parents, is substantially genetic.
Michael Rutters early research path had been established in the MRC Social Psychiatry Research Unit led by Lewis, and he continued, as his career matured, to take an integrated approach. This was a strong feature of the Institute of Psychiatry Child Psychiatry Department under his leadership and continued with the establishment of the MRC Child Psychiatry Unit in 1984. The unit brought together experts in a variety of overlapping fields: early social development, longitudinal studies of the general population and high-risk samples, genetics and statistical methods. The mix proved highly successful, and over the first 10 years of its existence the Child Psychiatry Unit had a major impact on child psychiatric research nationally and throughout the world. Meanwhile, it was the turn of social psychiatry to become unfashionable, at least in the sense of a discipline that was narrowly focused on social influences without much heed for biological or developmental dimensions. In 1993 the MRC took the decision to close the Social and Community Psychiatry Unit (as it had then been named). However, it did not seem either to the MRC or to the Institute a correct decision to abandon social psychiatry entirely after more than 45 years of influential research. Rather, there was a need for refocusing, and reintegration with other strands of research that were proving fruitful elsewhere in psychiatry. One of these was the now rejuvenated discipline of psychiatric genetics, and the other lay in the proposition that disorders of adult life not just childhood disorders might be profitably seen as neurodevelopmental.
ESTABLISHMENT OF THE CENTRE
Michael Rutter and David Goldberg, then head of the Institutes Department of Psychiatry, opened discussions with the MRC about establishing an interdisciplinary research centre that could, in a comprehensive way, study the interplay of nature and nurture in the development of common psychiatric symptoms and disorders. This led to a successful application for an MRC programme grant to provide core infrastructure support for a centre that under Rutters directorship could harness existing Institute expertise and draw in top-flight recruits from around the world to achieve this ambitious scientific goal. Robert Plomin, a behavioural geneticist at Pennsylvania State University, was appointed as deputy director, and other prestigious appointments soon followed (Table 1).
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From the beginning, the Centre was a partnership between the Institute and the MRC, and was successful in obtaining grant funding from a variety of other sources including medical research charities, the US National Institutes of Health, and industry. By the time of Michael Rutters retirement as director in the autumn of 1998, the Centre had grown to comprise around 90 scientific, technical and administrative staff spread over eight different buildings on the Maudsley/Institute campus. Peter McGuffin, an adult psychiatrist with a longstanding interest in genetics and geneenvironment interplay, was appointed as the new director. As the incoming director, he had two major tasks: the first was to secure renewal of the Centres core funding from the MRC, and the second was to find funding for a building that would accommodate all of the Centres research groups under one roof. This entailed an application to the UK government and the Wellcome Trusts newly established joint infrastructure fund. Fortunately, both applications were successful and a new round of recruiting could begin. The final element in the configuration of the Centre resulted from integration of the MRC Child Psychiatry Unit under the leadership of Professor Eric Taylor.
OVERALL STRATEGY AND WORK OF THE CENTRE
The Centres current focus is on common psychiatric disorders, covering three domains: mood disorders (especially anxiety and depression), externalising disorders (especially disruptive behaviour including hyperactivity) and cognitive disorders (especially language disorders and mild learning disability, including autistic symptoms). The Centre concentrates on the aetiological aspects developmental as well as genetic and environmental origins of behavioural disorders. However, there is a strong emphasis on methods of measurement and classification and an attempt to foresee the practical, clinical and public health implications of the Centres findings.
Developmental theme
The Centres developmental theme leads to research focused on
childhood disorders, because relatively little is known about them despite
their public health importance. However, a developmental perspective involves
more than studying children it is an aetiological approach that
investigates when and how disorders emerge and change during development and
how these aspects of course are influenced by genetic inheritance and social
environment. This focus on change and continuity in development is the reason
why much of the Centres research is longitudinal. We believe that such
research is essential to the development of interventions that prevent the
onset of disorders, rather than waiting to treat full-blown disorders. In
addition, the Centres approach to development spans the life course: of
considerable current interest are adult outcomes of childhood disorders such
as hyperactivity and language disorders, and similarities and differences in
the forms of depression that emerge in childhood, adolescence, and early and
late adulthood, respectively.
Genetics theme
The Centres strategy has been to build strength in quantitative
genetics as well as in molecular genetics, because both are vital to the
understanding of complex traits. Quantitative genetic approaches, such as twin
studies, are central to our themes and, properly applied, can tell us as much
about the environment as about genetics. Quantitative genetics, which
considers complex quantitative traits influenced by multiple genes as well as
multiple environmental factors, also provides the foundation for quantitative
trait locus (QTL) strategies for molecular genetics
(Plomin et al, 1994).
The QTL perspective pervades molecular genetic research in the Centre, because
much of the liability to common disorders is likely to be on a continuum of
variation. Therefore, risk factors for common disorders probably represent the
quantitative extreme of the same genetic and environmental factors that create
variation in the normal range. In terms of molecular genetics, two strategic
directions are part of the Centres plan.
Such gene-finding approaches, although intensive and time-consuming, are only a prelude to functional genomics that will involve developments in bioinformatics and the integration of genomics, gene expression, proteomic and brain research relevant to behavioural analysis. Together with top-down whole-organism studies, these approaches constitute what might be called behavioural genomics (McGuffin et al, 2001; Plomin et al, 2003).
Environmental theme
Research on the environment is in many ways more difficult than research on
genetics. Genetics is entering a golden post-genomic era
(Peltonen & McKusick, 2001)
in which the structure and function of the entire genome will eventually be
known. In contrast, there is no environome project. Indeed,
there are no laws of environmental transmission and there is nothing like a
simple triplet code. Another important factor in the slow progress towards
understanding the environment has been the traditional tendency of social
psychiatry to ignore genetics or to consider environmental influence as in
opposition to genetics. In fact, two of the most important sets of discoveries
about environmental mechanisms in the past decade have come from genetic
research, including work by Centre members. The first finding is that,
contrary to most socialisation theories, environmental influences on many
traits tend to be of the non-shared type
(McGuffin et al,
2001): that is, they tend to make children growing up in the same
family as different as children growing up in different families. A priority
for environmental research therefore should be to identify these environmental
factors. The second finding, sometimes called the nature of
nurture, is that genetic factors influence the way we experience our
environments (Plomin et al,
2001). Thus, some measures ostensibly of environmental risk
such as life events and psychosocial stress show genetic
influence. Similarly, associations between environmental risks and disorders
are often substantially mediated genetically (Caspi et al,
2002,
2003). Our view of the way
forward is to bring together genetic and environmental strategies using
environmental measures within genetic designs to investigate co-actions,
interactions and correlations between environmental risks and genetic
susceptibilities.
REFERENCES
Caspi, A., McClay, J., Moffitt, T. E., et al
(2002) Role of genotype in the cycle of violence in
maltreated children. Science,
297, 851
-854.
Caspi, A., Sugden, K., Moffitt, T. E., et al
(2003) Influence of life stress on depression: moderation by
a polymorphism in the 5-HTT gene. Science,
301, 386
-389.
Folstein, S. & Rutter, M. (1977) Genetic influences and infantile autism. Nature, 265, 726 -728.[Medline]
McGuffin, P., Riley, B. & Plomin, R. (2001)
Genomics and behavior: toward behavioral genomics.
Science, 291, 1232
-1233.
Peltonen, L. & McKusick, V. A. (2001)
Genomics and medicine. Dissecting human disease in the postgenomic era.
Science, 291, 1224
-1229.
Plomin, R., Owen, M. J. & McGuffin, P. (1994) The genetic basis of complex human behaviours. Science, 264, 1733 -1739.[Medline]
Plomin, R., DeFries, J. C., McClearn, G. E., et al (2001) Behavioral Genetics (4th edn). New York: Worth.
Plomin, R., DeFries, J. C., Craig, I.W., et al (2003) Behavioral Genetics in the Postgenomic Era. Washington, DC: APA Books.
Rutter, M. & McGuffin, P. (2004) The Social, Genetic and Developmental Psychiatry Centre: its origins, conception and initial accomplishments. Psychological Medicine, 34, 933 -947.[CrossRef]
Received for publication July 16, 2004. Revision received July 22, 2004. Accepted for publication July 22, 2004.