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 Slater's 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 (Reference Folstein and Rutter1977), suggesting for the first time that childhood autism, far from reflecting the influences of ‘refrigerator parents’, is substantially genetic.

Michael Rutter's 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.

Developmental theme

The Centre's 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 Centre's 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 Centre's 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 Centre's 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 (Reference Plomin, Owen and McGuffinPlomin 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 Centre's plan.

1. (a) We believe that progress in identifying genes associated with common behavioural disorders has been slower than many had predicted because studies have been inappropriately designed and underpowered for finding QTLs of small effect size. A common approach of the Centre's current genetic studies is, therefore, to collect very large samples, establish them as resources and develop designs and methods that are capable of detecting and replicating QTLs of small effect size.

2. (b) High-throughput technologies have been adopted and developed. These allow both linkage and linkage disequilibrium mapping and a focus on direct association analyses using functional DNA variants expressed in the brain, including sets of variants that can be used to explore entire neurotransmitter pathways.

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 (Reference McGuffin, Riley and PlominMcGuffin et al, 2001; Reference Plomin, DeFries and CraigPlomin 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 (Reference Peltonen and McKusickPeltonen & 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 (Reference McGuffin, Riley and PlominMcGuffin 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 (Reference Plomin, DeFries and McClearnPlomin 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, Reference Caspi, McClay and Moffitt2002, Reference Caspi, Sugden and Moffitt2003). 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.