Are genetic markers helpful in understanding psychological disorders?

The debate Marked for Life: Are Genetic Markers Helpful in Understanding Psychological Disorders?, organised jointly by the Progress Educational Trust (PET) and the Royal Society of Medicine (RSM), took place in the RSM's main lecture theatre on the evening of 3 March 2010. The event formed part of the broader PET project 'Spectrum of Opinion: Genes Autism and Psychological Spectrum Disorders', which is supported by the Wellcome Trust.

Over 200 people attended the debate, including a party of students and teachers from Robert Napier School in Gillingham who will pilot a 'Spectrum of Opinion' resource pack developed by PET later in 2010. The debate was chaired by Dr Anand Saggar, President of the RSM's Medical Genetics Section and also Senior Consultant in Clinical Genetics at St George's NHS Trust.

The focus of the discussion was the five neurodevelopmental disorders (autism, attention-deficit hyperactivity disorder, bipolar disorder, major depressive disorder and schizophrenia) currently being studied by the Psychiatric Genome-Wide Association Study Consortium (PGC) in what is said to be the 'largest biological experiment ever conducted in psychiatry' (1).

The first speaker was Nick Craddock, Professor of Psychiatry and Honorary Consultant Psychiatrist at Cardiff University, who leads the Bipolar Disorder Component of the Wellcome Trust Case Control Consortium and is also one of the Coordinators of the PGC. He began by observing that our understanding of what causes mental illness is relatively poor, and that diagnoses of mental illness are generally not made using laboratory tests, but instead by observing complex clinical features. How can we improve upon current diagnoses and treatments?

With many psychiatric disorders, there is a clear correlation between the risk of developing the disorder and the existence of the disorder in other members of a family. Furthermore, the increase in risk when the family member with the disorder is an identical twin leaves little doubt that there is a genetic mechanism behind the heritability of these conditions. That said, because developing a psychiatric disorder that already exists in a family remains a risk rather than a certainty, genetics alone cannot account for psychiatric illness. Professor Craddock further argued - and insisted, when pressed on the point by Dr Saggar - that there is no possibility of discovering a 'gene for' any of the neurodevelopmental disorders being studied by the PGC. By a 'gene for', he meant a genetic marker that straightforwardly accounts for the disorder's presence or absence.

The second speaker was Derek Bolton, Professor of Philosophy and Psychopathology at the Institute of Psychiatry at King's College, London. He too discussed the challenges presented by the complexity of the genetics underlying psychiatric illness and by the fact that we have so far tended only to discover combinations of genes responsible for small effects. Although other fields of scientific endeavour have been characterised by increasing clarity, as they become better able to distinguish the essential from the peripheral, Professor Bolton feared that the genetics of mental health may be an area where 'nature does not oblige' - in other words, where complexity is endemic and intractable.

Professor Bolton then discussed the promise of new treatments emerging from genetic research into mental health - for example, the idea of psychopharmacogenetics, where medications might be developed that target individuals with a particular genetic profile. He also discussed environmental intervention, where changes of lifestyle and circumstance might be prescribed to mitigate psychiatric illness. He concluded his initial remarks by asking whether current research can improve genetic and environmental profiling options, so those at risk of psychiatric illness can be better identified and helped at an earlier stage.

The third speaker was Fenno Outen, Head Occupational Therapist for Newham at East London NHS Foundation Trust. He began by asking how the genetics of mental health relates to the prevailing culture (preferring the category 'culture' to describe human affairs over the broader category 'environment'). He said mental health services tend to consider themselves 'Cinderella services', which could help people more effectively if only they were better resourced. At the same time, he cited studies appearing to show there is surprisingly little difference in outcome between those with mental health problems in the developed and in the developing world, given the disparity in wealth.

Mr Outen discussed the term 'biopsychosocial', sometimes used to account for the diverse possible causes of psychiatric illness. He argued that it is 'cheeky' to describe this concept as a 'model', as some are wont to do, because it is not sufficiently coherent - other models in science and medicine distil meaning from the world, whereas biopsychosocial theories leave us none the wiser. Mr Outen's principal concern about the cultural dimension of mental health was its vulnerability to deterministic ideas about human wellbeing. This means concepts such as 'work-related stress' can be created through culture, but later become a 'uniform force' that impacts adversely upon people's mental health.

The discussion following these introductory speeches began with Larry Arnold, an academic and disability rights campaigner who himself has a diagnosis of Asperger's syndrome. He questioned the nosology (classification of disease) that underpins current research into the biology of mental health. This theme arose in several questions and comments from the audience, and Professor Craddock conceded that existing diagnostic categories may not map precisely onto the biological mechanisms that are found to underpin mental health problems. Nonetheless, Professor Craddock argued that these diagnostic categories are as good a place as any to start from.

PET's Chair of Trustees, Professor Marcus Pembrey, asked whether we are overlooking the possible role of 'protective genes' in mental health - that is, particular genetic markersthat prevent mental illness manifesting in individuals who are otherwise genetically and environmentally predisposed to develop it. Such individuals do not exhibit the mere absence of disease, but rather possess a distinct genetic trait that it would be useful to identify and understand. The panel agreed that this is a possibility, but Professor Craddock was concerned about the practicalities of designing an experiment that could test this hypothesis.

Asked whether the term 'environment' is inadequate for capturing the dynamics of human society, and whether Mr Outen's category of 'culture' is preferable, Professor Bolton said the term 'environment', as currently used, is 'extremely broad' and tends to simply mean 'not genetic'. He said 'gene/environment interaction' is a 'statistical notion' (notwithstanding that the growing field of epigenetics may establish a biochemical basis for it). Also that our understanding of 'environmental risk' does not come from genetic research, but rather from longtitudinal studies of at-risk cohorts and from health economists and social scientists examining large-scale populations. He listed some of the social, economic and political factors that could be said to constitute environmental risk factors, prompting Dr Saggar to say: 'Short of standing for Parliament, I don't see how you could do much about any of those'.

In their concluding remarks, all three speakers said the answer to the question implicit in the event's title - if you are genetically predisposed to a neurodevelopmental disorder, does this effectively mean you are marked for life? - is an emphatic 'no'. Nonetheless, the speakers had divergent views on the likelihood of successfully applying the fruits of genetic research into mental health. Professor Bolton was somewhat pessimistic about future prospects, Professor Craddock more optimistic, and Mr Outen said further research is needed before it is possible to say one way or the other.