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Event Review: The Genetics of Mental Health – Episode one

12 October 2020
Appeared in BioNews 1067

We get a great deal of mileage out of the terms 'nature' and 'nurture', even though thinking about evolution, human beings, and life using these supposedly distinct and mutually exclusive labels is surely a gross simplification. I have a few theories as to why: the pairing – 'nature vs nurture' – confers an agreeable, comedy-duo aesthetic; 'nature' is innate, and therefore beyond our control, whilst 'nurture' is environmental, and thus also not our responsibility.

Trying to define mental health, with its cryptic definitions and antiquated social stigmatisation, in terms of its biological and environmental causes presents a unique problem. However, Professor Cathryn Lewis, head of King's College London's Social, Genetic, and Developmental Psychiatry Centre and the event's first speaker, points out that mental health, and associated disorders, have long been known to have a strong hereditary component, by virtue of family history. But how do we reconcile the inherent ambiguity and complexity of mental disorders with the assumed certainty and determinism of genetics and, more importantly, how can this translate into a more intelligent approach to diagnosing and treating mental disorders?

This webinar, organised by the Royal Society of Medicine (RSM) and the first in its The genetics of... series, not only presented a clear and concise overview of the work which has been undertaken in this field, but also demonstrated how we can talk about a sensitive and complicated topic constructively and comprehensibly. The three talks, presented by Professor Lewis, Professor Andrew McIntosh, the chair of biological psychiatry at the University of Edinburgh, and Dr Kimberley Kendall, a Wellcome clinical research fellow, differed enough to display the breadth of research being undertaken, whilst also overlapping sufficiently to demonstrate where this research intersects, and how these links facilitate our increased knowledge of mental health's underlying roots.

The first aspect of the webinar, which I was particularly impressed by, (other than the fact that thanks to the RSM and moderator Dr Melita Irving, the event ran smoothly and without a single technical mishap) was the approach taken by the speakers to explaining terminology and methodology. This became clear when Professor McIntosh, whose talk focused on coupling initial genetic studies of depression with environmental risk factors and mechanisms behind mental disorders, described Mendelian Randomisation, a technique used to harness the, as he put it, 'causal anchor' of genetics to identify causal relationships. This extended to all three talks, where the formation of polygenic risk scores, large array copy number variants, the consolidation of genetic studies with neuroimaging, and the intricacies of the UK Biobank are detailed succinctly, though without excessive simplification. This revelling in the field's ingenuity and complexity was reassuring, and it set a precedent for the webinar as a whole.

I also appreciated how the speakers continuously drew attention to the pitfalls and limitations of current work. One example is the underrepresentation of non-European ethnicities in large genetic studies, resulting in loss of applicability to a diverse population, and therefore a decrease in potential clinical relevance and understanding. Additionally, there are the difficulties in establishing strong boundaries for, and definitions of, mental disorders as shown clearly by Dr Kendall through the 'neurodevelopmental spectrum'. Professor McIntosh also mentions that psychiatry suffers during diagnosis due to a focus on symptoms to define illness, whereas it would be more useful to apply aetiologies as soon as they are established, which was an interesting perspective I had not heard before.

What this culminated in was an informative, fascinating event which stated explicitly what genetics can explain about mental disorders, as well as what it might explain in the future, and what it may never explain. This was perhaps articulated best by Dr Kendall during the panel discussion, who said 'In psychiatry, you do not inherit disorders, you inherit a risk of a disorder'. It is understandable why this may be frustrating and, indeed, many of the questions asked during the discussion involved biological pathways, clinical relevance, and unexplained variability. Professor Lewis clarifies that 'once we are in polygenic territory then all of these [single nucleotide polymorphisms (SNPs)] have very modest effects', and this summarises the attitude which the speakers were likely encouraging the audience to embrace: there will never be a 'depression gene', but that doesn't mean that genetics still cannot tell some of the story, even if it leaves parts open-ended.

The debates, inside and outside academia, surrounding the role of genetics and the extent of its determinism have become loaded with politics and emotion: from the admiringly professional, if not heated, Harden vs Plomin rivalry, to Dominic Cummings having a crack at whatever it is he cracks at. Admittedly (having done limited research into the speakers prior to the event), I was half-anticipating, and maybe even half-hoping for, an hour of impassioned furore, pointed fingers, and the occasional personal remark. Maybe it is because we are still obsessed with binary classification of 'nature' and 'nurture', and struggle to accept the irremovable complexities at the heart of psychiatry. However, this webinar is as good an argument as you will get for shaking off old assumptions and approaching genetics and mental health with a fresh perspective.

SOURCES & REFERENCES
The genetics of mental health: Episode 1
The Royal Society of Medicine |  28 September 2020
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