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The Genetic Epidemiology of Psychiatric and Substance Abuse Disorders: Multiple Levels, Interactions and Causal Loops

What causes psychiatric disorders, such as depression or alcohol abuse disorders? It’s obvious that  background and upbringing often play a significant role, as do life events, such as losing one’s spouse or one’s job. And we also know now that genetic propensities are  important. But how do these different factors inter-relate with one another? For over three decades, these issues have been at the centre of the research of Oxford’s first Loebel Lecturer, Professor Kenneth Kendler.

Professor Kendler is one of the world’s leading, and most highly cited, psychiatric researchers. He uses a range of methods, including family studies, twin and adoption studies, and molecular genetics. He also has a serious interest in the philosophy of psychiatry. His first Loebel Lecture — The Genetic Epidemiology of Psychiatric and Substance Abuse Disorders: Multiple Levels, Interactions and Causal Loops – was presented at the Oxford Martin School on Wednesday 15 October 2014, and is now available on Youtube and as an MP3 audio file.

This lecture lays out the empirical background to the second lecture, in which Professor Kendler goes more deeply into the philosophical issues raised by his findings. The lecture shows – elegantly, rigorously, and clearly – the complexity of the causal stories behind individual episodes of psychiatric and substance use disorders. Consider gene-environment interactions in major depression. Twin studies show that, if your twin has major depression, you have a latent genetic risk of developing depression yourself, but are also more sensitive to the depressogenic effects of stressful life events.

There is also gene-social interaction in, for example, drug use. Here Kendler demonstrates how, if you have a greater-than-average genetic propensity to drug abuse and find yourself in an environment generally supportive of such abuse (e.g. in a drug-abusing family), you will be many times more likely to abuse drugs than someone without that propensity.

There can also be interaction between different environmental risk factors. Kendler’s key example here is that of women abused in early childhood who then face stressful life events. Again, the level of interaction is clear and demonstrable.

Kendler also demonstrates correlations between genotype and environment. One can find significant heritable components in, for example, the quality of marriage or the deviance of peer groups in adolescence. Genes affect our own lives directly, but they also ‘loop out’ into the environment. Consider someone prone to alcohol abuse. That genetic propensity will make them more likely to find a peer group supportive of such abuse. And without such a group, they might be just fine.

Kendler goes on to bring out the place of  genetic factors in explaining the comorbidity of psychiatric disorders, and concludes with two fascinating and moving individual cases which he suggests demonstrate ‘top-down’ causation in which a human decision affects whether one’s genes will or will not express themselves in psychiatric or substance use disorders.

The lecture is followed by a lively question-and-answer session, in which Kendler deals with issues such as whether his alleged cases of top-down causation can be explained reductively, the implications of uncertainties in modelling for public mental health, and the relation of his results to DSM.

Though Kendler himself is disarmingly modest, his results seem to me to have hugely significant implications for the treatment of – and perhaps even more importantly the prevention of – various disorders. And perhaps even he would admit that he has played a major role in changing psychiatry itself from a discipline in which it was acceptable to say ‘In my clinical opinion…’ to one that relies ever more on hard data.

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