Abstract
In influencing risk for psychiatric and substance use disorders, genes are typically conceptualized as working in silent physiological pathways in the bowels of our biology, far from the influences of human desires. I here argue that this model of gene action is too restricted. At the individual, family and societal level, humans can, through their decision-making capacity, intervene in causal pathways from genes to behavior. At the individual level, I present four paradigmatic cases involving alcohol dependence, major depression, general externalizing behaviors and animal phobia showing how human decisions can inhibit the expression of risk genes. I review the literatures demonstrating that parental behaviors can suppress or augment the heritability of traits in their children, and social attitudes can alter and even create causal pathways from genes to phenotypes. We evolved from organisms whose nervous systems were networks of reflexes that then developed simple cognitive systems and finally self-reflection. Just as our cognitions have gone ‘meta,’ we are now nearing a time when we can go ‘meta’ about our genetic risk. For many psychiatric disorders, our risk genes are not entirely cordoned off in our silent, purposeless biological substrate. Rather, we are able to make decisions that impact on the expression of our own genomes, those of our loved ones and those of our friends and neighbors. Our actions and our genes are often weaved together, integrated into the fabric of our lives.
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Acknowledgements
Supported in part by NIH Grants AA011408 and DA030005. Several key ideas expressed here arose during discussions with John Campbell, PhD, Peter Zachar, PhD, and Richard Bonnie, LLB, and provided helpful comments on earlier versions of this essay. Jennifer Kendler assisted in writing the story of James. This paper was based on the 14th P. Browning Hoffman Memorial Lecture delivered at the University of Virginia's School of Law on September 7, 2011.
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Kendler, K. Decision making in the pathway from genes to psychiatric and substance use disorders. Mol Psychiatry 18, 640–645 (2013). https://doi.org/10.1038/mp.2012.151
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DOI: https://doi.org/10.1038/mp.2012.151
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