Shifting the focus from just ‘vulnerability.’ In this blog, Alicia Peel explores differential susceptibility and how it develops our understanding of the gene-environment interaction.

Alicia Peel, EDIT Lab PhD student






Why is it that not all people who experience the same event will react in the same way?

This question has formed the basis of research into gene-environment interaction, the mechanism through which genetic predispositions influence how we experience the world and, in turn, how the environment influences the expression of our genes. Genetic and environmental influences are described as interacting, as neither one on their own may cause an outcome, but the combination of the two factors together influences a specific response.

Gene-environment interaction is an important concept in psychological research, as it may help us to understand why some people develop a disorder after a stressful or traumatic experience, while others do not.  For example, those who have particularly high genetic risk for depression may be more likely to develop symptoms after experiencing a stressful event, whereas others who experience the same event but have low genetic predisposition may develop more mild, or no, symptoms. This research shows that genetic factors may influence the risk of disorder onset, in part by altering a person’s susceptibility to adverse environments. 


But what about positive experiences?

Although there is often a focus on adverse environments when thinking about mental health, there are also many positive experiences that play an important role in an individual’s outcomes. These could include having a supportive network of family or friends, or experiencing situations designed to promote mental wellbeing, such as psychological therapy. These experiences may also interact with pre-existing genetic factors to influence positive outcomes. For example, having higher genetic liability for the personality trait openness is associated with a greater response to antidepressant medication.

When considering both adverse and positive environments, our understanding of gene-environment interaction can shift from focusing only on “vulnerability” to negative experiences towards broader “sensitivity” to the environment as a whole. Sensitivity to both negative and positive aspects of the environment is termed differential susceptibility, and is illustrated in the figure below. Under this framework, individuals who are generally less sensitive to their environments, the red line, have comparable moderate outcomes across both adverse and supportive environments. Those who are generally more sensitive to their environments, the purple line, are more susceptible to both negative outcomes in adverse environments but also to positive outcomes in supportive environments.


Does this mean that being highly sensitive is bad?

Not at all! The development of differential susceptibility theory reflects a broader change of perspective in psychiatry, moving away from a focus on risk and vulnerability and towards an understanding of resilience and embracing of individual differences. In line with this theory, both high and low sensitivity are viewed as valuable characteristics. While those with a lower genetic predisposition to sensitivity may be more resilient when faced with challenges, those with a higher genetic loading for sensitivity may be more responsive to positive changes in their environment. 



Peyrot, W. J., Milaneschi, Y., Abdellaoui, A., Sullivan, P. F., Hottenga, J. J., Boomsma, D. I., & Penninx, B. W. J. H. (2014). Effect of polygenic risk scores on depression in childhood trauma. The British Journal of Psychiatry, 205(2), 113–119.

Thapar, A., Harold, G., Rice, F., Langley, K., & O’Donovan, M. (2007). The contribution of gene–environment interaction to psychopathology. Development and Psychopathology, 19(4), 989-1004.

Belsky, J., Jonassaint, C., Pluess, M., Stanton, M., Brummett, B., & Williams, R. (2009). Vulnerability genes or plasticity genes?. Molecular Psychiatry, 14(8), 746-754.

Pluess, M., Lionetti, F., Aron, E. N., & Aron, A. (2020). People Differ in their Sensitivity to the Environment: An Integrated Theory and Empirical Evidence. PsyArXiv. doi:10.31234/

Alicia Peel

Author Alicia Peel

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