Inflammation does not mediate an adverse childhood experience– self-harm risk association

Last updated 4 January 2024

Inflammation has been proposed to be a candidate mechanism contributing to the association between exposure to adverse childhood experiences (ACEs) and the risk of self-harm.1-2 In the first study of its kind, researchers in the UK have now directly studied whether inflammatory processes do indeed mediate this association. Abigail Russell and colleagues used data from >4,000 adolescents recruited to the UK population-based birth cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC).3

They modelled the number of ACEs experienced between ages 0 and 9 years, the levels of interleukin-6 (IL-6) and c-reactive protein (CRP) (key markers of inflammation) at age 9.5 years and the number of self-harm reports at age 16 years. They confirmed that ACEs between 0-9 years were associated with an increased risk of adolescent self-harm. Furthermore, each additional ACE conferred an additional 11% risk of self-harm at 16 years-of-age. They found no evidence, however, to support that their measures of inflammation mediated this ACE–self-harm association in their sample.

The researchers propose many reasons for their result. For example, they suggest that inflammation might impact on self-harm via an altered inflammatory response to immune system challenges. Alternatively, previous studies might have detected inflammatory consequences of self-harm, rather than have detected inflammation as an antecedent to self-harm. Based on their data thus far, however, the researchers do not consider that inflammatory markers are a useful biomarker of self-harm risk in those exposed to ACEs.

Russell, A. et al. (2019), Pathways between early life adversity and adolescent self-harm: the mediating role of inflammation in the Avon Longitudinal Study of Parents and Children (ALSPAC). J. Child Psychol. Psychiatr. doi:10.1111/jcpp.13100


1Baumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M. and Mondelli, V. (2016). Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol. Psychiatry, 21: 642-649. doi: 10.1038/mp.2015.67.

 2Coelho, R., Viola, T., Walss-Bass, C., Brietzke, E. and Grassi-Oliveira, R. (2014). Childhood maltreatment and inflammatory markers: a systematic review. Acta Psychiatr. Scand., 129: 180-192. doi: 10.1111/acps.12217. 

 3Boyd, A., Golding, J., Macleod, J., Lawlor, D. A., Fraser, A., Henderson, J., et al. (2013). Cohort profile: the ‘children of the 90s’—the index offspring of the Avon Longitudinal Study of Parents and Children. Int. J. Epidemiol., 42: 111-127. doi: 10.1093/ije/dys064.

This paper forms part of the JCPP Special issue 2019 – Suicide and self-harm: Pathways for Minimizing Suicide & Premature Deaths and Maximizing Hope and Wellbeing.

Watch Dr. Abigail Russell discuss this paper in this short video.