Around two thirds of adults do not respond to the first trial of antidepressants meaning depression often goes untreated leading to severe complications. This may be due to antidepressants targeting the wrong mechanisms underlying depression, meaning alternative anti-depressive pathways must be targeted. Alternative routes include inflammatory pathways which have been associated with the development and pathogenesis of depression, demonstrated in a prospective study linking cytokine Interleukin 6 (IL-6) in childhood to depression later in life. The ways in which IL-6 contribute to depression remain unclear, and this study aims to investigate this relationship.
This study will investigate the role of cognitive biases, specifically negative biases, in the association between inflammation and depression. Cognitive biases are systematic deviations from normality when processing information; negativity bias refers to a negative shift in emotional processing. The neurocognitive model of depression suggests that negative biases have an important role in the development and maintenance of depressed mood. While there is a significant amount of research mapping neurotransmitter pathways of these cognitive mechanisms, the role of inflammatory pathways is largely unknown. This study aims to bridge this knowledge gap investigating the causal relationship between IL-6 serum levels with emotional processing, specifically negativity bias. This may highlight a new neurocognitive pathway between inflammation and depression, suggesting that IL-6 levels may cause changes in emotional processing subsequently maintaining depressed mood.
There is a small amount of research already suggesting an association, however there are significant experimental issues meaning a causal relationship cannot be drawn. Most research uses small samples of specific populations e.g. breast cancer patients in cross sectional designs. The extant research is at risk of inflated effect sizes due to moderation of chronic inflammatory disease, meaning the relationship between inflammation and negativity bias may be larger than in healthy populations. Additionally, there is a risk of depression mediating this relationship. Current research lacks a large sample prospective study, adjusted for moderation of chronic inflammatory illness, mediating effect of depression and several confounding variables.
This study will use ALSPAC data to investigate the relationship between IL-6 serum levels in childhood through to early adulthood and negativity bias in early adulthood. Using a large longitudinal data set allows for a temporal, directional relationship to be determined. Adjusting for confounders, testing for moderation of disease and mediation of depression means a valid, causal association can be investigated between IL-6 and negativity bias.