26. Polymorphisms in both immune and behavioural genes affect mood as part of the acute sickness response to infection

Abstract

The host response to infection triggers a distinct set of physiological and behavioural changes termed the acute sickness response. Although this response is universal, individuals differ considerably in terms of the overall severity and the specific manifestations of acute sickness symptoms – suggesting host determinants. We have previously reported a strong link between genetic variations in the intensity of the inflammatory response and the severity of the acute sickness across varied infections. Here we examined the impact of polymorphisms in cytokine [tumour necrosis factor (TNF)- α , interleukin (IL)-6, IL-10, interferon (IFN)- γ ; and the chemokine CCR5] and behavioural genes involved in the stress-response [neuropeptide Y (NPY) and monoamine oxidase A (MAOA)] on mood disturbance associated with infection in the Dubbo Infection Outcomes Study ( n = 296). Mood disturbance during infection was significantly increased by variants in cytokine genes that enhanced immune activity [IL-10-592A/C ( p = 0.04); IL-6-174 G/C ( p = 0.05); ‘wild type’ CCR5 ( p = 0.4)]; by several polymorphisms in the NPY gene linked to ‘low expression’ of NPY ( p s p = 0.03). In combination, immune and behavioural genes vulnerabilities acted synergistically to increase the likelihood of severe mood disturbance by up to 16-fold ( p = 0.004). These data provide novel insights into the complexity of genetic influences on the manifestations of the acute sickness response and shed light on the pathophysiology of post-infective depression.