A new analysis of from the original Dubbo studies that found a strong link to severity of initial infection (and cytokine genotype) with subsequent development of CFS. These findings look really interesting, but note the small sample size (given the number of tests), generally modest p values and acknowledged need to replicate. Neurocognitive disturbances associated with acute infectious mononucleosis, Ross River fever and Q fever: A preliminary investigation of inflammatory and genetic correlates Erin Cvejic a,Jim Lemon a,Ian B. Hickie b,Andrew R. Lloyd c,Uté Vollmer-Conna a Abstract Disturbances in neurocognitive performance are a core feature of the acute sickness response to infection; however the underlying mechanisms remain unclear. The current study used a computerised battery to assess neurocognitive functioning in subjects enrolled in the Dubbo Infection Outcomes Study (n = 107) – a prospective cohort of subjects followed from documented acute infection with Epstein Barr virus, Ross River virus, or Coxiella burnetii until recovery. Subjects were assessed when ill, and a subset again after complete recovery. Associations between sickness-related cognitive disturbances and single nucleotide polymorphisms (SNPs) in cytokine (interleukin [IL]-6, IL-10, tumor necrosis factor-? and interferon-?) and neurobehavioral genes (serotonin transporter and catechol-O-methyltransferase) were explored. Results During acute infection, subjects exhibited slower matching-to-sample responses (p = 0.03), poorer working memory capacity (p = 0.014), mental planning (p = 0.045), and dual attention task performance (p = 0.02), and required longer to complete discordant Stroop trials (p = 0.01) compared to recovery. Objective impairments correlated significantly with self-reported symptoms (p < 0.05) as well as levels of the inflammation marker, C-reactive protein (p = 0.001). Linear regression analysis identified an association between neurocognitive disturbance during acute illness and functional polymorphisms in inflammatory cytokine genes. Specifically, the high cytokine producing G allele of the IL-6-174G/C SNP was associated with poorer neurocognitive performance when subjects were ill (p = 0.027). Conclusion These findings confirm that acute infection impacts on neurocognitive performance, manifesting as slowed responses and impaired performance on complex tasks requiring higher-order functioning which has important real-world implications. The data provide the first preliminary evidence for a role of a genetic predisposition to more intense inflammatory responses in objective neurocognitive disturbances during acute infections. These associations require replication in a larger sample size.