title: Neurocognitive disturbances associated with acute infectious mononucleosis, Ross River fever and Q fever: a preliminary investigation of inflammatory and genetic correlates.
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-α and interferon-γ) and neurobehavioral genes (serotonin transporter and catechol-O-methyltransferase) were explored. 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). 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.
authors.affiliation: School of Psychiatry, University of New South Wales, Australia.
authors.forename: Erin
authors.initials: E
authors.lastname: Cvejic
authors.affiliation: School of Psychiatry, University of New South Wales, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Lemon
authors.affiliation: The Brain and Mind Research Institute, School of Psychiatry, University of Sydney, Australia.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Australia.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lloyd
authors.affiliation: School of Psychiatry, University of New South Wales, Australia. Electronic address: ute@unsw.edu.au.
authors.forename: Uté
authors.initials: U
authors.lastname: Vollmer-Conna
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018354:Alphavirus Infections / Q000150:complications*; D002097:C-Reactive Protein / Q000378:metabolism; D003072:Cognition Disorders / Q000150:complications* / Q000235:genetics*; D005260:Female; D006801:Humans; D007244:Infectious Mononucleosis / Q000150:complications*; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011778:Q Fever / Q000150:complications*; D012398:Ross River virus; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: Acute sickness response; Executive functioning; Genetic vulnerability; Inflammation; Interleukin-6; Neurocognitive performance; Polymorphisms