Genetic and inflammatory correlates of neurocognitive performance during naturally-occurring infective illness
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1
University of New South Wales, School of Psychiatry, Australia
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2
University of New South Wales, School of Medical Sciences, Australia
Background: Disturbances in neurocognitive performance are a core feature of the acute sickness response to infection; however the underlying mechanisms remain unclear.
Methods: A computerised battery was used 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 (glandular fever), Coxiella burnetii (the causative agent of Q fever), or Ross River virus (epidemic polyarthritis) until recovery. Subjects were assessed when ill, and a subset again after 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 [IFN]-γ) and neurobehavioral genes (serotonin transporter [5-HTT], 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 as well as levels of the inflammation marker, C-reactive protein (p = 0.03). Neurocognitive disturbances during acute illness were associated with functional polymorphisms: the high cytokine producing G allele of the IL-6-174G/C SNP was associated with poorer mental planning (p = 0.009, OR: 6.26) and the high producing T allele of the IFN-γ+874T/A SNP with poorer performance under dual attention conditions (p = 0.046, OR: 3.20). The homozygous, less active 5-HTT SS genotype was associated with slower Stroop task responses (p = 0.019, OR: 16.52).
Discussion: 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 evidence suggesting a role for a genetic predisposition to more intense inflammatory responses during infection and vulnerability in the serotonin system in objective neurocognitive disturbances during acute infections.
Acknowledgements
The project was funded in part by National Health and Medical Research Council of Australia (NHMRC) Project Grants (157062 and 157092), the Mason Foundation, and a Cooperative Research Agreement with the US Centres of Disease Control and Prevention (U50/CCU019851-01). AL is supported by a NHMRC Practitioner Fellowship (510246).
Keywords:
acute sickness response,
neurocognitive disturbances,
executive functioning,
Single nucleotide polymorphisms (SNPs),
Inflammation
Conference:
ACNS-2013 Australasian Cognitive Neuroscience Society Conference, Clayton, Melbourne, Australia, 28 Nov - 1 Dec, 2013.
Presentation Type:
Oral
Topic:
Executive Processes
Citation:
Cvejic
E,
Lloyd
A and
Vollmer-Conna
U
(2013). Genetic and inflammatory correlates of neurocognitive performance during naturally-occurring infective illness.
Conference Abstract:
ACNS-2013 Australasian Cognitive Neuroscience Society Conference.
doi: 10.3389/conf.fnhum.2013.212.00165
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Received:
15 Oct 2013;
Published Online:
25 Nov 2013.
*
Correspondence:
Dr. Erin Cvejic, University of New South Wales, School of Psychiatry, UNSW SYDNEY, NSW, 2052, Australia, erin.cvejic@sydney.edu.au