Abstract

Background Systemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador.

Methods We examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least square regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes.

Results Higher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by −0.47 units (95% CI: −0.80, −0.13) and −0.42 (−0.72, −0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by −0.11 units (−0.19, −0.03). A unit increase in inflammatory composites of seven markers were associated with lower scores in language (−0.11 units, p=0.04), visuospatial processing (−0.15, p= 0.09), and social perception (−0.22, p=0.005) domains.

Conclusions Higher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Numbers (R01ES025792, R01ES030378, R21ES026084). B.N.C. Chronister was funded by the Institute of Mental Health (5T32MH122376).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The 2016 examination of the ESPINA study was approved by the Institutional Review Boards of the University of California San Diego (UCSD), Universidad San Francisco de Quito and the Ministry of Public Health of Ecuador and endorsed by the Commonwealth of Rural Parishes of Pedro Moncayo County. We collected informed consent from adult participants (aged 18 years or older) and parents, as well as parental permission of participation and informed assent of child participants.

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AbbreviationsCRPC-Reactive ProteinIL-6Interleukin-6TNF-⍺Tumor Necrosis Factor AlphasICAM-1soluble Intracellular Cell Adhesion Molecule-1sVCAM-1soluble Vascular Cell Adhesion Molecule-1SAASerum Amyloid ACD14Cluster of Differentiation 14