Evaluation of maternal inflammation as a marker of future offspring ADHD symptoms: A prospective investigation

Hanna C. Gustafsson, Elinor L. Sullivan, Eleanor A.J. Battison, Kathleen F. Holton, Alice M. Graham, Sarah L. Karalunas, Damien A. Fair, Jennifer M. Loftis, Joel T. Nigg

Research output: Contribution to journalArticlepeer-review

Abstract

Early life predictors of attention-deficit/hyperactivity disorder (ADHD) are critically needed; they could inform etiological theory and may help identify new prevention targets. The current study examined prospectively whether maternal cytokine levels during pregnancy predict offspring ADHD symptoms at age 4–6 years. Secondarily, we evaluated maternal cytokine levels as a possible common pathway through which prenatal risks exert influence on child ADHD. Data came from a sample of women recruited during the 2nd trimester of pregnancy (N = 62) and followed postnatally until children were 4–6 years old. Maternal inflammation was assessed using 3rd trimester plasma concentrations of three indicators of nuclear factor kappa B signaling: interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 which were combined into a latent variable. Mothers and teachers reported on child ADHD symptoms, negative affect, and externalizing behaviors at 48–72 months of age. Maternal inflammation in the 3rd trimester predicted ADHD symptoms when children were 4–6 years old (β = 0.53, 95% CI = 0.154, 0.905, p = 0.006). Further, maternal inflammation mediated the effect of prenatal distress on child ADHD (β = 0.21, 95% CI = 0.007, 0.419, p = 0.04). The inflammation effect on ADHD was not explained by concurrent child negative affect, externalizing behavior, or familial ADHD status. This is the first human study to prospectively link maternal pregnancy cytokine levels and offspring ADHD symptoms, suggesting that cytokine levels are a possible marker of ADHD risk. Results also provide new evidence that maternal prenatal inflammation may be one common pathway by which prenatal risk factors influence offspring mental health outcomes.

Original languageEnglish (US)
Pages (from-to)350-356
Number of pages7
JournalBrain, Behavior, and Immunity
Volume89
DOIs
StatePublished - Oct 2020
Externally publishedYes

Bibliographical note

Funding Information:
Research reported in this publication was supported by the Abracadabra Foundation, the Moore Institute for Nutrition and Wellness, and by the National Institutes of Health under National Institute of Mental Health award numbers R3759105 (Nigg), R01MH117177 (Sullivan and Nigg) and K01MH120507 (Gustafsson), and the National Center for Advancing Translational Sciences award number TL1TR002371 (Gustafsson). The funding sources had no role in the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit the article for publication. This material is the result of work supported with resources and the use of facilities at the VA Portland Health Care System, Portland, OR. Dr. Loftis is an employee of the U.S. Department of Veterans Affairs. Contents do not necessarily represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Funding Information:
Research reported in this publication was supported by the Abracadabra Foundation, the Moore Institute for Nutrition and Wellness, and by the National Institutes of Health under National Institute of Mental Health award numbers R3759105 (Nigg), R01MH117177 (Sullivan and Nigg) and K01MH120507 (Gustafsson), and the National Center for Advancing Translational Sciences award number TL1TR002371 (Gustafsson). The funding sources had no role in the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit the article for publication. This material is the result of work supported with resources and the use of facilities at the VA Portland Health Care System, Portland, OR. Dr. Loftis is an employee of the U.S. Department of Veterans Affairs. Contents do not necessarily represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • ADHD
  • Cytokines
  • Inflammation
  • Prenatal distress

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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