Maternal Interleukin-6 Is Associated With Macaque Offspring Amygdala Development and Behavior

Julian S B Ramirez, Alice M Graham, Jacqueline R Thompson, Jennifer Y Zhu, Darrick Sturgeon, Jennifer L Bagley, Elina Thomas, Samantha Papadakis, Muhammed Bah, Anders Perrone, Eric Earl, Oscar Miranda-Dominguez, Eric Feczko, Eric J Fombonne, David G Amaral, Joel T Nigg, Elinor L Sullivan, Damien A Fair

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18 Scopus citations


Human and animal cross-sectional studies have shown that maternal levels of the inflammatory cytokine interleukin-6 (IL-6) may compromise brain phenotypes assessed at single time points. However, how maternal IL-6 associates with the trajectory of brain development remains unclear. We investigated whether maternal IL-6 levels during pregnancy relate to offspring amygdala volume development and anxiety-like behavior in Japanese macaques. Magnetic resonance imaging (MRI) was administered to 39 Japanese macaque offspring (Female: 18), providing at least one or more time points at 4, 11, 21, and 36 months of age with a behavioral assessment at 11 months of age. Increased maternal third trimester plasma IL-6 levels were associated with offspring's smaller left amygdala volume at 4 months, but with more rapid amygdala growth from 4 to 36 months. Maternal IL-6 predicted offspring anxiety-like behavior at 11 months, which was mediated by reduced amygdala volumes in the model's intercept (i.e., 4 months). The results increase our understanding of the role of maternal inflammation in the development of neurobehavioral disorders by detailing the associations of a commonly examined inflammatory indicator, IL-6, on amygdala volume growth over time, and anxiety-like behavior.

Original languageEnglish (US)
Pages (from-to)1573-1585
Number of pages13
JournalCerebral cortex (New York, N.Y. : 1991)
Issue number3
StatePublished - Mar 14 2020

Bibliographical note

Funding Information:
This work was supported by the National Institute of Health (R01 MH115357 to D.A.F. and J.T.N and R01 MH096773 to D.A.F., and P60 AA010760 to D.A.F. and T.P., and R01 MH107508 to E.L.S. and R01MH105538 to MPI: C. Buss, P. Wadhwa & D.A.F. and MHR3759107 to J.T.N. and R00 MH111805 to A.M.G and UL1GM118964, RL5GM118963, and TL4GM118965 to M.B.) and the National Library of Medicine (T15LM007088 to E.F.) and P51 OD011092 (ONPRC Core grant for support of the animals), and Bill & Melinda Gates Foundation to D.A.F., and DeStefano Family Foundation to D.A.F.

Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail:

PubMed: MeSH publication types

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


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