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Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn Amygdala Phenotypes and Subsequent Behavior at 2 Years of Age

  • Alice M. Graham
    Affiliations
    Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon
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  • Jerod M. Rasmussen
    Affiliations
    Development, Health and Disease Research Program, University of California, Irvine, Irvine, California
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  • Marc D. Rudolph
    Affiliations
    Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon
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  • Christine M. Heim
    Affiliations
    Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Medical Psychology, Berlin, Germany

    Department of Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania
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  • John H. Gilmore
    Affiliations
    Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina
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  • Martin Styner
    Affiliations
    Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina
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  • Steven G. Potkin
    Affiliations
    Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, California
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  • Sonja Entringer
    Affiliations
    Development, Health and Disease Research Program, University of California, Irvine, Irvine, California

    Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Medical Psychology, Berlin, Germany
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  • Pathik D. Wadhwa
    Affiliations
    Development, Health and Disease Research Program, University of California, Irvine, Irvine, California
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  • Damien A. Fair
    Affiliations
    Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon

    Advanced Imaging Research Center, Oregon Health & Science University, Portland, Oregon
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  • Claudia Buss
    Correspondence
    Address correspondence to Claudia Buss, Ph.D., Department of Medical Psychology, Charité University of Medicine Berlin, Luisenstrasse 57, 10117 Berlin, Germany.
    Affiliations
    Development, Health and Disease Research Program, University of California, Irvine, Irvine, California

    Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Medical Psychology, Berlin, Germany
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      Abstract

      Background

      Maternal inflammation during pregnancy increases the risk for offspring psychiatric disorders and other adverse long-term health outcomes. The influence of inflammation on the developing fetal brain is hypothesized as one potential mechanism but has not been examined in humans.

      Methods

      Participants were adult women (N = 86) who were recruited during early pregnancy and whose offspring were born after 34 weeks’ gestation. A biological indicator of maternal inflammation (interleukin-6) that has been shown to influence fetal brain development in animal models was quantified serially in early, mid-, and late pregnancy. Structural and functional brain magnetic resonance imaging scans were acquired in neonates shortly after birth. Infants’ amygdalae were individually segmented for measures of volume and as seeds for resting state functional connectivity. At 24 months of age, children completed a snack delay task to assess impulse control.

      Results

      Higher average maternal interleukin-6 concentration during pregnancy was prospectively associated with larger right amygdala volume and stronger bilateral amygdala connectivity to brain regions involved in sensory processing and integration (fusiform, somatosensory cortex, and thalamus), salience detection (anterior insula), and learning and memory (caudate and parahippocampal gyrus). Larger newborn right amygdala volume and stronger left amygdala connectivity were in turn associated with lower impulse control at 24 months of age, and mediated the association between higher maternal interleukin-6 concentrations and lower impulse control.

      Conclusions

      These findings provide new evidence in humans linking maternal inflammation during pregnancy with newborn brain and emerging behavioral phenotypes relevant for psychiatric disorders. A better understanding of intrauterine conditions that influence offspring disease susceptibility is warranted to inform targeted early intervention and prevention efforts.

      Keywords

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