Increasing Role of Maternal Immune Activation in Neurodevelopmental Disorders.

Julie Boulanger-Bertolus,Carlo Pancaro,George A Mashour

doi:10.3389/fnbeh.2018.00230

Julie Boulanger-Bertolus, Carlo Pancaro + Show 1 more

Open Access

https://doi.org/10.3389/fnbeh.2018.00230

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Abstract

The earliest stages of development are critically sensitive to environmental insults. An unfortunately timed stress on the developing brain can have dramatic consequences for the neurodevelopment and future mental health of the individual. In particular, infection of the mother during pregnancy has been correlated with increased risk of psychiatric and neurodevelopmental disorders. Evidence suggests that maternal immune activation, independently from the infection itself, can be responsible for the outcome in the offspring. This recognition has resulted in expanding study designs from epidemiologic correlations to the search for a causal relationship between activation of the maternal immune system and cognitive consequences for the offspring. However, this causality analysis remained limited in humans until recent work that longitudinally linked specific markers of maternal inflammation during pregnancy with alterations of the newborn brain and cognitive development of toddlers. This focused narrative review compares and discusses the results of these recent studies and places them into the broader landscape of maternal immune activation literature. New data point, in particular, to the association between the levels of interleukin 6 (IL-6) and modifications of the offspring’s salience network and subsequent cognitive impairments. This article further emphasizes the need to carefully control for potential confounders in studying the effects of maternal immune activation on the neonatal brain as well as the under-investigated consequences of intra-partum fever on offspring neurodevelopment.

Highlights

Maternal Immune Activation and Neurodevelopment. These observations further established a causal link between maternal immune activation during pregnancy and changes in the offspring that mimic the symptoms of psychopathologies such as autism spectrum disorder or schizophrenia
A broader context for the results of Spann et al (2018) is established by comparing them to three studies that investigated the same population of mother-child dyads at the University of California Irvine (UCI), correlating the levels of interleukin 6 (IL-6) during early, mid and late pregnancy to characteristics of the neonate’s brain measured when the infant was sleeping in the scanner (Graham et al, 2018; Rasmussen et al, 2018; Rudolph et al, 2018; Figure 2)
The average level of maternal IL-6 during pregnancy was associated with modifications of the: (1) volume of the right amygdala, and of the connectivity between bilateral amygdala and regions involved in sensory processing and integration, salience detection, and learning and memory, as measured using whole-brain analysis (Graham et al, 2018); (2) fronto-limbic microstructural maturation, as estimated from the fractional anisotropy of water diffusing in the brain (Rasmussen et al, 2018); and (3) functional connectivity within the salience network and between structures involving the subcortical network, the salience network and the dorsal attention network, as measured by pairwise correlations of activity within or between 264 regions of interest belonging to larger networks or communities (Rudolph et al, 2018)

Summary

Introduction

Human studies associating prenatal concentration of those factors, offspring brain development alteration and behavioral outcomes are still limited and would be crucial to better understand the consequences of maternal immune activation on the developing brain. These studies had a similar longitudinal design by measuring the levels of inflammatory markers during pregnancy, followed by a correlation of those markers to network development using functional magnetic resonance imaging of the brain (Figure 2).

Results

Conclusion