Increasing Role of Maternal Immune Activation in Neurodevelopmental Disorders

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.

The SARS-CoV-2 and mental health: From biological mechanisms to social consequences

“…Although, according to the available reports, pregnant women are at low risk of unfavorable outcomes of the SARS-CoV-2 infection, these conclusions might be premature ( Sominsky et al, 2020 ). At this point, it is of great importance that non-specific maternal immune activation might also be associated with impaired neurodevelopmental trajectories in the offspring ( Boulanger-Bertolus et al, 2018 ).…”

Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive co-morbidity

“…Increasing evidence suggests that immune system dysregulation [8][9][10][11] , particularly maternal immune activation (MIA) [12][13][14] , is one factor that may be involved in the pathophysiology of ASD and other neurodevelopmental disorders. An extensive body of preclinical research has provided substantial evidence for the MIA hypothesis in ASD [15][16][17][18] .…”

Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease

“…This is consistent with the idea that early-life environmental exposures might affect later risk for psychiatric disorders through effects on the immune system. Research using maternal immune activation model(s) provides some support for this general idea, as do studies of exposure to chronic stress [126,127]. Many chemical exposures are also known to interact with immune pathways and molecules, or contribute to the development of abnormal immune responses such as braindirected autoimmune reactions, yet the linkage to alterations in brain development and the implications for psychiatric conditions remain largely unexplored [128][129][130][131].…”