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

Abstract

Epidemiological and animal research shows that maternal immune activation increases the risk of autism spectrum disorders (ASD) in offspring. Emerging evidence suggests that maternal immune conditions may play a role in the phenotypic expression of neurodevelopmental difficulties in children with ASD and this may be moderated by offspring sex. This study aimed to investigate whether maternal immune conditions were associated with increased severity of adverse neurodevelopmental outcomes in children with ASD. Maternal immune conditions were examined as predictors of ASD severity, behavioural and emotional well-being, and cognitive functioning in a cohort of 363 children with ASD (n = 363; 252 males, 111 females; median age 3.07 [interquartile range 2.64-3.36 years]). We also explored whether these outcomes varied between male and female children. Results showed that maternal asthma was the most common immune condition reported in mothers of children with ASD. A history of maternal immune conditions (p = 0.009) was more common in male children with ASD, compared to female children. Maternal immune conditions were associated with increased behavioural and emotional problems in male and female children. By contrast, maternal immune conditions were not associated with decreased cognitive function. The findings demonstrate that MIA may influence the expression of symptoms in children with ASD and outcomes may vary between males and females.

Early or Late Gestational Exposure to Maternal Immune Activation Alters Neurodevelopmental Trajectories in Mice: An Integrated Neuroimaging, Behavioral, and Transcriptional Study

“…Although we collected data for both male and female offspring, we may still have been underpowered to detect potentially subtle sexspecific effects. When comparing our two POL groups directly, we did observe greater alterations in male POL E offspring, which may indicate existence of subtle sex-effects (121,122). Surprisingly we did not observe any strong social deficits, often reported in MIA-offspring and central to ASD pathology (11,54,123).…”

Brain transcriptomic profiling reveals common alterations across neurodegenerative and psychiatric disorders

“…Correlation of transcriptomic alterations across brain regions demonstrated the limbic lobe captures the majority of transcriptomic similarity between Scz and BP, supporting the role of this region in mood and psychotic disorders 84 . Although the only region studied for PD was the frontal lobe, similar transcriptional changes were observed between PD-ASD, particularly for the genes involved in pathways such as neuroinflammation that has been recently linked to autism 85,86 . High frequency of parkinsonism has previously been reported in autistic cases 87 , in which inflammatory mechanisms are seemingly involved in the pathobiology of the disease 88,89 .…”

Histamine, Neuroinflammation and Neurodevelopment: A Review

“…Interestingly, this occurred in male rodents only and blockade of this stress response ameliorated any behavioral abnormalities associated with maternal immune activation, suggesting a sex-specific effect of maternal immune activation on neuroinflammation and neurodevelopment (Kalish et al, 2021). Indeed, autoimmune disorders (Patel et al, 2020) can lead to a similar sex-specific immune response. Furthermore, maternal neuronal autoantibodies have been associated with NDDs such as ASD (Dalton et al, 2003;Giannoccaro et al, 2019).…”