Inflammation in early childhood has been shown to impact brain development and increase the risk of autism spectrum disorders (ASD) and schizophrenia, according to new research from the University of Maryland School of Medicine (UMSOM). The study, led by researchers Seth Ament and Margaret McCarthy, focused on how inflammation can trigger epigenetic changes in brain regions associated with higher cognitive functions, potentially contributing to a range of neuropsychiatric disorders.
While the immune system is essential for protecting the body from pathogens, inflammation can sometimes cause collateral damage or even lead to chronic autoimmune diseases. Previous studies have also linked maternal inflammation during pregnancy to an increased risk of autism and schizophrenia in children. However, it was unclear whether these inflammatory responses continue to disrupt neurodevelopment throughout a child’s early years, and the mechanisms by which inflammation affects brain development were not well understood.
The UMSOM study collected post-mortem brain tissue from 17 deceased children, with half of the subjects having died during acute inflammation and the other half from accidents. The research focused on epigenetic changes in the cerebellum, one of the first brain regions to develop and one of the last to reach maturity. The study utilized single nucleus RNA sequencing technology to examine changes at the cellular level.
The findings revealed that inflammation affected two types of cerebellar neurons: Golgi and Purkinje neurons. Although these cell types are relatively rare, they play critical roles in cognition and behavior. Golgi neurons coordinate communication within the cerebellum, while Purkinje neurons form synapses connecting the cerebellum to other brain regions involved in cognitive and emotional control. Disruption of these developmental processes could explain how inflammation contributes to conditions like ASD and schizophrenia.
The study found that inflammation caused epigenetic changes consistent with the downregulation of developmental gene expression programs in the affected cells. This suggests that inflammation could inhibit the maturation of critical brain regions involved in cognition and behavior.
According to Maureen Cowan, a scientist from the University of Virginia who specializes in neuroinflammation, the study’s results indicate that there are shared molecular signals in different types of inflammation, which can contribute to underlying neuronal dysfunction in the developing brain. However, the study focused on acute inflammation, and it remains unclear whether the findings also apply to milder chronic inflammation.
The researchers caution that inflammation is just one of many factors that contribute to the development of neuropsychiatric disorders. Factors such as genetics and environment also play significant roles. Nonetheless, the study provides evidence of how inflammation can contribute to dysfunctional brain development, highlighting the broader role of inflammation in neurological disease.
The researchers believe that the vulnerability to inflammation’s effects on cerebellum development is greatest around the age of 12 months. However, further studies are needed to fully understand the time courses and impacts of inflammation on neurodevelopment in infants and older children.
The study underscores the importance of understanding the complex interplay between the immune system, inflammation, and brain development in order to better prevent and treat neurodevelopmental disorders. By identifying the role of inflammation in these conditions, researchers are one step closer to unveiling potential therapeutic targets for ASD and schizophrenia.
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1. Source: Coherent Market Insights, Public sources, Desk research
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