The Inflamed Brain: Mapping Microglial Dysfunction in Autism Spectrum Disorder

Recent research suggests chronic neuroinflammation, particularly via microglial activation, contributes to disrupted neural connectivity and Autism Spectrum Disorder progression. However, a comprehensive quantitative mapping of how microglial research in Autism Spectrum Disorder has evolved over time, and where critical knowledge gaps remain, is lacking. An initial Web of Science search yielded 288 articles. The top 100 most-cited papers were selected to capture foundational, high-impact studies shaping the field's clinical trajectory. RStudio and Biblioshiny were used to analyze metadata on authorship, institutional affiliations, citations, journals, and keywords to evaluate publication trends, influential contributors, and thematic evolution. Results demonstrated a clear thematic transition from broad cytokine profiling toward mechanistic investigations of microglial activation, immune signaling, and synaptic dysfunction. Keyword co-occurrence network analysis, literature review, and thematic mapping revealed critical gaps, specifically an overrepresentation of preclinical animal models alongside underdeveloped clinical and longitudinal human studies. Furthermore, mapping established versus emerging themes highlighted a lack of standardized biomarkers connecting cellular neuroinflammation to specific Autism Spectrum Disorder behavioral phenotypes. Overall, Autism Spectrum Disorder research is shifting from broad inflammatory associations toward targeted cellular pathways. Identifying specific neuroimmune pathways provides actionable targets for precision medicine, emphasizing the need for translational human research.