The Immune/Inflammatory Underpinnings of Neurodevelopmental Disorders and Pediatric Acute-Onset Neuropsychiatric Syndrome: A Scoping Review

Among the shared pathogenetic mechanisms leading to neurodevelopmental disorders (NDDs), a dysregulated inflammatory response has been described as a convergent pathway in NDDs. This scoping review was registered in the OSF database. It was conducted in accordance with the PRISMA Extension for Scoping Reviews, utilizing a comprehensive literature search of major academic databases, including PubMed and Web of Science. The search was performed until 1 March 2025, using a combination of predefined search terms and Boolean operators (AND, OR) to ensure a comprehensive identification of relevant studies. A comprehensive summary of the evidence on immunological and neuroinflammatory pathways underlying the NDDs is shown. This review also reports evidence on early-onset presentation of schizophrenia spectrum and obsessive-compulsive disorder since clinical researchers are beginning to consider these conditions neurodevelopmental disorders. Furthermore, this review outlines the recently described clinical entity, PANS (Pediatric Acute-Onset Neuropsychiatric Syndrome), and its clinical and pathogenetic contact points with NDDs, delineating a spectrum of disorders that share common pathogenetic pathways. This scoping review improves the awareness of immune/neuroinflammatory correlates supporting NDDs. Furthermore, it suggests adopting a transnosographic approach to neuropsychiatric disorders, including PANS as a syndromic construct that overlaps with NDDs.