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. 2025 Aug 11;26(16):7767.
doi: 10.3390/ijms26167767.

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

Antonella Gagliano  1   2 , Francesca Cucinotta  3 , Ivana Giunta  4 , Irene Di Modica  4 , Carmela De Domenico  3 , Carola Costanza  2 , Eva Germanò  4 , Jennifer Frankovich  5   6
Affiliations

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

Antonella Gagliano et al. Int J Mol Sci. .

Abstract

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.

Keywords: PANS; neurodevelopmental disorders; neuroimmunology; neuroinflammation; pathogenetic pathways.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The PRISMA flow diagram indicating the process of selecting sources of evidence included in the scoping review. The numbers reported in the Record Identified reflect the cumulative results retrieved from three separate search strategies across two databases (PubMed and Web of Science) prior to the removal of duplicates.
Figure 2
Figure 2
A heat map summarizing the strength of immuno-inflammatory evidence across major neurodevelopmental disorders (NDDs) and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Evidence was extracted from Table 1 and graded on a 0–3 scale: 0 = no studies identified; 1 = limited or indirect evidence; 2 = moderate/conflicting evidence; 3 = strong or consistent evidence.
Figure 3
Figure 3
PANS: a syndromic constellation overlapping with other NDDs. Legend: NDDs: Neurodevelopmental Disorders; PANS: Pediatric Acute-Onset Neuropsychiatric Syndrome.
See this image and copyright information in PMC

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