Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome

Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterised by abrupt onset obsessive compulsive disorder and regression in neurodevelopmental skills, triggered by infection or stress. Whether PANS is a distinct entity or part of a neurodevelopmental spectrum is uncertain, and its pathophysiology remains unclear. We show that children with PANS (n = 32) and other non-PANS (n = 68) neurodevelopmental disorders (total n = 100) have higher reported early childhood infections and a loss of previously acquired developmental skills compared to neurotypical controls (n = 58). Children with PANS have normal routine immune testing, however bulk RNA-sequencing (PANS n = 20 vs controls n = 15) revealed upregulated pathways in ribosomal biogenesis and RNA methyltransferases, and downregulated pathways in diverse cellular functions such as mitochondrial activity, cell signalling, endocytosis, and immune responses. Single-cell RNA-sequencing (PANS n = 2 vs controls n = 2) confirmed these findings but showed heterogeneity across immune cell types. Toll-like receptor stimulation assay using peripheral blood mononuclear cells revealed reduced TNF and interleukin-6 responses in PANS patients (n = 7) compared to controls (n = 7). RNA sequencing before and after intravenous immunoglobulin treatment in PANS patients (n = 9 vs controls n = 10) revealed reversal of the dysregulated ribosomal, epigenetic, and cell signaling pathways. Given the central role of the immune system in synaptic pruning and neurodevelopment, these insights provide rationale for novel epigenetic and immune modulating therapies to optimize neurodevelopmental trajectories and minimize neuropsychiatric impairment in PANS.

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Publication Details

Journal
Molecular Psychiatry
Published
2025-08-30
DOI
https://doi.org/10.1038/s41380-025-03127-5
Citations
5
Primary Topic
Tryptophan and brain disorders
Type
article
Field-Weighted Citation Impact
2.89

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article

Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome

Iain Perkes, Wendy Gold, Shrujna Patel, Hiroya Nishida et al.
5 citations
Molecular Psychiatry
Tryptophan and brain disorders
2.89
article

Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome

Iain Perkes, Wendy Gold, Shrujna Patel, Hiroya Nishida, Brooke A. Keating, Brian Gloss, Fabienne Brilot, Emma Maple-Brown, Mark Evan Graham, Songyi Yuan, Sushil Bandodkar, Russell C. Dale, Markus J. Hofer, Sarah Alshammery, Ruwani Dissanayake, Nader Aryamanesh, Jingya Yan, Velda X. Han, Hannah Jones, Shekeeb S. Mohammad, Xianzhong Lau, Kavitha Kothur, Erica Tsang, Lee L. Marshall
article en
5 citations

Abstract

Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterised by abrupt onset obsessive compulsive disorder and regression in neurodevelopmental skills, triggered by infection or stress. Whether PANS is a distinct entity or part of a neurodevelopmental spectrum is uncertain, and its pathophysiology remains unclear. We show that children with PANS (n = 32) and other non-PANS (n = 68) neurodevelopmental disorders (total n = 100) have higher reported early childhood infections and a loss of previously acquired developmental skills compared to neurotypical controls (n = 58). Children with PANS have normal routine immune testing, however bulk RNA-sequencing (PANS n = 20 vs controls n = 15) revealed upregulated pathways in ribosomal biogenesis and RNA methyltransferases, and downregulated pathways in diverse cellular functions such as mitochondrial activity, cell signalling, endocytosis, and immune responses. Single-cell RNA-sequencing (PANS n = 2 vs controls n = 2) confirmed these findings but showed heterogeneity across immune cell types. Toll-like receptor stimulation assay using peripheral blood mononuclear cells revealed reduced TNF and interleukin-6 responses in PANS patients (n = 7) compared to controls (n = 7). RNA sequencing before and after intravenous immunoglobulin treatment in PANS patients (n = 9 vs controls n = 10) revealed reversal of the dysregulated ribosomal, epigenetic, and cell signaling pathways. Given the central role of the immune system in synaptic pruning and neurodevelopment, these insights provide rationale for novel epigenetic and immune modulating therapies to optimize neurodevelopmental trajectories and minimize neuropsychiatric impairment in PANS.

Molecular PsychiatryVol. 30(11)
The University of Sydney (AU), Children's Medical Research Institute (AU), National University of Singapore (SG), University of Wollongong (AU), Children's Hospital at Westmead (AU), UNSW Sydney (AU), Starship Children's Health (NZ), Westmead Institute for Medical Research (AU), Sydney Children’s Hospitals Network (AU), National University Health System (SG), AGRF Ltd (AU)
Children's Medical Research
Openalex Percentile: Top 9%
Tryptophan and brain disorders
2.89
DOIOpen Access PDFOpenAlex
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