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

Han VX, Alshammery S, Keating BA, Gloss BS, Hofer MJ, Graham ME, Aryamanesh N, Marshall LL, Yuan S, Maple-Brown E, Yan J, Bandodkar S, Kothur K, Nishida H, Jones H, Tsang E, Lau X, Dissanayake R, Perkes I, Mohammad SS, Brilot F, Gold W, Patel S, Dale RC, et al. Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome. Molecular Psychiatry. 2025;30:5389–5404. doi:10.1038/s41380-025-03127-5

  • Compared children with PANS and other neurodevelopmental disorders to neurotypical controls; PANS/non-PANS groups reported more early childhood infections and loss of previously acquired developmental skills than controls.

  • Found routine immune testing largely normal, but RNA sequencing showed upregulated ribosomal biogenesis/RNA methyltransferase pathways and downregulated mitochondrial, signaling, endocytosis, and immune pathways.

  • Toll-like receptor stimulation showed reduced TNF and IL-6 responses in PANS; post-IVIG RNA sequencing demonstrated partial normalization of dysregulated pathways.

  • Authors conclude findings support immune and epigenetic dysregulation in PANS and provide rationale for immune-modulating therapies.

Pediatric acute neuropsychiatric syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal Infections (PANDAS) in the Context of EMTICS: Methodological Considerations and Misinterpretations

Turowski, P., Fetz, K., Chang, K. et al. Pediatric acute neuropsychiatric syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal Infections (PANDAS) in the Context of EMTICS: Methodological Considerations and Misinterpretations. Eur Child Adolesc Psychiatry 34, 3685–3688 (2025). https://doi.org/10.1007/s00787-025-02747-0

“With the identification of biological markers, distinctions between syndromes like PANS and PANDAS may become clinically obsolete, shifting focus to underlying mechanisms rather than clinical presentation.” The authors argue that current labels like PANS and PANDAS are largely symptom-based frameworks that exist because we lack definitive biological tests. As research identifies reliable biomarkers such as immune signatures, autoantibodies, or inflammatory pathways, these distinctions may become less clinically relevant. Instead of categorizing patients by how symptoms present or which trigger is suspected, diagnosis and treatment could shift toward the underlying biological mechanisms driving illness, allowing for more precise, mechanism-based care rather than reliance on descriptive clinical syndromes.

  • EMTICS (European Multicentre Tics in Children Studies) is a large longitudinal study designed to examine environmental risk factors for tic disorders, not to diagnose or test PANS or PANDAS which was not designed, powered, or structured to evaluate PANS/PANDAS, so using it to dismiss these conditions is methodologically incorrect.
  • EMTICS did not systematically assess PANS/PANDAS clinical criteria or timing of infections relative to symptom changes.
REM sleep atonia in patients with pediatric acute-onset neuropsychiatric syndrome: implications for pathophysiology
Congiu P, Gagliano A, Carucci S, Lanza G, Ferri R, Puligheddu M. REM sleep atonia in patients with pediatric acute-onset neuropsychiatric syndrome: implications for pathophysiology. J Clin Sleep Med. 2025 May 1;21(5):757-764. doi: 10.5664/jcsm.11544. PMID: 39745443; PMCID: PMC12048332.

  • Sleep disturbance occurs in up to 80% of children with PANS.
  • Study compared 69 PANS patients to 44 age- and sex-matched controls using polysomnography.
  • REM atonia index (RAI) was significantly lower in PANS patients.
  • 25 of 57 PANS patients had abnormally low RAI vs 1 of 43 controls.
  • Normal age-related increase in REM atonia seen in controls was absent in PANS.
  • Takeaway: Reduced REM atonia in PANS suggests brainstem dysfunction affecting REM sleep
Immunological drivers and potential novel drug targets for major psychiatric, neurodevelopmental, and neurodegenerative conditions

Dardani, C., Robinson, J.W., Jones, H.J. et al. Immunological drivers and potential novel drug targets for major psychiatric, neurodevelopmental, and neurodegenerative conditions. Mol Psychiatry 30, 4487–4496 (2025). https://doi.org/10.1038/s41380-025-03032-x

  • Study used Mendelian randomization and genetic colocalisation to assess causality between immune biomarkers and neuropsychiatric disease
  • 736 immune-related biomarkers were analyzed across blood and brain tissue
  • Evidence supported a potential causal role for 29 immune biomarkers across 7 neuropsychiatric conditions
  • Findings implicate both systemic and brain-specific immune mechanisms in schizophrenia, Alzheimer’s disease, depression, and bipolar disorder
  • 20 identified biomarkers are therapeutically actionable, including ACE, TNFRSF17, SERPING1, AGER, and CD40
  • Results help prioritize immune targets for future mechanistic studies and treatment development, though causality requires further validation