Biomarkers for Diagnosis and Treatment Response in Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a complex neuropsychiatric disorder characterized by the abrupt onset of symptoms and currently diagnosed mainly on clinical criteria, as reliable diagnostic biomarkers are still lacking. The primary objective of this project is to identify and validate a panel of neurophysiological, molecular, genetic, and metabolomic biomarkers associated with disease onset, clinical trajectory, and response to antimicrobial, anti-inflammatory, and immunomodulatory treatments. Identifying objective biomarkers will improve diagnostic accuracy, facilitate earlier diagnosis, clarify disease mechanisms, and support the development of more targeted therapeutic strategies. PANS is currently considered a multifactorial immune-mediated inflammatory brain disorder resulting from the interaction of genetic susceptibility, immune dysregulation, infections, and environmental factors such as stress or trauma. Current evidence suggests that both innate and adaptive immune responses contribute to disease pathophysiology through interactions between the peripheral immune system and the central nervous system. The pathogenic process may begin during fetal life through Maternal Immune Activation (MIA), whereby maternal infections or immune dysregulation induce inflammatory responses that increase susceptibility to neurodevelopmental disorders. During the postnatal period, infectious agents, including viruses, Mycoplasma pneumoniae, and Haemophilus influenzae, may trigger immune activation, leading to blood-brain barrier disruption, glial activation, and abnormalities within cortico-basal ganglia circuits thought to underlie PANS symptoms. To achieve these objectives, the project will adopt a multidisciplinary translational approach that combines the enrolment and characterization of pediatric patients with PANS with complementary studies in animal models. Particular emphasis will be placed on clinical and sleep features, together with mol