Research

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

Fekete, R., Simats, A., Bíró, E., Pósfai, B., Cserép, C., Schwarcz, A., Szabadits, E., Környei, Z., Tóth, K., Fichó, E., Szalma, J., Vida, S., Kellermayer, A., Dávid, C., Acsády, L., Kontra, L., Silvestre-Roig, C., Moldvay, J., … Dénes, Á. (2025). Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19. Nature Neuroscience, 28(3), 558–576. DOI: 10.1038/s41593-025-01871-z

• Neuropathological study examining brains of individuals with COVID-19.

• Identifies microglial dysfunction, astrocyte involvement, and neurovascular inflammation linked to systemic IL-1 and IL-6 signaling.

• Demonstrates blood–brain barrier disruption and gliovascular pathology even in the absence of direct viral invasion of brain tissue.

• Provides strong evidence for self-sustaining inflammatory loops between peripheral immune signals and CNS cells.

Fekete R, Simats A, Bíró E, et al. Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19. Nat Neurosci. 2025;28(3):558-576. doi:10.1038/s41593-025-01871-z.

Impaired microglia function and vascular inflammation in COVID

• Observational study evaluating Long COVID patients treated with H1/H2 antihistamines.

• Reports improvement in fatigue, cognitive symptoms, tachycardia, and other systemic complaints.

• Supports the hypothesis that mast cell activation contributes to Long COVID symptom persistence.

• Suggests immune dysregulation—rather than viral persistence—may drive ongoing symptoms in a subset of patients.

Wu, X., Hao, J., Jiang, K. et al. Neuroinflammation and pathways that contribute to tourette syndrome. Ital J Pediatr 51, 63 (2025). https://doi.org/10.1186/s13052-025-01874-3

Read a deeper dive: Neuroinflammation and Immune Pathways in Tourette Syndrome

• Tourette Syndrome (TS): A neurodevelopmental disorder characterized by motor and vocal tics, often co-occurring with ADHD, OCD, and other psychological issues.
• Neurotransmitter Imbalances: TS is traditionally linked to neurotransmitter disruptions, especially within the cortex-striatum-thalamus-cortex circuit, involving dopamine and glutamate.
• Neuroinflammation: Emerging research shows neuroinflammation, often triggered by infections or allergies, contributes to neurotransmitter imbalances that may induce tics.
• Infectious Triggers: Streptococcal infections (e.g., PANDAS), viral infections (e.g., enterovirus, COVID-19), and other pathogens (e.g., Chlamydia, Mycoplasma) are linked to TS exacerbation.
• Immune Mechanisms: Inflammatory responses activate microglia and the peripheral immune system, disrupting neurotransmitter balance and leading to tics.

Tang AW, Swedo SE, Pasternack M, Murphy T, et al. Eight cases of pediatric acute-onset neuropsychiatric syndrome: clinical characteristics. Developmental Neuroscience. 2025;47(4):287–302. doi:10.1159/000543969

Please read more in depth blog – When PANS and IBD Co-Occur: What This Case Series Suggests

• Identifies a subgroup of children with PANS characterized by the triad of PANS symptoms, joint complaints, and family history of autoimmunity (including psoriasis).

• Suggests this subgroup may be at increased risk for inflammatory bowel disease and other immune-mediated disorders.

• Recommends a low threshold for evaluation of gastrointestinal inflammation using biomarkers such as hemoglobin, CRP, fecal calprotectin, and endoscopy when indicated.

• Reports that PANS symptoms may improve with effective treatment of inflammatory bowel disease.

• Notes high prevalence of joint complaints and autoimmune family history, suggesting shared immune mechanisms with psoriasis and arthritis.

• Proposes that treatments used in inflammatory bowel disease and arthritis warrant study for potential application in PANS.

Rachel Goren, Ari Bitnun, Asif Doja, Peter J Gill, Ronald M Laxer, Deborah M Levy, Tamara Pringsheim, Paul Sandor, Eluen Ann Yeh, Colin Wilbur, Sefi Kronenberg, Michelle Shouldice, Frequency and impact of paediatric acute-onset neuropsychiatric syndrome/paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections diagnosis in Canada, Paediatrics & Child Health, 2024;, pxae092, https://doi.org/10.1093/pch/pxae092

In a Canadian study, a significant percentage of children diagnosed with PANDAS/PANS had OCD and/or tics, with the majority experiencing at least two neuropsychiatric symptoms, and healthcare utilization was high, including emergency visits and inpatient admissions

• The Canadian Paediatric Surveillance Program estimated that the prevalence of PANS/PANDAS was 1 in 60,115 (0.0017%) for children ages 3 through 18 years
• The core diagnostic criteria of OCD, tics, or acute food refusal was absent in 12% of cases with 22% reporting sudden symptom onset
• Infection was associated with onset or exacerbation in less than 1 out of every 3 cases
• Most of the population exhibited 2+ neuropsychiatric symptoms with significant health care utilization amongst cases

• Initial Decline: Pediatric infections dropped during COVID-19 due to safety measures.
• Post-Pandemic Surge: Infections rebounded as restrictions eased, with changes in severity, strains, and affected age groups.
• Key Cause: Immunity debt from reduced exposure, not new variants or resistance.
• Impact: Unusual symptoms emerged, offering new insights into disease spread and progression.