Research

This large population-based study in Sweden investigated the potential link between severe infections and obsessive-compulsive disorder (OCD) through a familial co-aggregation approach. By analyzing data from over 4.9 million individuals born between 1960 and 2008, researchers explored the risk of OCD among relatives of those with severe infections, spanning varying degrees of genetic relatedness. The study found that the risk of OCD increased with closer genetic ties, with monozygotic twins showing the highest correlation. A dose-response relationship between the number of infections and the odds of OCD was also identified. These findings remained robust even after adjusting for comorbid autoimmune disorders and infections in relatives. The results suggest that genetic factors play a significant role in the observed association, pointing to shared genetic susceptibilities between infections and OCD. This supports the idea that genetic pleiotropy—where the same genes influence multiple traits—may contribute to both infection susceptibility and OCD risk. The study highlights the importance of considering both genetic and environmental factors in understanding OCD development.

Leonardi L, Perna C, Bernabei I, Fiore M, Ma M, Frankovich J, Tarani L, Spalice A. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Immunological Features Underpinning Controversial Entities. Children. 2024; 11(9):1043. https://doi.org/10.3390/children11091043

This study found that about a quarter of patients meeting strict PANS criteria who underwent lumbar punctures (LP) had cerebrospinal fluid (CSF) abnormalities, with the most common being elevated CSF protein and albumin quotient. These patients also exhibited signs of inflammation and autoimmunity, such as low complement levels, high immune complexes, non-specific autoantibodies, vasculopathy, and arthritis.

Interestingly, the “other psychiatric deterioration” group—those referred for PANS but not meeting strict criteria—had an even higher frequency (45%) of CSF abnormalities. Many of these patients also showed systemic inflammation, with conditions like thyroiditis and arthritis, and had symptoms overlapping with PANS, including obsessive-compulsive behaviors and food restrictions.

Both groups demonstrated a notable prevalence of arthritis, emphasizing systemic inflammation’s potential role, possibly affecting the blood-brain barrier (BBB). While the study was not designed to assess the significance of these differences, it suggests an overlap in psychiatric symptoms and inflammatory features across the groups, which may involve complement activation and vascular inflammation, similar to what’s seen in Long Covid.

• Children with PANS had lower levels of IgG antibodies (a type of immune protein) in their plasma during a symptom flare compared to matched controls.
• PANS IgG drawn at flare shows elevated binding to CINs in both mouse and human brain.
• PANS IgG binding to CINs reduces their activity using p-rpS6 as a marker.
• Reduction of PANS IgG binding to CINs parallels symptom improvement during recovery.
• Elevated IgG binding to CINs is resolved in the same subject during symptom recovery.
• The study suggests that at least a subset of PANS cases have a neuroimmune pathogenesis.

Whelan JP. Strep Throat and the Backstory for PANS and PANDAS. JAMA Netw Open. 2024;7(7):e2421636. doi:10.1001/jamanetworkopen.2024.21636

• Longitudinal analysis (Ma et al.) of 193 children with PANS revealed that 28% developed arthritis over 4 years, showing unusual rheumatic profiles like Achilles enthesitis (56%), inflammatory back pain (64%), and sacroiliac joint tenderness (69%). Only 2% had typical childhood arthritis.
• Back pain is a common concern among Whelan’s 600 families, often challenging to differentiate true spondyloarthropathy from pain amplification due to poor sleep, which almost all PANS patients experience.
• Ultrasonography in 40 children found effusions or synovitis, suggesting real back arthritis in many.
• A high prevalence of antihistone antibodies (20%) may result from multiple medications. 55% of children with PANS also had a coincident eating disorder.
• Frequent infections in two-thirds of these children may explain elevated inflammatory markers and the abrupt onset of tics, OCD, and behavioral issues, possibly due to “PANDA-genic” bacterial strains in genetically susceptible hosts.

Cardelle-Pérez, Federico & Greciano, María. (2024). PANDAS: Twenty-Five Years Later. Adolescent Psychiatry. 14. 10.2174/0122106766298492240320044542.

Discussion: A comprehensive approach, including interdisciplinary management and urgent evaluation of potential organic causes, is crucial for effective treatment. Treatment decisions should consider severity, symptoms, and available evidence. Collaboration with neuropediatric or neurological services is needed. ASLO/anti-DNase B and 25-OH-Vitamin D tests are valuable for atypical OCD/Tic presentations, always maintaining a broader organic screening.