Associations between childhood streptococcal upper respiratory infections and subsequent psychiatric outcomes have been described for over 25 years, although clinical evidence remains limited. This study explored psychiatric outcomes after pediatric streptococcal versus non-streptococcal upper respiratory tract infections.

This retrospective cohort study used TriNetX, a global federated health research network of over 150 million deidentified electronic medical records. We compared children aged 3–16 with a diagnosis of acute upper respiratory infection (ICD-10 J00-J06) and a Streptococcus pyogenes test result (positive or negative) within 2 weeks, propensity matched on 70 baseline variables. Main outcomes were the 1-year incidence of any psychiatric disorder, obsessive-compulsive disorder (OCD), tic disorder, anxiety, and restricted oral intake.

Before matching, 464,513 children were streptococcal positive and 1,023,171 children were streptococcal negative. After matching, there were 456,221 children in each cohort (48% female). The streptococcal-positive cohort had a reduced risk of any psychiatric disorder (RR 0.92 [0.90, 0.94]), restricted oral intake (0.81 [0.77, 0.86]), and anxiety disorder (0.94 [0.91, 0.97]) at 1 year. Risk of OCD (RR 0.98 [0.86, 1.12]) and tic disorder (RR 0.95 [0.87, 1.04]) was not significantly different between the two cohorts.

This large-scale cohort study found no evidence that exposure to S. pyogenes is associated with increased risk of the measured psychiatric outcomes.

Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this nationwide cohort study, we aimed to clarify the mechanisms underlying the association between proneness to infections and tic disorders.

Using Swedish national registers, we identified 3,886,533 individuals (probands) born between 1970 and 2008 with available data on both biological parents. Probands were linked to six clusters of relatives: parents, full siblings, maternal half-siblings, paternal half-siblings, aunts/uncles, and cousins. Cox proportional hazards regression models were used to estimate the risk of tic disorders in probands exposed to infections and their relatives, compared with unexposed probands and their relatives. We also examined dose–response associations using logistic regression models.

Probands exposed to infections had an increased risk of tic disorders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.40–1.52), as did their relatives. The observed risks increased with the degree of genetic relatedness, from HR (95% CI) of 1.15 (1.12–1.19) in cousins to 1.31 (1.25–1.37) in first-degree relatives. There was a dose–response association between the number of infections in the probands and the odds for tic disorders in the probands and their relatives. Results remained consistent after adjustment for infections in relatives, tic disorders in probands, and autoimmune diseases in probands and relatives.

Our results suggest an important role of shared genetic factors in the association between infections and tic disorders, potentially pointing to pleiotropic mechanisms.

An obsessive-compulsive disorder (OCD) subtype has been associated with streptococcal infections and is called pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). The neuroanatomical characterization of subjects with this disorder is crucial for the better understanding of its pathophysiology; also, evaluation of these features as classifiers between patients and controls is relevant to determine potential biomarkers and useful in clinical diagnosis. This was the first multivariate pattern analysis (MVPA) study on an early-onset OCD subtype.

Fourteen pediatric patients with PANDAS were paired with 14 healthy subjects and were scanned to obtain structural magnetic resonance images (MRI). We identified neuroanatomical differences between subjects with PANDAS and healthy controls using voxel-based morphometry, diffusion tensor imaging (DTI), and surface analysis. We investigated the usefulness of these neuroanatomical differences to classify patients with PANDAS using MVPA.

The pattern for the gray and white matter was significantly different between subjects with PANDAS and controls. Alterations emerged in the cortex, subcortex, and cerebellum. There were no significant group differences in DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) or cortical features (thickness, sulci, volume, curvature, and gyrification). The overall accuracy of 75% was achieved using the gray matter features to classify patients with PANDAS and healthy controls.

The results of this integrative study allow a better understanding of the neural substrates in this OCD subtype, suggesting that the anatomical gray matter characteristics could have an immune origin that might be helpful in patient classification.