Association of Streptococcal Throat Infection With Mental Disorders: Testing Key Aspects of the PANDAS Hypothesis in a Nationwide Study

Abstract

Importance: Streptococcal infection has been linked with the development of obsessive-compulsive disorder (OCD) and tic disorders, a concept termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). However, previous studies of this association have been small, and the results have been conflicting.

Objective: To investigate the risk of mental disorders, specifically OCD and tic disorders, after a streptococcal throat infection.

Design, setting, and participants: A population-based cohort study was conducted using data from the nationwide Danish registers from January 1, 1996, to December 31, 2013, with up to 17 years of follow-up. The Danish National Health Service Register provided information on individuals with the registration of a streptococcal test. Data analysis was conducted from January 1, 2016, to February 28, 2017.

Main outcomes and measures: Individuals were followed up in the nationwide Psychiatric Central Register for a diagnosis of any mental disorder, OCD, or tic disorders. Incidence rate ratios (IRRs) were calculated by Poisson regression analysis.

Results: Of the 1 067 743 children (<18 years of age) included in the study (519 821 girls and 547 922 boys), 638 265 received a streptococcal test, 349 982 of whom had positive test results at least once. Individuals with a positive streptococcal test result had an increased risk of any mental disorder (n = 15 408; IRR, 1.18; 95% CI, 1.15-1.21; P < .001), particularly of OCD (n = 556; IRR, 1.51; 95% CI, 1.28-1.77; P < .001) and tic disorders (n = 993; IRR, 1.35; 95% CI, 1.21-1.50; P < .001), compared with individuals without a streptococcal test. Furthermore, the risk of any mental disorder and OCD was more elevated after a streptococcal throat infection than after a nonstreptococcal infection. Nonetheless, individuals with a nonstreptococcal throat infection also had an increased risk of any mental disorder (n = 11 315; IRR, 1.08; 95% CI, 1.06-1.11; P < .001), OCD (n = 316; IRR, 1.28; 95% CI, 1.07-1.53; P = .006), and tic disorders (n = 662; IRR, 1.25; 95% CI, 1.12-1.41; P < .001).

Conclusions and relevance: This large-scale study investigating key aspects of the PANDAS hypothesis found that individuals with a streptococcal throat infection had elevated risks of mental disorders, particularly OCD and tic disorders. However, nonstreptococcal throat infection was also associated with increased risks, although less than streptococcal infections for OCD and any mental disorder, which could also support important elements of the diagnostic concept of pediatric acute-onset neuropsychiatric syndrome.

Figure.. Risk of Mental Disorders in Individuals With Positive or Negative Streptococcal Test Results Compared With Individuals Who Did Not Undergo Streptococcal Tests

Individuals with positive or negative streptococcal test results had a significantly increased risk of any mental disorder, obsessive-compulsive disorder (OCD), and tic disorders compared with individuals who did not undergo a test. However, the risk of any mental disorder (incidence rate ratio [IRR], 1.18; 95% CI, 1.15-1.21; P < .001) and OCD (IRR, 1.51; 95% CI, 1.28-1.77; P = .03) was still largest in individuals with positive test results compared with individuals with negative test results (any mental disorder: IRR, 1.08; 95% CI, 1.06-1.11; and OCD: IRR, 1.28; 95%CI, 1.07-1.53).The streptococcal test was the rapid antigen diagnostic test for group A β-hemolytic streptococcal throat infections. The incidence rate ratio was adjusted for sex, age, and calendar year. Error bars indicate 95% CIs.