Research

The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness
Hornig M. The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr Opin Rheumatol. 2013 Jul;25(4):488-795. doi: 10.1097/BOR.0b013e32836208de. PMID: 23656715.

Summary: Microbes, both pathogenic and commensal, can induce autoantibodies that bind to brain and affect behavior in susceptible hosts. Interventions that correct the microbial balance or diminish autoantibody binding may be effective in diverse neuropsychiatric conditions mediated by autoimmunity.

Immune-mediated animal models of Tourette syndrome
Hornig M, Lipkin WI. Immune-mediated animal models of Tourette syndrome. Neurosci Biobehav Rev. 2013 Jul;37(6):1120-38. doi: 10.1016/j.neubiorev.2013.01.007.
“Demonstration of the ability to recreate these abnormalities through passive transfer of serum IgG from GAS-immunized mice into naïve mice and abrogation of this activity through depletion of IgG has provided compelling evidence in support of the autoimmune hypothesis. Immunologically-based animal models of TS are a potent tool for dissecting the pathogenesis of this serious neuropsychiatric syndrome.”
Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview

Rhee H, Cameron D. Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview. Int J Gen Med. 2012;5:163-174
https://doi.org/10.2147/IJGM.S24212

B. burgdorferi and GAβHS are very different microorganisms that evade the immune system and invade a wide variety of tissues, including the central nervous system (CNS). Lyme and PANS can have periods of active disease and periods of remission. Both infections cause physical, neurological, and cognitive symptoms.

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection
Yaddanapudi K, Hornig M, Serge R, De Miranda J, Baghban A, Villar G, Lipkin WI. Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Mol Psychiatry. 2010 Jul;15(7):712-26. doi: 10.1038/mp.2009.77.
Executive and Attention Functioning Among Children in the PANDAS Subgroup
Matthew E. Hirschtritt, Christopher J. Hammond, David Luckenbaugh, Jason Buhle, Audrey E. Thurm, B. J. Casey & Susan E. Swedo (2009) Executive and Attention Functioning Among Children in the PANDAS Subgroup, Child Neuropsychology, 15:2, 179-194, DOI: 10.1080/09297040802186899

Evidence from past studies indicates that adults and children with Obsessive-Compulsive Disorder (OCD) and Tourette syndrome (TS) experience subtle neuropsychological deficits. Less is known about neuropsychological functioning of children and adolescents with a symptom course consistent with the PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) subgroup of OCD and tics. T

  • Administered three tests of attention control and two of executive function to 67 children and adolescents (ages 5–16) diagnosed with OCD and/or tics and a symptom course consistent with the PANDAS subgroup and 98 healthy volunteers (HV) matched by age, sex, and IQ.
  • The PANDAS subjects were less accurate than HV in a test of response suppression.
  • In a two-step linear regression analysis of the PANDAS group in which clinical variables were added stepwise into the model and in the second step matching variables (age, sex, and IQ) were added, IQ emerged as a predictor of performance on this task.
  • ADHD diagnosis and age emerged as predictors of response time in a continuous performance task.
  • Subdividing the PANDAS group by primary psychiatric diagnosis revealed that subjects with TS or OCD with tics exhibited a longer response time compared to controls than subjects with OCD only
  • Children with PANDAS exhibit neuropsychological profiles similar to those of their primary psychiatric diagnosis.
Case Study: A New Infection-Triggered, Autoimmune Subtype of Pediatric OCD and Tourette’s Syndrome

Albert J. Allen MD, PhD, Henrietta L. Leonard, MD, Susan E. Swedo, MD
Journal of the American Academy of Child & Adolescent Psychiatry-1995

A review of clinical observations and literature reports leads to the hypothesis that, via a process analogous to Sydenham’s chorea, infections with group A β-hemolytic streptococci, among others, may trigger autoimmune responses that cause or exacerbate some cases of childhood-onset obsessive-compulsive disorder (OCD) or tic disorders (including Tourette’s syndrome).