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.”
Increased IFNα Activity and Differential Antibody Response in Patients with a History of Lyme Disease and Persistent Cognitive Deficits
Jacek E, Fallon BA, Chandra A, Crow MK, Wormser GP, Alaedini A. Increased IFNα activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits. J Neuroimmunol. 2013 Feb 15;255(1-2):85-91. doi: 10.1016/j.jneuroim.2012.10.011. Epub 2012 Nov 8. PMID: 23141748; PMCID: PMC3557545.
The increase in IFNα activity is suggestive of a mechanism contributing to the ongoing neuropsychiatric symptoms.
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.

The Immunobiology of Tourette’s Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus, and Related Disorders: A Way Forward
Murphy TK, Kurlan R, Leckman J. The immunobiology of Tourette’s disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders: a way forward. J Child Adolesc Psychopharmacol. 2010 Aug;20(4):317-31. doi: 10.1089/cap.2010.0043. PMID: 20807070; PMCID: PMC4003464.

An infectious association to the onset of pediatric neuropsychiatric symptoms would certainly help explain the enigmatic changes that can quickly occur in an otherwise healthy child. Because many infections can seemingly be insignificantly present, their pathology is often underestimated. Host and pathogen traits likewise have the potential to alter neuroendocrine and neuroimmune responses that collectively contribute to neuropsychiatric disease formation.

It is time for the National Institutes of Health, in combination with advocacy and professional organizations, to convene a panel of experts not to debate the current data, but to chart a way forward. For now we have only to offer our standard therapies in treating OCD and tics, but one day we may have evidence that also allows us to add antibiotics or other immune-specific treatments to our armamentarium.

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.
Keeping acute rheumatic fever in the differential

HCP,

Read Article

In addition, patients may be emotionally labile and demonstrate crying, grimacing, or restlessness. Speech often is slurred. These emotional and behavioral changes tend to manifest before the choreiform motor movements. The latent period for chorea typically is longer than that observed with the other manifestations of ARF and seldom is evident at the initial presentation. A strong association has been demonstrated between infection with GAS and obsessive-compulsive and tic disorders.9

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.
Cognitive-Behavioral Therapy for PANDAS-Related Obsessive-Compulsive Disorder: Findings From a Preliminary Waitlist Controlled Open Trial
Storch EA, Murphy TK, Geffken GR, Mann G, Adkins J, Merlo LJ, Duke D, Munson M, Swaine Z, Goodman WK. Cognitive-behavioral therapy for PANDAS-related obsessive-compulsive disorder: findings from a preliminary waitlist controlled open trial. J Am Acad Child Adolesc Psychiatry. 2006 Oct;45(10):1171-8. doi: 10.1097/01.chi.0000231973.43966.a0. PMID: 17003662.

  • Six of seven children with PANDAS-related OCD improved after CBT; half maintained gains at follow-up.

  • Clinician-rated OCD and anxiety severity dropped significantly (large effect sizes: 3.38 and 2.29).

  • Self-reported anxiety and depression did not show significant changes.

  • Findings suggest CBT is a promising, safe, and minimally invasive treatment for PANDAS-related OCD.

Selective serotonin reuptake inhibitor-induced behavioral activation in the PANDAS subtype

Murphy, Tanya & Storch, Eric & Strawser, Melissa & Ba,. (2006). Selective serotonin reuptake inhibitor-induced behavioral activation in the PANDAS subtype. Primary Psychiatry. 13.

Although selective serotonin reuptake inhibitors (SSRI) are an effective and commonly used treatment for pediatric obsessive-compulsive disorder (OCD), their use has come under close scrutiny following reports of adverse reactions. The authors of this case report believe that children with the OCD subtype, pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS), may have increased vulnerability. The following report provides initial data on behavioral activation following SSRI use in 38 children with OCD of the PANDAS subtype. The authors use a particular case to highlight this issue and discuss treatment implications.

 

PANDAS With Catatonia: A Case Report. Therapeutic Response to Lorazepam and Plasmapheresis
Elia J, Dell ML, Friedman DF, Zimmerman RA, Balamuth N, Ahmed AA, Pati S. PANDAS with catatonia: a case report. Therapeutic response to lorazepam and plasmapheresis. J Am Acad Child Adolesc Psychiatry. 2005 Nov;44(11):1145-50. doi: 10.1097/01.chi.0000179056.54419.5e. PMID: 16239863.
  • Patient: 11-year-old boy with sudden urinary urgency, OCD, severe mood swings, inattention, impulsivity, hyperactivity, and intermittent immobilization.
  • Preceding Illness: Fever, cough, ear infection, sinusitis.
  • Findings: Elevated ASO & DNAse B titers; MRI showed caudate nuclei swelling.
  • Treatment & Outcome: Plasmapheresis rapidly improved OCD and reduced basal ganglia swelling, suggesting an immune-mediated process linked to strep.
  • Additional Note: ADHD-like symptoms improved with lorazepam, indicating possible catatonia.