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Psychiatric Disorders in First-Degree Relatives of Children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) 3
(A journal article by Lougee, Perlmutter, Nicolson, Garvey, and Swedo) 

This Article Review is presented by Patrick W. Joyner, M.S.

 The Pennsylvania State University – College of Medicine


Introduction:  The goal of this article is to determine the rates of psychiatric disorders in the first-degree relatives of children with obsessive-compulsive disorder (OCD) and/or tics secondary to a Group A β-hemolytic Streptococcus (GABHS) infection.


Hypothesis:  The rates of OCD and tic disorders would be increased among the first-degree relatives of the PANDAS probands and that the findings would replicate previous family studies of probands with OCD and/or tic disorders; but not isolated to the PANDAS subgroup.


  1. What is PANDAS?
  2. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections.
  3. More specifically, a subgroup of pediatric patients with the sudden onset and/or acute exacerbations of tics and/or obsessive-compulsive symptoms that follow infections with GABHS.
  4.                                                               This subgroup is unique in age of presenting symptoms (3-12 years old)
  5.                                                             The course of their symptoms; relapsing and remitting (i.e. sawtooth pattern if graphed longitudinally).

iii.      Presence of choreiform movements (95% in acutely ill patients).

  1. Choreiform Movements – an isolated finding of fine piano playing movements of the fingers that is not present at rest and only elicited via stressed postures.
  2. Choreatic Movements (i.e. Syndenham’s Chorea) – writhing adventitious movements that are accompanied by a failure to sustain tetanic contractions and muscle weakness; as well are present continuously and increase with unrelated voluntary movements.
  3.                                                           Abrupt onset of symptoms (an overnight explosion of symptoms that can become clinically significant and require emergency treatment in 24-48 hours).
  4. Hypothesis of PANDAS pathogenesis:
  5. 2000 – PANDAS symptoms are expressed when the environmental trigger for OCD and/or tic disorder (i.e. GABHS) affects children whom are vulnerable genetically.
  6. 2004 – GABHS is the etiologic variable responsible for the OCD and/or tics associated with PANDAS.  However, other factors play a role in regards to the susceptibility of symptoms following GABHS infections such as:  1.  pathologic strains of GABHS, 2.  host susceptibility (i.e. genetic, developmental, and social), and 3.  abnormal immune system responsivity.
  7. Figure of Pathogenesis of PANDAS:

Reprinted with permission of the author

III.             Study Subjects

  1. 54 children (42♂ & 12♀) with PANDAS – 24 with 1° OCD and 30 with 1° tic disorder.  Mean age of 8.94, mean age at onset of symptoms was 7.84, and mean duration of symptoms was 1.43 years.
  2. 157 first-degree relatives were evaluated – 100 parents (53♀ & 47♂), with a mean age of 40.72, and 57 siblings (33♂ & 24♀), with a mean age of 9.37, were evaluated for tic disorders.
  3. 139 first degree relatives were evaluated – 100 parents and 39 sibling’s ≥ 6 years of age (2° to DICA-P) were evaluated with clinical and structural psychiatric interviews for OCD, subclinical OCD, and other Axis I d/o.


  1. Method
  2. To determine the presence of lifetime mental illness in the first-degree relatives of the probands, a milieu of techniques was incorporated:  1.  structural and clinical interviews, 2.  self-report questionnaires, and 3.  observation/examination (especially for tics).
  3. All interviews were scored blindly in combination with interviews obtained from parents of 30 probands with Sydenham’s Chorea.
  4.                                                               Observed tics during the interviews were used as supplemental information only when confirmed by an independent examiner.
  5. A consensus of three mental health professionals, blind to proband         diagnosis, provided the best estimate of lifetime diagnosis of OCD, subclinical OCD, and OCPD.  Furthermore, a pediatric neurologist blind to both the proband and first-degree relative diagnoses confirmed their validity.
  6. Many of the siblings evaluated had not been observed after they passed through their complete risk period of OCD and tic d/o’s; therefore, a survival analysis was used to estimate their lifetime risk.
  7. OCD and OC Personality Disorder were diagnosed using DSM-IV criteria
  8. NIMH Global OCD Scale was employed for Subclinical OCD diagnosis.
  9. DSM-III-R and DSM-IV criteria were used to diagnose Tourette’s d/o (TD), chronic motor (CMTD) or chronic vocal tic d/o (CVTD), transient tic d/o (TTD), and tic d/o NOS (TDNOS); with the tics being present for a minimum of 4 weeks.


  1. Results
  2. 15% (n=15) of the parents met the diagnostic criteria for OCD.
  3.                                                               However, only 2 siblings met the OCD criteria; thus, this is too small of a number for age correlation measures.
  4. 15% (n=15) of the parents had a tic d/o.
  5.                                                               DSM-III-R criteria results – 4% (n=4) had TD, 2% (n=2) had CMTD, 1% (n=1) had CVTD, 1% (n=1) had TTD, and 7% (n=7) had TDNOS.
  6.                                                             DSM-IV criteria results – 1% (n=1) had TD, 14% (n=14) had TDNOS, and 0% for the remaining tic d/o’s.
  7. 25% (n=14) of siblings had tic d/o’s, with a 0.19 age-correlated risk.
  8. 26% (n=14) of the probands had a first degree relative with OCD; whereas, 39% (n=21) of the probands had a first degree relative with a motor or vocal tic d/o.
  9. Of the 24 probands with OCD, 9 of their relatives had OCD and 10 of their relatives had a tic d/o.
  10. Of the 30 probands with a tic d/o, 9 of their relatives had OCD and 14 relatives had a tic d/o.
  11. Of the 54 probands in the study; 37% (n=20) had ≥1 family member with a tic d/o, and 46% (n=25) had ≥1 family member diagnosed with OCD or Subclinical OCD.
  12. Hence, 36/54 (67%) had at least one family member with a diagnosis of OCD, Subclinical OCD, OCPD, and/or a tic d/o.
  13. Of interest however:  40% (n=40) of the parents had been or where diagnosed with a Major Depressive Episode (MDE); while, 8% (n=4) of the siblings had been or where diagnosed with MDE.


  1. Strength & Weaknesses
  2. Strengths:
  3.                                                               Large number of first-degree relatives with a high percentage of in-person interviews.  In addition, multiple sources of data where collected, and the final diagnoses where via blinded consensus.
  4. Weaknesses:
  5. The young age of the siblings, because many had not passed through the age of risk for OCD and tic d/o’s.  Thus, the number of affected siblings may be underestimated
  6. There was no control group of normal probands (+) or probands with other diagnoses (-).

iii.                Interviewers of family members were not blind to the goal of the study or to the probable diagnoses of OCD, tic d/o, or Sydenham Chorea for the probands.


VII.          Conclusion

  1. When comparing the results of the study to those found in the general population for first degree relatives of non-selected groups of children with OCD and/or a tic d/o, it can be inferred that the rates of OCD and tic d/o in the first degree relatives of patients with PANDAS is similar.
  2.                                                               17-20% Parents of children diagnosed with childhood-onset OCD have been found to have OCD, and 16% of this parent population was found to have tics.
  3.                                                             First-degree relatives of patients with childhood and adolescent onset of a tic d/o demonstrate a 23% rate of OCD, 13.6% rate of TD, and a 7.8% rate of chronic tic d/o.

                                                          iii.      A 16% rate of OCD and a 17.6% rate of tic d/o’s have been associated with family members of patient’s with TD.


VIII.       Treatment Recommendations

  1. Diagnostic Tests:
  2. Any child with an abrupt onset or exacerbation of OCD and/or tic d/o should have a throat culture obtained, especially if their past medical history is positive for PANDAS.  If (+), then it should be appropriately treated with antibiotics.
  3. If the OCD and/or tic d/o symptoms have been present for greater than one week, it is also adventitious to have serial antistreptococcal immunoglobulin titers obtained.  This will allow the physician to document a preceding GABHS or other Streptococcus sp.  infection.  If the child has PANDAS, a rise in the titer will appear between 4-6 weeks following the infections; titers should be coordinated to catch this rise.
  4. Pharmacological Intervention:
  5.                                                               Any child with a positive throat culture for Streptococcus Sp., regardless if PANDAS symptoms are present, should be administered antibiotics (General population carrier rate for Streptococcus sp. is only 5-10%)..
  6.                                                             Current research had demonstrated the prophylaxis of children in the PANDAS subgroup, with either penicillin or azithromycin, is effective in decreasing streptococcal infections and exacerbation of their neuropsyciatric symptoms.
  7. Neuropsychiatric Symptom Treatment:
  8.                                                               OCD – Typically treated with an SSRI (i.e. Paxil, Prosac, Zoloft, and Lexapro) in addition to cognitive behavioral therapy.
  9.                                                             Tic d/o’s – treatment is based on the specific symptoms and there is an array of pharmacologic agents that can be utilized.
  10. Immunomodulatory Treatment:
  11.                                                               This treatment is slightly more invasive, expensive, and involves the administration of IV Immunoglobulin and therapeutic plasma exchange.  Although invasive, research has demonstrated that this treatment can result in significant and persistent improvement in those children that are severely affected by PANDAS.  This option, because of its cost and invasiveness, is considered a second-line treatment option.




  1. Garvey MA, Perlmutter SJ, Allen AJ, et al. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry. 1999;45:1564-1571
  2. Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. Pediatrics. 2004;113:883-886
  3. Lougee L. Perlmutter SJ. Nicolson R. Garvey MA. Swedo SE.  Psychiatric disorders in first-degree relatives of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).  Journal of the American Academy of Child & Adolescent Psychiatry. 39(9):1120-6, 2000 Sep
  4. Snider LA. Lougee L. Slattery M. Grant P. Swedo SE.  Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders.  Biological Psychiatry. 57(7):788-92, 2005 Apr 1
  5. Swedo SE. Leonard HL. Rapoport JL.  The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction.  Pediatrics. 113(4):907-11, 2004 Apr
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