2020
Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron types
2017
Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum
Frick L, Rapanelli M, Jindachomthong K, Grant P, Leckman JF, Swedo S, Williams K, Pittenger C. Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum. Brain Behavior And Immunity 2017, 69: 304-311. PMID: 29233751, PMCID: PMC5857467, DOI: 10.1016/j.bbi.2017.12.004.Peer-Reviewed Original ResearchConceptsGroup A beta-hemolytic streptococciCholinergic interneuronsPediatric Autoimmune Neuropsychiatric Disorder AssociatedNeuropsychiatric Disorder AssociatedStriatal cholinergic interneuronsStriatum of miceBeta-hemolytic streptococciBrain antigensPANDAS patientsIntravenous immunoglobulinStriatal interneuronsNeuropsychiatric symptomsObsessive-compulsive disorderSymptom improvementGABAergic interneuronsClinical trialsHealthy controlsDisorders AssociatedTic disordersChildhood onsetInterneuronsLocus of pathologyElevated bindingAntibodiesStriatumA total-population multigenerational family clustering study of autoimmune diseases in obsessive–compulsive disorder and Tourette’s/chronic tic disorders
Mataix-Cols D, Frans E, Pérez-Vigil A, Kuja-Halkola R, Gromark C, Isomura K, Fernández de la Cruz L, Serlachius E, Leckman JF, Crowley JJ, Rück C, Almqvist C, Lichtenstein P, Larsson H. A total-population multigenerational family clustering study of autoimmune diseases in obsessive–compulsive disorder and Tourette’s/chronic tic disorders. Molecular Psychiatry 2017, 23: 1652-1658. PMID: 29133949, PMCID: PMC5951741, DOI: 10.1038/mp.2017.215.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderAutoimmune diseasesChronic tic disorderIndividual autoimmune diseasesThird-degree relativesTic disordersRisk of ADsNational Patient RegisterPatterns of comorbidityFirst-degree relativesPatient RegisterPlacental transmissionNationwide studyBirth cohortCTD casesFamilial clusteringDisordersComorbiditiesPopulation controlsProbandsOCD probandsBiological relativesDiseaseFamilial linkRiskLongitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS)
Leon J, Hommer R, Grant P, Farmer C, D’Souza P, Kessler R, Williams K, Leckman JF, Swedo S. Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). European Child & Adolescent Psychiatry 2017, 27: 637-643. PMID: 29119300, DOI: 10.1007/s00787-017-1077-9.Peer-Reviewed Original ResearchConceptsPediatric autoimmune neuropsychiatric disordersAutoimmune neuropsychiatric disordersIntravenous immunoglobulinStreptococcal infectionDose of IVIGNeuropsychiatric disordersPlacebo-controlled trialSignificant obsessive-compulsive symptomsPopulation of childrenCognitive behavioral therapySubacute illnessSydenham's choreaBlinded infusionChronic coursePsychiatric medicationsTreatment modalitiesSpecific symptomsChildhood-onset OCDLongitudinal courseNatural historyObsessive-compulsive symptomsBehavioral therapyExacerbationParents of participantsTelephone interviewsClinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I—Psychiatric and Behavioral Interventions
Thienemann M, Murphy T, Leckman J, Shaw R, Williams K, Kapphahn C, Frankovich J, Geller D, Bernstein G, Chang K, Elia J, Swedo S. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I—Psychiatric and Behavioral Interventions. Journal Of Child And Adolescent Psychopharmacology 2017, 27: 566-573. PMID: 28722481, PMCID: PMC5610394, DOI: 10.1089/cap.2016.0145.Peer-Reviewed Original ResearchConceptsPediatric acute-onset neuropsychiatric syndromeNeuropsychiatric syndromeInitial treatment doseEvidence-based interventionsPANDAS patientsImmunomodulatory therapyStreptococcal infectionChronic stageSymptomatic treatmentPsychopharmacologic interventionsPsychopharmacologic treatmentSymptom improvementSyndrome AssociatedConsensus guidelinesPsychotropic medicationsClinical managementInflammatory processCurrent guidelinesGuideline SeriesTreatment doseClinical experienceBehavioral symptomsVaried symptomsTherapeutic interventionsBehavioral interventions
2016
Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections
Williams KA, Swedo SE, Farmer CA, Grantz H, Grant PJ, D’Souza P, Hommer R, Katsovich L, King RA, Leckman JF. Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections. Journal Of The American Academy Of Child & Adolescent Psychiatry 2016, 55: 860-867.e2. PMID: 27663941, DOI: 10.1016/j.jaac.2016.06.017.Peer-Reviewed Original ResearchConceptsPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulinAutoimmune neuropsychiatric disordersYale-Brown Obsessive Compulsive ScaleChildren's Yale-Brown Obsessive Compulsive ScaleStreptococcal infectionIVIG groupPlacebo groupObsessive-compulsive disorderClinical Global Impression improvement ratingNeuropsychiatric disordersDouble-blind infusionDouble-blind phaseSustained symptom improvementDouble-blind comparisonOpen-label treatmentPrimary outcome measureSevere obsessive-compulsive disorderCY-BOCS total scoreCross-reactive antibodiesIdentification of biomarkersCY-BOCS scoresObsessive Compulsive ScaleImmunomodulatory therapyControlled Trials
2015
Maternal History of Autoimmune Disease and Later Development of Tourette Syndrome in Offspring
Dalsgaard S, Waltoft BL, Leckman JF, Mortensen PB. Maternal History of Autoimmune Disease and Later Development of Tourette Syndrome in Offspring. Journal Of The American Academy Of Child & Adolescent Psychiatry 2015, 54: 495-501.e1. PMID: 26004665, DOI: 10.1016/j.jaac.2015.03.008.Peer-Reviewed Original ResearchConceptsAdjusted incidence rate ratioIncidence rate ratiosMaternal autoimmune diseaseRisk of TSAutoimmune diseasesTourette syndromeMaternal historyNational Danish health registersNationwide prospective cohort studyDanish health registersPrior autoimmune diseaseProspective cohort studyParental psychiatric diagnosisDiagnosis of TSCohort studyHealth registersPerson yearsPrior diagnosisNeuroimmunological disordersIncidence rateTS diagnosisPsychiatric diagnosisPossible associationPoisson regressionPaternal age
2014
Disordered Eating and Food Restrictions in Children with PANDAS/PANS
Toufexis MD, Hommer R, Gerardi DM, Grant P, Rothschild L, D'Souza P, Williams K, Leckman J, Swedo SE, Murphy TK. Disordered Eating and Food Restrictions in Children with PANDAS/PANS. Journal Of Child And Adolescent Psychopharmacology 2014, 25: 48-56. PMID: 25329522, PMCID: PMC4340640, DOI: 10.1089/cap.2014.0063.Peer-Reviewed Original ResearchConceptsPediatric acute-onset neuropsychiatric syndromeClinical presentationRestrictive food intake disorderFood intake disorderFear of chokingSymptom onsetMale predominanceNeuropsychiatric symptomsNeuropsychiatric syndromeSudden onsetFood intakeFood refusalDiagnostic criteriaFood restrictionMental disordersYounger ageBody image distortionStreptococcal bacteriaStatistical ManualSymptomsTreatment implicationsDisordersPresentationSensory issuesChildrenPediatric Acute-Onset Neuropsychiatric Syndrome
Murphy TK, Gerardi DM, Leckman JF. Pediatric Acute-Onset Neuropsychiatric Syndrome. Psychiatric Clinics Of North America 2014, 37: 353-374. PMID: 25150567, DOI: 10.1016/j.psc.2014.06.001.Peer-Reviewed Original ResearchConceptsPediatric acute-onset neuropsychiatric syndromeNeuropsychiatric syndromePediatric autoimmune neuropsychiatric disordersAutoimmune neuropsychiatric disordersAutoimmune processClinical presentationObsessive-compulsive disorderNeuropsychiatric disordersSyndromeDisordersChildrenPathophysiologySymptoms
2011
Involvement of immunologic and biochemical mechanisms in the pathogenesis of Tourette’s syndrome
Landau YE, Steinberg T, Richmand B, Leckman JF, Apter A. Involvement of immunologic and biochemical mechanisms in the pathogenesis of Tourette’s syndrome. Journal Of Neural Transmission 2011, 119: 621-626. PMID: 22139323, PMCID: PMC3936959, DOI: 10.1007/s00702-011-0739-x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAutoimmune DiseasesBrain ChemistryChildComorbidityFemaleHumansMaleOxidative StressProspective StudiesTourette SyndromeConceptsTourette syndrome groupTourette syndromeSyndrome groupHealthy age-matched control subjectsTertiary pediatric medical centerAge-matched control subjectsIgG-4 levelsPediatric medical centerNovel therapeutic modalitiesNon-ceruloplasmin copperQuantitative immunoglobulinsImmunological markersControl subjectsHealthy childrenMedical recordsPhonic ticsMedical CenterTherapeutic modalitiesControl groupBiochemical markersSyndromeDemographic dataBiochemical indicesOxidative stressNeurodevelopmental disorders
2002
Obsessive-compulsive disorders in children. Subtypes of OCD and their relation to infection with group A streptococci.
Thomsen PH, Leckman J. Obsessive-compulsive disorders in children. Subtypes of OCD and their relation to infection with group A streptococci. Ugeskrift For Laeger 2002, 164: 3763-7. PMID: 12362609.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderSubtype of OCDBeta-haemolytic streptococciBody dysmorphic disorderAdult onsetSudden onsetNeurological abnormalitiesClinical consequencesPenicillin treatmentTourette syndromeSpecific subtypesObsessive-compulsive symptomsSuch disordersSubtypesDysmorphic disorderDisordersSyndromeInfectionDevelopmental disordersMore boysPresent reviewOnsetStreptococciRemissionRelapse