2022
Mispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids
Brady M, Mariani J, Koca Y, Szekely A, King R, Bloch M, Landeros-Weisenberger A, Leckman J, Vaccarino F. Mispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids. Molecular Psychiatry 2022, 27: 5007-5019. PMID: 36447010, PMCID: PMC9949887, DOI: 10.1038/s41380-022-01880-5.Peer-Reviewed Original ResearchConceptsTourette syndromeInterneuron deficitsGABAergic interneuronsHealthy controlsNeurodevelopmental underpinningsNeuropathological deficitsBG circuitryNeuropsychiatric disordersDecreased differentiationT patientsInterneuronsAltered expressionPotential mechanismsCilia disruptionSonic hedgehogOrganoidsStem cellsTS individualsPluripotent stem cellsGli transcription factorsDeficitsOrganoid differentiationEarly stagesCholinergicPatientsA Functional Magnetic Resonance Imaging Study of Tic Suppression in Tourette Syndrome
Peterson B, Shudlarski P, Anderson A, Zhang H, Gatenby J, Lacadie C, Leckman J, Gore J. A Functional Magnetic Resonance Imaging Study of Tic Suppression in Tourette Syndrome. 2022, 198-205. DOI: 10.4324/9780203822937-19.Peer-Reviewed Original ResearchMRI signal changesFunctional MRI signal changesFunctional debilityTourette syndromeTic suppressionNeuropsychiatric disordersNormal brain processesMagnetic resonance imaging studyResonance imaging studyFunctional magnetic resonance imaging studySignal changesFrequent causeBlood flowNeuronal activityImaging studiesStatistical significanceSignificant increaseSyndromeBehavioral problemsDebilityDisordersFailed inhibitionBrain processesImpulse controlIndirect measure
2020
Empiric Recurrence Risk Estimates for Chronic Tic Disorders: Implications for Genetic Counseling
Heiman GA, Rispoli J, Seymour C, Leckman JF, King RA, Fernandez TV. Empiric Recurrence Risk Estimates for Chronic Tic Disorders: Implications for Genetic Counseling. Frontiers In Neurology 2020, 11: 770. PMID: 32849224, PMCID: PMC7432137, DOI: 10.3389/fneur.2020.00770.Peer-Reviewed Original ResearchChronic tic disorderRecurrence risk estimatesTic disordersRecurrence riskTourette's disorderRisk estimatesNeuropsychiatric disordersPopulation-based family studyGenetic counselingFirst-degree relativesQuality of lifeFamily studiesVocal ticsPopulation prevalenceFamilial recurrence riskSuch counselingGenetic testingDisordersRiskCounselingEmpiric recurrence riskGenetic variantsRange of risksHeterogeneous genetic architectureComorbiditiesAutoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections
Chain JL, Alvarez K, Mascaro-Blanco A, Reim S, Bentley R, Hommer R, Grant P, Leckman JF, Kawikova I, Williams K, Stoner JA, Swedo SE, Cunningham MW. Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections. Frontiers In Psychiatry 2020, 11: 564. PMID: 32670106, PMCID: PMC7328706, DOI: 10.3389/fpsyt.2020.00564.Peer-Reviewed Original ResearchPediatric autoimmune neuropsychiatric disordersAnti-neuronal autoantibodiesSerum autoantibody titersAutoimmune neuropsychiatric disordersSydenham's choreaAutoantibody titersEnzyme-linked immunosorbent assayCerebrospinal fluidNeuronal autoantigensNeuropsychiatric disordersPANDAS patientsPANDAS subjectsStreptococcal infectionHealthy controlsAcute symptomatic phaseBasal ganglia encephalitisGroup of autoantibodiesHealthy control subjectsCaMKII activationAttention deficit hyperactivity disorderHuman neuronal cellsDeficit hyperactivity disorderGroup of childrenAutoantibody biomarkersObsessive-compulsive disorderPathways to Wellbeing and a More Peaceful and Sustainable World: The Transformative Power of Children and Families
LECKMAN J, DONALDSON C, AFFOLTER F, PONGUTA L. Pathways to Wellbeing and a More Peaceful and Sustainable World: The Transformative Power of Children and Families. 児童青年精神医学とその近接領域 2020, 60: 278-298. DOI: 10.20615/jscap.60.3_278.Peer-Reviewed Original ResearchEarly childhood developmentECD servicesNeuropsychiatric disordersMulti-sectorial approachPhysical health
2019
What does immunology have to do with brain development and neuropsychiatric disorders?
Leckman J, Alvarenga P, Ravagnani B, Johnson I. What does immunology have to do with brain development and neuropsychiatric disorders? Revista De Medicina 2019, 98: 241-253. DOI: 10.11606/issn.1679-9836.v98i4p241-253.Peer-Reviewed Original ResearchImmune systemNormal brain developmentBrain developmentNeuropsychiatric disordersNeural circuitsGut-brain axisRelevant review articlesAutism spectrum disorderObsessive-compulsive disorderBody of evidenceImmune cellsMood disordersValid biomarkersSubset of individualsTourette syndromeNovel interventionsNeurodegenerative disordersPersonalized approachLiterature searchDisordersMultiple biological systemsPathobiologyNeural developmentTraditional literature searchIndividual microbiomes
2017
Longitudinal 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 interviewsGilles de la Tourette syndrome
Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, Roessner V, Woods DW, Hariz M, Mathews CA, Črnčec R, Leckman JF. Gilles de la Tourette syndrome. Nature Reviews Disease Primers 2017, 3: 16097. PMID: 28150698, DOI: 10.1038/nrdp.2016.97.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderFunctional brain anomaliesObsessive-compulsive disorderChildhood-onset neurodevelopmental disorderPathogenesis of GTSHyperactivity disorderMultiple common risk variantsNeurobiological dataConsiderable social stigmaNeural circuit levelTourette syndromeBehavioral methodsGilles deNeurodevelopmental disordersYears of ageFuture researchSocial stigmaBrain anomaliesPhonic ticsNeuropsychiatric disordersTargeted interventionsClinical phenotypeDisordersFunctional neurosurgeryDe novo mutationsTemporal Association of Certain Neuropsychiatric Disorders Following Vaccination of Children and Adolescents: A Pilot Case–Control Study
Leslie DL, Kobre RA, Richmand BJ, Guloksuz S, Leckman JF. Temporal Association of Certain Neuropsychiatric Disorders Following Vaccination of Children and Adolescents: A Pilot Case–Control Study. Frontiers In Psychiatry 2017, 8: 3. PMID: 28154539, PMCID: PMC5244035, DOI: 10.3389/fpsyt.2017.00003.Peer-Reviewed Original ResearchObsessive-compulsive disorderAnorexia nervosaNeuropsychiatric disordersPrior vaccinationPilot case-control studyAnxiety disordersConditional logistic regression modelsClear public health benefitsVaccination of childrenCase-control studyChronic tic disorderMajor depressive disorderChildhood infectious diseasesCertain neuropsychiatric disordersAttention deficit hyperactivity disorderPublic health benefitsLogistic regression modelsAntecedent administrationAntecedent infectionAntecedent vaccinationDeficit hyperactivity disorderInfluenza vaccinationVaccination scheduleIncident diagnosisCDC guidelines
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
2014
Editorial commentary: “What does immunology have to do with brain development and neuropsychiatric disorders?”
Leckman JF, Vaccarino FM. Editorial commentary: “What does immunology have to do with brain development and neuropsychiatric disorders?”. Brain Research 2014, 1617: 1-6. PMID: 25283746, DOI: 10.1016/j.brainres.2014.09.052.Commentaries, Editorials and LettersPediatric 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
2013
Brain Human Monoclonal Autoantibody from Sydenham Chorea Targets Dopaminergic Neurons in Transgenic Mice and Signals Dopamine D2 Receptor: Implications in Human Disease
Cox CJ, Sharma M, Leckman JF, Zuccolo J, Zuccolo A, Kovoor A, Swedo SE, Cunningham MW. Brain Human Monoclonal Autoantibody from Sydenham Chorea Targets Dopaminergic Neurons in Transgenic Mice and Signals Dopamine D2 Receptor: Implications in Human Disease. The Journal Of Immunology 2013, 191: 5524-5541. PMID: 24184556, PMCID: PMC3848617, DOI: 10.4049/jimmunol.1102592.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialAutoantibodiesBasal GangliaChildChoreaCross ReactionsDopamineDopaminergic NeuronsG(M1) GangliosideHEK293 CellsHumansImmunoglobulin GMiceMice, Inbred C57BLMice, TransgenicReceptors, Dopamine D2Recombinant Fusion ProteinsRheumatic FeverSignal TransductionStreptococcal InfectionsTransgenesConceptsSydenham's choreaDopamine D2 receptorsDopaminergic neuronsD2 receptorsTransgenic micePediatric autoimmune neuropsychiatric disordersDose-dependent inhibitoryMain neurologic manifestationsAutoimmune neuropsychiatric disordersBehavioral disordersHuman monoclonal autoantibodiesBrain AgsNeurologic manifestationsRheumatic feverChoreiform movementsTg miceBasal gangliaHuman dopamine D2 receptorAb reactivityTyrosine hydroxylaseAutoantibodiesB cellsMonoclonal autoantibodiesNeuropsychiatric disordersD2R
2012
Clinical assessment of Tourette syndrome and tic disorders
Cohen SC, Leckman JF, Bloch MH. Clinical assessment of Tourette syndrome and tic disorders. Neuroscience & Biobehavioral Reviews 2012, 37: 997-1007. PMID: 23206664, PMCID: PMC3674220, DOI: 10.1016/j.neubiorev.2012.11.013.Peer-Reviewed Original ResearchConceptsTourette syndromeAttention deficit hyperactivity disorderObsessive-compulsive disorderTreatment of TSImpaired sensorimotor gatingPercent of childrenImpulse control disordersDeficit hyperactivity disorderSomatic hypersensitivityTic symptomsPhonic ticsPurposeless movementsTic disordersClinical assessmentSensorimotor gatingControl disordersProper diagnosisMuscle groupsPremonitory urgesNeuropsychiatric disordersHyperactivity disorderDisordersAppropriate evaluationSyndromeSensory phenomenaBehavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders
Brimberg L, Benhar I, Mascaro-Blanco A, Alvarez K, Lotan D, Winter C, Klein J, Moses AE, Somnier FE, Leckman JF, Swedo SE, Cunningham MW, Joel D. Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders. Neuropsychopharmacology 2012, 37: 2076-2087. PMID: 22534626, PMCID: PMC3398718, DOI: 10.1038/npp.2012.56.Peer-Reviewed Original ResearchConceptsSydenham's choreaNeuropsychiatric disordersStreptococcal exposureImmunological abnormalitiesMotor symptomsRat modelAnimal modelsSelective serotonin reuptake inhibitor paroxetineGroup A streptococcal infectionsSerotonin reuptake inhibitor paroxetineSK-N-SH neuronal cellsMale Lewis ratsNovel rat modelNew animal modelCalcium/calmodulin-dependent protein kinase IIRelated neuropsychiatric disordersStreptococcal infectionLewis ratsAntibody depositionBasal gangliaCalmodulin-dependent protein kinase IIDopamine D1GAS antigensGlutamate levelsD2 receptors
2009
Clinical course of Tourette syndrome
Bloch MH, Leckman JF. Clinical course of Tourette syndrome. Journal Of Psychosomatic Research 2009, 67: 497-501. PMID: 19913654, PMCID: PMC3974606, DOI: 10.1016/j.jpsychores.2009.09.002.Peer-Reviewed Original ResearchConceptsTourette syndromeComorbid conditionsObsessive-compulsive disorderClinical courseLong-term clinical courseChildhood-onset neuropsychiatric disorderEarly adulthoodLong-term outcomesAttention deficit disorderTic symptomsDepressive disorderTic disordersVocal ticsGeneral populationNeuropsychiatric disordersLiterature searchRelevant articlesDisordersSyndromeChildrenAdulthood outcomesOne-thirdSymptomsTraditional literature searchThree-quarters
2008
Neuropsychiatric Disorders Associated With Streptococcal Infection: A Case-Control Study Among Privately Insured Children
Leslie DL, Kozma L, Martin A, Landeros A, Katsovich L, King RA, Leckman JF. Neuropsychiatric Disorders Associated With Streptococcal Infection: A Case-Control Study Among Privately Insured Children. Journal Of The American Academy Of Child & Adolescent Psychiatry 2008, 47: 1166-1172. PMID: 18724258, PMCID: PMC2783578, DOI: 10.1097/chi.0b013e3181825a3d.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAttention Deficit Disorder with HyperactivityCase-Control StudiesChildChild, PreschoolCross-Sectional StudiesDepressive Disorder, MajorFemaleHealth SurveysHumansIncidenceInsurance, HealthMaleMigraine DisordersNeurocognitive DisordersObsessive-Compulsive DisorderOdds RatioOtitis MediaRiskSinusitisStreptococcal InfectionsTic DisordersTourette SyndromeUnited StatesConceptsMajor depressive disorderAttention-deficit/hyperactivity disorderPrior streptococcal infectionStreptococcal infectionObsessive-compulsive disorderTic disordersTourette syndromeNeuropsychiatric disordersConditional logistic regression modelsStreptococcal sore throatDiagnosis of OCDCase-control studyLogistic regression modelsSore throatIncident diagnosisEpidemiologic evidenceDepressive disorderSubsequent diagnosisNoninfectious conditionsScarlet feverChildren ages 4Immune systemInfectious diseasesInfectionDiagnosis
2005
Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome
Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, Morgan TM, Mathews CA, Pauls DL, Rašin M, Gunel M, Davis NR, Ercan-Sencicek AG, Guez DH, Spertus JA, Leckman JF, Dure LS, Kurlan R, Singer HS, Gilbert DL, Farhi A, Louvi A, Lifton RP, Šestan N, State MW. Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome. Science 2005, 310: 317-320. PMID: 16224024, DOI: 10.1126/science.1116502.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdolescentAnimalsAttention Deficit Disorder with HyperactivityBrainChildChild, PreschoolChromosome InversionChromosome MappingChromosomes, Human, Pair 13DNADNA Mutational AnalysisFemaleFrameshift MutationHumansIn Situ Hybridization, FluorescenceMaleMembrane ProteinsMiceMutationNerve Tissue ProteinsPedigreeSequence Analysis, DNATourette SyndromeConceptsSequence variantsTourette syndromeChromosomal inversionsFrameshift mutantsCandidate genesExpression patternsControl chromosomesPrimary neuronal culturesFrameshift mutationSLITRK1Independent occurrenceMotor ticsDevelopmental neuropsychiatric disordersChronic vocalNeuronal culturesIdentical variantsUnrelated probandsBrain regionsNeuropsychiatric disordersSyndromeAntineural antibody in patients with Tourette’s syndrome and their family members
Yeh CB, Wu CH, Tsung HC, Chen CW, Shyu JF, Leckman JF. Antineural antibody in patients with Tourette’s syndrome and their family members. Journal Of Biomedical Science 2005, 13: 101-112. PMID: 16215701, DOI: 10.1007/s11373-005-9033-y.Peer-Reviewed Original ResearchConceptsAntineural antibodiesTourette syndromeTS patientsTic disordersControl groupFirst-degree family membersAge-matched control groupFamily membersSera of controlsImmunological pathophysiologyStreptococcal infectionPrimary cell culturesPatientsInfectious agentsSyndromeNeuropsychiatric disordersWestern blottingAntibodiesRat tissuesInteraction of geneticsGenetic vulnerabilitySerumDisordersFuture studiesCell cultures
2000
The Psychiatric Symptoms of Rheumatic Fever
Mercadante MT, Busatto GF, Lombroso PJ, Prado L, Rosário-Campos MC, do Valle R, Marques-Dias MJ, Kiss MH, Leckman JF, Miguel EC. The Psychiatric Symptoms of Rheumatic Fever. American Journal Of Psychiatry 2000, 157: 2036-2038. PMID: 11097972, DOI: 10.1176/appi.ajp.157.12.2036.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderRheumatic feverSydenham's choreaTic disordersHigh riskComparison groupFever groupMajor depressive disorderDeficit hyperactivity disorderObsessive-compulsive disorderDepressive disorderRisk factorsPsychiatric symptomsPsychiatric disordersChoreaFeverNeuropsychiatric disordersObsessive-compulsive symptomsRating ScaleHyperactivity disorderSymptomsDisordersADHD symptomsChildrenSemistructured interviews