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
A 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 linkRiskRare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome
Huang AY, Yu D, Davis LK, Sul JH, Tsetsos F, Ramensky V, Zelaya I, Ramos EM, Osiecki L, Chen JA, McGrath LM, Illmann C, Sandor P, Barr CL, Grados M, Singer HS, Nöthen MM, Hebebrand J, King RA, Dion Y, Rouleau G, Budman CL, Depienne C, Worbe Y, Hartmann A, Müller-Vahl KR, Stuhrmann M, Aschauer H, Stamenkovic M, Schloegelhofer M, Konstantinidis A, Lyon GJ, McMahon WM, Barta C, Tarnok Z, Nagy P, Batterson JR, Rizzo R, Cath DC, Wolanczyk T, Berlin C, Malaty IA, Okun MS, Woods DW, Rees E, Pato CN, Pato MT, Knowles JA, Posthuma D, Pauls DL, Cox NJ, Neale BM, Freimer NB, Paschou P, Mathews CA, Scharf JM, Coppola G, Genetics T, Bruun R, Chouinard S, Darrow S, Greenberg E, Hirschtritt M, de la Tourette Syndrome GWAS Replication Initiative T, Kurlan R, Leckman J, Robertson M, Smit J. Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome. Neuron 2017, 94: 1101-1111.e7. PMID: 28641109, PMCID: PMC5568251, DOI: 10.1016/j.neuron.2017.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultCalcium-Binding ProteinsCase-Control StudiesCell Adhesion Molecules, NeuronalChildContactinsDNA Copy Number VariationsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleNerve Tissue ProteinsNeural Cell Adhesion MoleculesOdds RatioTourette SyndromeWhite PeopleYoung AdultConceptsCopy number variantsRare copy number variantsSignificant lociGenome-wide significant lociWide significant lociRare structural variationAncestry-matched controlsSNP microarray dataGlobal CNV burdenEuropean ancestry samplesGenetic architectureUnderlying genetic causeMicroarray dataNumber variantsTS casesCNV burdenSingleton eventsGenetic causeStructural variationsLociPathogenic copy number variantsAbnormal developmentModel neuropsychiatric disorderTS riskVariants
2015
Obsessive–compulsive symptoms are associated with psychiatric comorbidities, behavioral and clinical problems: a population-based study of Brazilian school children
Alvarenga PG, do Rosario MC, Cesar RC, Manfro GG, Moriyama TS, Bloch MH, Shavitt RG, Hoexter MQ, Coughlin CG, Leckman JF, Miguel EC. Obsessive–compulsive symptoms are associated with psychiatric comorbidities, behavioral and clinical problems: a population-based study of Brazilian school children. European Child & Adolescent Psychiatry 2015, 25: 175-182. PMID: 26015374, DOI: 10.1007/s00787-015-0723-3.Peer-Reviewed Original ResearchConceptsFamily History ScreenObsessive-compulsive disorderObsessive-compulsive symptomsSchool-aged childrenChild Behavior ChecklistUnaffected controlsPediatric-onset obsessive-compulsive disorderPresence of OCSPopulation-based studyComorbid psychiatric disordersMajor depressive disorderWell-Being AssessmentOCD groupBrazilian school childrenGroup of childrenPsychiatric comorbidityDepressive disorderClinical impactFunctional impairmentPsychiatric disordersClinical problemOCS groupDiagnostic groupsSignificant socio-demographic differencesSocio-demographic differencesMortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study
Dalsgaard S, Østergaard SD, Leckman JF, Mortensen PB, Pedersen MG. Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study. The Lancet 2015, 385: 2190-2196. PMID: 25726514, DOI: 10.1016/s0140-6736(14)61684-6.Peer-Reviewed Original ResearchMeSH KeywordsAccidentsAdolescentAdultAge of OnsetAttention Deficit and Disruptive Behavior DisordersAttention Deficit Disorder with HyperactivityCase-Control StudiesCause of DeathChildChild, PreschoolConduct DisorderCross-Sectional StudiesDenmarkFemaleHumansInfantMalePoisson DistributionRisk FactorsSubstance-Related DisordersYoung AdultConceptsMortality rate ratiosAttention deficit hyperactivity disorderHighest mortality rate ratiosSubstance use disordersOppositional defiant disorderDeficit hyperactivity disorderExcess mortalityConduct disorderUse disordersMortality rateDefiant disorderHyperactivity disorderNationwide cohort studyDanish national registersCommon mental disordersExclusion of individualsCohort studyLundbeck FoundationCommon causeFamily historyCohort membersLarge cohortPsychiatric disordersUnnatural causesDanish individuals
2013
Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: Initial findings
Zebardast N, Crowley MJ, Bloch MH, Mayes LC, Vander Wyk BV, Leckman JF, Pelphrey KA, Swain JE. Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: Initial findings. Psychiatry Research 2013, 214: 33-41. PMID: 23916249, PMCID: PMC3932431, DOI: 10.1016/j.pscychresns.2013.05.009.Peer-Reviewed Original ResearchConceptsTourette syndromeFunctional magnetic resonance imagingHealthy subjectsTic severityWhole-brain functional magnetic resonance imagingYale Global Tic Severity ScaleTactile startle responseCase-control study designTic Severity ScaleCortical-striatal circuitsBrain activityMagnetic resonance imagingMultiple brain regionsLeft middle frontal gyrusMiddle frontal gyrusDegree of PPIPulse-alone stimuliBlock-design fMRI paradigmTic symptomsNeuropathological dataHealthy controlsPrepulse inhibitionDevelopmental neuropsychiatric disordersSensorimotor gatingLeft caudate
2012
Genome-wide association study of Tourette's syndrome
Scharf JM, Yu D, Mathews CA, Neale BM, Stewart SE, Fagerness JA, Evans P, Gamazon E, Edlund CK, Service SK, Tikhomirov A, Osiecki L, Illmann C, Pluzhnikov A, Konkashbaev A, Davis LK, Han B, Crane J, Moorjani P, Crenshaw AT, Parkin MA, Reus VI, Lowe TL, Rangel-Lugo M, Chouinard S, Dion Y, Girard S, Cath DC, Smit JH, King RA, Fernandez TV, Leckman JF, Kidd KK, Kidd JR, Pakstis AJ, State MW, Herrera LD, Romero R, Fournier E, Sandor P, Barr CL, Phan N, Gross-Tsur V, Benarroch F, Pollak Y, Budman CL, Bruun RD, Erenberg G, Naarden AL, Lee PC, Weiss N, Kremeyer B, Berrío GB, Campbell DD, Cardona Silgado JC, Ochoa WC, Mesa Restrepo SC, Muller H, Valencia Duarte AV, Lyon GJ, Leppert M, Morgan J, Weiss R, Grados MA, Anderson K, Davarya S, Singer H, Walkup J, Jankovic J, Tischfield JA, Heiman GA, Gilbert DL, Hoekstra PJ, Robertson MM, Kurlan R, Liu C, Gibbs JR, Singleton A, Hardy J, Strengman E, Ophoff R, Wagner M, Moessner R, Mirel D, Posthuma D, Sabatti C, Eskin E, Conti D, Knowles J, Ruiz-Linares A, Rouleau G, Purcell S, Heutink P, Oostra B, McMahon W, Freimer N, Cox N, Pauls D. Genome-wide association study of Tourette's syndrome. Molecular Psychiatry 2012, 18: 721-728. PMID: 22889924, PMCID: PMC3605224, DOI: 10.1038/mp.2012.69.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAttention Deficit Disorder with HyperactivityCase-Control StudiesChromosomes, Human, Pair 9FemaleFibrillar CollagensGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansInternational CooperationMaleMeta-Analysis as TopicObsessive-Compulsive DisorderPolymorphism, Single NucleotideTourette SyndromeWhite PeopleYoung AdultConceptsGenome-wide association studiesFirst genome-wide association studyAssociation studiesTop signalsFull genetic architectureAncestry-matched controlsEuropean ancestry samplesGenetic architectureGWAS dataComplex inheritanceEuropean-derived populationsSusceptibility variantsSusceptibility genesEventual identificationEuropean ancestryCosta RicaChromosome 9q32Familial recurrence rateNorth AmericaComplete understandingAmerican populationCentral ValleyNeuropsychiatric diseasesDevelopmental disordersGenes
2011
Rare Copy Number Variants in Tourette Syndrome Disrupt Genes in Histaminergic Pathways and Overlap with Autism
Fernandez TV, Sanders SJ, Yurkiewicz IR, Ercan-Sencicek AG, Kim YS, Fishman DO, Raubeson MJ, Song Y, Yasuno K, Ho WS, Bilguvar K, Glessner J, Chu SH, Leckman JF, King RA, Gilbert DL, Heiman GA, Tischfield JA, Hoekstra PJ, Devlin B, Hakonarson H, Mane SM, Günel M, State MW. Rare Copy Number Variants in Tourette Syndrome Disrupt Genes in Histaminergic Pathways and Overlap with Autism. Biological Psychiatry 2011, 71: 392-402. PMID: 22169095, PMCID: PMC3282144, DOI: 10.1016/j.biopsych.2011.09.034.Peer-Reviewed Original ResearchConceptsCopy number variationsRare copy number variationsNovel risk regionsEnrichment of genesGamma-aminobutyric acid receptor genesNervous system developmentEtiology of TSParent-child triosRare copy number variantsCopy number variantsGene mappingPathway analysisDe novo eventsAxon guidanceCell adhesionMolecular pathwaysNumber variationsRelevant pathwaysCNV analysisNumber variantsGenesReceptor geneDe novoNovo eventsPathwayThe familial association of tourette's disorder and ADHD: The impact of OCD symptoms
O'Rourke JA, Scharf JM, Platko J, Stewart SE, Illmann C, Geller DA, King RA, Leckman JF, Pauls DL. The familial association of tourette's disorder and ADHD: The impact of OCD symptoms. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2011, 156: 553-560. PMID: 21557467, PMCID: PMC3292860, DOI: 10.1002/ajmg.b.31195.Peer-Reviewed Original Research
2010
Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study
Leckman JF, King RA, Gilbert DL, Coffey BJ, Singer HS, Dure LS, Grantz H, Katsovich L, Lin H, Lombroso PJ, Kawikova I, Johnson DR, Kurlan RM, Kaplan EL. Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study. Journal Of The American Academy Of Child & Adolescent Psychiatry 2010, 50: 108-118.e3. PMID: 21241948, PMCID: PMC3024577, DOI: 10.1016/j.jaac.2010.10.011.Peer-Reviewed Original ResearchConceptsExacerbation of ticsGABHS infectionStreptococcal infectionSymptom exacerbationStreptococcal upper respiratory tract infectionPediatric autoimmune neuropsychiatric disordersUpper respiratory tract infectionObsessive-compulsive symptomsAutoimmune neuropsychiatric disordersHemolytic streptococcal infectionRespiratory tract infectionsThroat swab cultureLongitudinal studyProspective longitudinal studyPANDAS subjectsClinical exacerbationStreptococcal antibodiesTract infectionsClinical symptomsGABHS infectionsGroup of childrenLaboratory valuesSwab culturesClinical conditionsClinical evaluatorsPsychosocial outcome and psychiatric comorbidity in older adolescents with Tourette syndrome: controlled study
Gorman DA, Thompson N, Plessen KJ, Robertson MM, Leckman JF, Peterson BS. Psychosocial outcome and psychiatric comorbidity in older adolescents with Tourette syndrome: controlled study. The British Journal Of Psychiatry 2010, 197: 36-44. PMID: 20592431, PMCID: PMC2894981, DOI: 10.1192/bjp.bp.109.071050.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderGlobal Assessment Scale scoresTourette syndromePsychosocial outcomesComorbidity ratesChildren's Global Assessment Scale scoresPsychosocial functioningImprovement of ticsLifetime psychiatric disordersLower Children's Global Assessment Scale (CGAS) scoresAssessment Scale scoresAge 18 yearsYears of ageHigh comorbidity ratesOlder adolescentsLifetime comorbidity ratesLower CGAS scoresPoor psychosocial outcomesComorbidity outcomesPsychiatric comorbidityMajor depressionCGAS scoresPsychiatric disordersTic severityObsessive-compulsive disorder symptomsThe Human Immune Response to Streptococcal Extracellular Antigens: Clinical, Diagnostic, and Potential Pathogenetic Implications
Johnson DR, Kurlan R, Leckman J, Kaplan EL. The Human Immune Response to Streptococcal Extracellular Antigens: Clinical, Diagnostic, and Potential Pathogenetic Implications. Clinical Infectious Diseases 2010, 50: 481-490. PMID: 20067422, DOI: 10.1086/650167.Peer-Reviewed Original ResearchConceptsAntibody titersImmune responseSingle antibody titerStreptococcal extracellular antigensB antibody titersHuman antibody responseHuman immune responsePaediatric study participantsSymptoms of infectionPotential pathogenetic implicationsThroat culturesGAS infectionAntibody responseSubsequent sequelaePathogenetic mechanismsImmunologic confirmationBlood samplesEpidemiological studiesPathogenetic implicationsStreptococcus antigensCulture resultsStudy participantsImportant human pathogenInfectionExtracellular antigens
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 diseasesInfectionDiagnosisAssociation of the serotonin transporter polymorphism and obsessive‐compulsive disorder: Systematic review
Bloch MH, Landeros‐Weisenberger A, Sen S, Dombrowski P, Kelmendi B, Coric V, Pittenger C, Leckman JF. Association of the serotonin transporter polymorphism and obsessive‐compulsive disorder: Systematic review. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2008, 147B: 850-858. PMID: 18186076, DOI: 10.1002/ajmg.b.30699.Peer-Reviewed Original Research
2006
A Controlled Family Study of Attention-Deficit/Hyperactivity Disorder and Tourette's Disorder
STEWART SE, ILLMANN C, GELLER DA, LECKMAN JF, KING R, PAULS DL. A Controlled Family Study of Attention-Deficit/Hyperactivity Disorder and Tourette's Disorder. Journal Of The American Academy Of Child & Adolescent Psychiatry 2006, 45: 1354-1362. PMID: 17075358, DOI: 10.1097/01.chi.0000251211.36868.fe.Peer-Reviewed Original Research
2005
Increased serum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette’s syndrome
Leckman JF, Katsovich L, Kawikova I, Lin H, Zhang H, Krönig H, Morshed S, Parveen S, Grantz H, Lombroso PJ, King RA. Increased serum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette’s syndrome. Biological Psychiatry 2005, 57: 667-673. PMID: 15780855, DOI: 10.1016/j.biopsych.2004.12.004.Peer-Reviewed Original ResearchConceptsEarly-onset obsessive-compulsive disorderObsessive-compulsive disorderSymptom exacerbationInterleukin-12Control subjectsImmune responseTourette syndromeTumor necrosis factor-alpha concentrationsNecrosis factor-alpha concentrationsAge-matched control subjectsInvolvement of innateLocal cytokine synthesisT cell immunityHumoral immune responseCentral nervous systemInnate immune responseLongitudinal studyProspective longitudinal studyT cell activationCell immunitySerum levelsPediatric populationCommon infectionsSerum concentrationsInflammatory process
2004
Altered Interhemispheric Connectivity in Individuals With Tourettes Disorder
Plessen KJ, Wentzel-Larsen T, Hugdahl K, Feineigle P, Klein J, Staib LH, Leckman JF, Bansal R, Peterson BS. Altered Interhemispheric Connectivity in Individuals With Tourettes Disorder. American Journal Of Psychiatry 2004, 161: 2028-2037. PMID: 15514403, DOI: 10.1176/appi.ajp.161.11.2028.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAttention Deficit Disorder with HyperactivityCase-Control StudiesCerebral CortexComorbidityCorpus CallosumCross-Sectional StudiesFunctional LateralityHumansMagnetic Resonance ImagingMaleNeuronal PlasticityObsessive-Compulsive DisorderPrefrontal CortexSeverity of Illness IndexTourette SyndromeConceptsCorpus callosum sizeCallosum sizeTourette's disorderCorpus callosumCerebral hemispheresComparison subjectsCross-sectional case-control studyMidsagittal corpus callosum areaCorpus callosum areaCase-control studyEffects of medicationAge 30 yearsCortical inhibitory interneuronsHigh-resolution magnetic resonanceHealthy comparison subjectsMajor commissureComorbid illnessesTic symptomsOrbitofrontal cortical volumeCortical volumeInhibitory interneuronsInterhemispheric connectivityInhibitory inputsTic severityPrior evidence
2003
Disruptive Behavior in Children With Tourette's Syndrome: Association With ADHD Comorbidity, Tic Severity, and Functional Impairment
SUKHODOLSKY DG, SCAHILL L, ZHANG H, PETERSON BS, KING RA, LOMBROSO PJ, KATSOVICH L, FINDLEY D, LECKMAN JF. Disruptive Behavior in Children With Tourette's Syndrome: Association With ADHD Comorbidity, Tic Severity, and Functional Impairment. Journal Of The American Academy Of Child & Adolescent Psychiatry 2003, 42: 98-105. PMID: 12500082, DOI: 10.1097/00004583-200301000-00016.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderComorbid attention-deficit/hyperactivity disorderDisruptive behaviorFamily functioningParent ratingsTeacher ratingsDiagnosis of ADHDVineland Adaptive Behavior ScalesDisruptive behavior problemsHierarchical regression analysisAdaptive Behavior ScalesBest-estimate DSM-IV diagnosesUnaffected control childrenTourette syndromeConduct problemsDelinquency scoresHyperactivity disorderADHD comorbidityDelinquent behaviorBehavior problemsDSM-IV diagnosisDependent measuresDiagnostic statusBehavior ScaleFunctional impairment