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
2018
Chapter 49 Genetic susceptibility in obsessive-compulsive disorder
Fernandez TV, Leckman JF, Pittenger C. Chapter 49 Genetic susceptibility in obsessive-compulsive disorder. Handbook Of Clinical Neurology 2018, 148: 767-781. PMID: 29478613, DOI: 10.1016/b978-0-444-64076-5.00049-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsObsessive-compulsive disorderPotential novel therapeutic avenuesNovel therapeutic avenuesSpecific risk allelesUnderlying pathophysiologyLarge cohortLifelong disabilityImmune pathwaysTherapeutic avenuesNew treatmentsGenetic susceptibilityRisk allelesCandidate gene association studiesMouse knockout modelsGenetic findingsGene association studiesKnockout modelsOCD pathologyRisk variantsNotable inroadsGenetic variantsDisordersVulnerable pathwaysSubstantial genetic contributionRepetitive behaviors
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 bindingAntibodiesStriatumGilles 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 mutations
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 LettersFrom Attachment to Groups: Tapping Into the Neurobiology of Our Interconnectedness
Gordon I, Leckman JF, Berg DN. From Attachment to Groups: Tapping Into the Neurobiology of Our Interconnectedness. Journal Of The American Academy Of Child & Adolescent Psychiatry 2014, 53: 130-132. PMID: 24472246, DOI: 10.1016/j.jaac.2013.10.012.Peer-Reviewed Original Research
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 disordersD2RChapter Nine Neuroendocrine Aspects of Tourette Syndrome
Martino D, Macerollo A, Leckman JF. Chapter Nine Neuroendocrine Aspects of Tourette Syndrome. International Review Of Neurobiology 2013, 112: 239-279. PMID: 24295624, DOI: 10.1016/b978-0-12-411546-0.00009-3.Peer-Reviewed Original ResearchConceptsTourette syndromeObsessive-compulsive disorderStereotyped behaviorSubgroup of womenAction of testosteroneAnecdotal clinical evidenceDiurnal cortisol rhythmInjection of oxytocinStress steroid hormonesPreliminary evidenceAcute stress responseClinical evidenceAdrenal axisEstrogen levelsExogenous androgensGonadal hormonesCortisol rhythmNormal restorationAnimal modelsAndrogenic steroidsNeuroendocrine aspectsPatientsGender distributionBaseline activityNatural history
2012
Systematic review: Pharmacological treatment of tic disorders – Efficacy of antipsychotic and alpha-2 adrenergic agonist agents
Weisman H, Qureshi IA, Leckman JF, Scahill L, Bloch MH. Systematic review: Pharmacological treatment of tic disorders – Efficacy of antipsychotic and alpha-2 adrenergic agonist agents. Neuroscience & Biobehavioral Reviews 2012, 37: 1162-1171. PMID: 23099282, PMCID: PMC3674207, DOI: 10.1016/j.neubiorev.2012.09.008.Peer-Reviewed Original ResearchBehavioral, 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
2011
Variations in Maternal Behavior—Oxytocin and Reward Pathways—Peripheral Measures Matter?!
Leckman JF. Variations in Maternal Behavior—Oxytocin and Reward Pathways—Peripheral Measures Matter?! Neuropsychopharmacology 2011, 36: 2587-2588. PMID: 22071897, PMCID: PMC3230502, DOI: 10.1038/npp.2011.201.Peer-Reviewed Original ResearchOxytocin and social motivation
Gordon I, Martin C, Feldman R, Leckman JF. Oxytocin and social motivation. Developmental Cognitive Neuroscience 2011, 1: 471-493. PMID: 21984889, PMCID: PMC3185363, DOI: 10.1016/j.dcn.2011.07.007.Peer-Reviewed Original ResearchConceptsSocial motivationCourse of developmentBiobehavioral systemsRole of oxytocinSocial creaturesSocial partnersSensory inputKey unresolved questionGonadal axisGastrointestinal tractStress response axisMotivationOTR expressionOxytocinReceptor systemBrainSalienceReproductive organsResponse axisDetection pathwaySystem functionExternal environmentPeripheral componentsUnresolved questionsHumans
2010
Neurobiological Substrates of Tourette's Disorder
Leckman JF, Bloch MH, Smith ME, Larabi D, Hampson M. Neurobiological Substrates of Tourette's Disorder. Journal Of Child And Adolescent Psychopharmacology 2010, 20: 237-247. PMID: 20807062, PMCID: PMC2958453, DOI: 10.1089/cap.2009.0118.ChaptersThe 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. Journal Of Child And Adolescent Psychopharmacology 2010, 20: 317-331. PMID: 20807070, PMCID: PMC4003464, DOI: 10.1089/cap.2010.0043.Peer-Reviewed Original ResearchConceptsGroup A StreptococcusObsessive-compulsive disorderSydenham's choreaTourette's disorderRheumatic feverNeuropsychiatric symptomsPediatric Autoimmune Neuropsychiatric Disorder AssociatedPediatric autoimmune neuropsychiatric disordersA StreptococcusCommon anatomic areasNeuropsychiatric Disorder AssociatedAutoimmune neuropsychiatric disordersAttention-deficit/hyperactivity symptomsImmune dysfunctionUnknown etiologyBasal gangliaChildhood obsessive-compulsive disorderSudden onsetDisorders AssociatedMotor ticsVocal ticsTherapeutic aspectsThalamic sitesReference listsAnatomic areas
2009
Autism spectrum and obsessive–compulsive disorders: OC behaviors, phenotypes and genetics
Jacob S, Landeros‐Weisenberger A, Leckman JF. Autism spectrum and obsessive–compulsive disorders: OC behaviors, phenotypes and genetics. Autism Research 2009, 2: 293-311. PMID: 20029829, PMCID: PMC3974607, DOI: 10.1002/aur.108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChildChild Development Disorders, PervasiveChild, PreschoolComorbidityDiagnosis, DifferentialDisease Models, AnimalDiseases in TwinsGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansInfantIntellectual DisabilityInterview, PsychologicalNeuropsychological TestsObsessive-Compulsive DisorderPhenotypeQuantitative Trait, HeritableStereotyped BehaviorConceptsAutism spectrum disorderObsessive-compulsive behaviorObsessive-compulsive disorderNovel treatment interventionsFamily genetic studiesAutism spectrumGeneralist genesOC behaviorSpectrum disorderRare genetic variantsASD variesHeritable endophenotypeASD phenotypeCandidate gene studiesNovel genomic technologiesNonparametric linkage analysisInnovative statistical approachChronological ageGenetic mechanismsGenomic technologiesTreatment interventionsGenetic analysisGenetic influencesLinkage analysisGene studiesRisk and Resilience: Early Manipulation of Macaque Social Experience and Persistent Behavioral and Neurophysiological Outcomes
Stevens HE, Leckman JF, Coplan JD, Suomi SJ. Risk and Resilience: Early Manipulation of Macaque Social Experience and Persistent Behavioral and Neurophysiological Outcomes. Journal Of The American Academy Of Child & Adolescent Psychiatry 2009, 48: 114-127. PMID: 19127170, DOI: 10.1097/chi.0b013e318193064c.Peer-Reviewed Original ResearchAdolescentAdolescent BehaviorAnimalsChildChild BehaviorChild DevelopmentChild RearingChild, PreschoolGenotypeHumansInfantInfant, NewbornMacacaMother-Child RelationsNeurophysiologyNeurotransmitter AgentsResilience, PsychologicalRiskRisk FactorsSocial BehaviorSocial EnvironmentStress, PsychologicalTemperament
2007
The role of abnormal neural oscillations in the pathophysiology of co-occurring Tourette syndrome and attention-deficit/hyperactivity disorder
Sukhodolsky DG, Leckman JF, Rothenberger A, Scahill L. The role of abnormal neural oscillations in the pathophysiology of co-occurring Tourette syndrome and attention-deficit/hyperactivity disorder. European Child & Adolescent Psychiatry 2007, 16: 51-59. PMID: 17665283, DOI: 10.1007/s00787-007-1007-3.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderTourette syndromeAbnormal neural oscillationsOscillatory activityHyperactivity disorderAbnormal oscillatory activityThalamo-cortical circuitsSymptoms of ADHDNeural oscillationsNeural oscillatory activityBasal gangliaFunctional abnormalitiesNormal brainThalamocortical regionsThalamocortical oscillationsCortical regionsTransient hyperpolarizationPrefrontal cortexNeural activityNeural communicationPathophysiologyMotor controlSyndromeBrainDisordersNurturing resilient children
Leckman JF, Mayes LC. Nurturing resilient children. Journal Of Child Psychology And Psychiatry 2007, 48: 221-223. PMID: 17355396, DOI: 10.1111/j.1469-7610.2007.01743.x.Peer-Reviewed Original Research
2006
Identification of pyruvate kinase as an antigen associated with Tourette syndrome
Kansy JW, Katsovich L, McIver KS, Pick J, Zabriskie JB, Lombroso PJ, Leckman JF, Bibb JA. Identification of pyruvate kinase as an antigen associated with Tourette syndrome. Journal Of Neuroimmunology 2006, 181: 165-176. PMID: 17011640, PMCID: PMC1853370, DOI: 10.1016/j.jneuroim.2006.08.007.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceAnimalsAntibodies, BacterialAntigensAutoantibodiesBrainChildCross ReactionsHumansImmunohistochemistryLongitudinal StudiesMaleMiceMice, Inbred C57BLMolecular Sequence DataProspective StudiesPyruvate KinaseRatsSeroepidemiologic StudiesStreptococcal InfectionsTicsTourette SyndromeConceptsStreptococcal infectionObsessive-compulsive disorderTourette syndromeAutoimmune targetExacerbated symptomsBeta-hemolytic streptococcal infectionEarly-onset obsessive-compulsive disorderStreptococcal M proteinPediatric populationTic disordersImmune responseSurface antigenInfectious strainsSyndromeInfectionDisordersPyruvate kinaseM proteinPatientsImmunoreactivitySymptomsAntigenAntibodiesGlycolytic enzymesM1 isoformThe normalcy of neurosis: Evolutionary origins of obsessive–compulsive disorder and related behaviors
Feygin DL, Swain JE, Leckman JF. The normalcy of neurosis: Evolutionary origins of obsessive–compulsive disorder and related behaviors. Progress In Neuro-Psychopharmacology And Biological Psychiatry 2006, 30: 854-864. PMID: 16530315, DOI: 10.1016/j.pnpbp.2006.01.009.Peer-Reviewed Original Research