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
Behavioral, 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
2010
The 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 areasElevated expression of MCP-1, IL-2 and PTPR-N in basal ganglia of Tourette syndrome cases
Morer A, Chae W, Henegariu O, Bothwell AL, Leckman JF, Kawikova I. Elevated expression of MCP-1, IL-2 and PTPR-N in basal ganglia of Tourette syndrome cases. Brain Behavior And Immunity 2010, 24: 1069-1073. PMID: 20193755, DOI: 10.1016/j.bbi.2010.02.007.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAutopsyBasal GangliaChemokine CCL2FemaleHumansInterferon-gammaInterleukin-1betaInterleukin-2Leukocyte Common AntigensMaleMiddle AgedPolymerase Chain ReactionReceptor-Like Protein Tyrosine Phosphatases, Class 2Receptor-Like Protein Tyrosine Phosphatases, Class 8RecoverinRNATourette SyndromeConceptsMCP-1IL-2Tourette syndromePost-mortem specimenBasal gangliaElevated expressionPost-infectious autoimmunityAdult TS patientsChronic inflammatory processEvidence of inflammationBasal ganglia areaInterleukin-1 βCentral nervous systemChemotactic factor-1TS casesReverse transcription-polymerase chain reaction analysisTranscription-polymerase chain reaction analysisReal-time reverse transcription-polymerase chain reaction analysisBrain tissue sectionsInflammatory factorsControl subjectsGanglia areaInflammatory processInterleukin-2TS patients
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 controlSyndromeBrainDisorders
2005
Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome
Kalanithi PS, Zheng W, Kataoka Y, DiFiglia M, Grantz H, Saper CB, Schwartz ML, Leckman JF, Vaccarino FM. Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 13307-13312. PMID: 16131542, PMCID: PMC1201574, DOI: 10.1073/pnas.0502624102.Peer-Reviewed Original ResearchConceptsTourette syndromeNeuron distributionCalcium-binding protein parvalbuminNeuron numberT subjectsLower neuron numberGlobus pallidus pars externaParvalbumin-positive interneuronsTotal neuron numberUnbiased stereological techniquesChildhood neuropsychiatric disordersBasal ganglia tissueGABAergic neuronsGPi neuronsBasal gangliaCortico-striatoGlobus pallidusProtein parvalbuminThalamic circuitryGanglion tissueVocal ticsNormal controlsPutamen volumePars externaImaging studies
2003
Basal Ganglia Volumes in Patients With Gilles de la Tourette Syndrome
Peterson BS, Thomas P, Kane MJ, Scahill L, Zhang H, Bronen R, King RA, Leckman JF, Staib L. Basal Ganglia Volumes in Patients With Gilles de la Tourette Syndrome. JAMA Psychiatry 2003, 60: 415-424. PMID: 12695320, DOI: 10.1001/archpsyc.60.4.415.Peer-Reviewed Original ResearchConceptsBasal ganglia volumesBasal gangliaCaudate nucleus volumeTourette syndromeGanglia volumesObsessive-compulsive disorderLenticular nucleus volumesTic symptomsNucleus volumeGilles dePathophysiology of TSPrior neuroleptic exposureHealthy control subjectsSeverity of ticsComorbid obsessive-compulsive disorderGreat clinical relevanceAttention-deficit/hyperactivity disorder (ADHD) symptomsHyperactivity disorder symptomsRepeated-measures analysisNeuroleptic exposureControl subjectsFunctional disturbancesTrait abnormalityClinical relevanceGanglia
2001
Tic disorders: when habit forming neural systems form habits of their own?
Leckman JF, Yeh CB, Cohen DJ. Tic disorders: when habit forming neural systems form habits of their own? Journal Of The Chinese Medical Association 2001, 64: 669-92. PMID: 11922487.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderTourette syndromeAttention-deficit/hyperactivity disorderBasal gangliaIntolerable side effectsSubgroup of patientsLong-term outcomesAlpha-adrenergic agentsMajor affective disordersSpecific brain circuitsNew therapeutic directionDeficit/hyperactivity disorderAutoimmune mechanismsEarly brain developmentComorbid conditionsAtypical neurolepticsClinical neuroscience researchClinical trialsPrevalent disorderChildhood onsetClinical careMarked impairmentSide effectsPharmacological techniquesAffective disorders
1998
A Functional Magnetic Resonance Imaging Study of Tic Suppression in Tourette Syndrome
Peterson BS, Skudlarski P, Anderson AW, Zhang H, Gatenby JC, Lacadie CM, Leckman JF, Gore JC. A Functional Magnetic Resonance Imaging Study of Tic Suppression in Tourette Syndrome. JAMA Psychiatry 1998, 55: 326-333. PMID: 9554428, DOI: 10.1001/archpsyc.55.4.326.Peer-Reviewed Original ResearchConceptsTic suppressionTourette syndromeTic symptomsBasal gangliaPathogenesis of ticsVoluntary tic suppressionMagnetic resonance imaging studyResonance imaging studyFunctional magnetic resonance imaging studySubcortical neural circuitsFunctional magnetic resonance imagingMagnetic resonance imagingConnected cortical regionsRegional signal changesImpaired modulationSignal changesFunctional debilityNeuronal activityResonance imagingAdult subjectsImaging studiesCortical regionsNeuropsychiatric disordersNeural circuitsSyndrome
1993
Reduced basal ganglia volumes in Tourette's syndrome using three-dimensional reconstruction techniques from magnetic resonance images.
Peterson B, Riddle MA, Cohen DJ, Katz LD, Smith JC, Hardin MT, Leckman JF. Reduced basal ganglia volumes in Tourette's syndrome using three-dimensional reconstruction techniques from magnetic resonance images. Neurology 1993, 43: 941-9. PMID: 8492950, DOI: 10.1212/wnl.43.5.941.Peer-Reviewed Original ResearchConceptsBasal gangliaSyndrome patientsNormal controlsReduced basal ganglia volumeBasal ganglia volumesTourette syndrome patientsGlobus pallidus nucleusSmaller mean volumesPathogenesis of TSEsNeuroleptic exposureGanglia volumesPallidus nucleusNeuroradiologic studiesTourette syndromeVolumetric asymmetryMean volumeMagnetic resonance imagesGangliaAxial imagesSocioeconomic statusAsymmetry indexSyndromeResonance imagesVolume reductionMR scanner
1990
Gilles de La Tourette's syndrome and some forms of obsessive-compulsive disorder may share a common genetic diathesis.
Leckman JF, Chittenden EH. Gilles de La Tourette's syndrome and some forms of obsessive-compulsive disorder may share a common genetic diathesis. L Encéphale 1990, 16 Spec No: 321-3. PMID: 2209489.Peer-Reviewed Original ResearchConceptsPathophysiology of TSGilles de la Tourette's syndromeObsessive-compulsive disorderLa Tourette's syndromeTourette syndromeOCD patientsCerebrospinal fluid studiesRecent neuropathological studiesEndogenous opioid peptidesMesocortical dopaminergic systemCases of OCDCSF dynorphinNeuropathological studiesCommon genetic diathesisRaphe nucleusBasal gangliaSerotoninergic systemSerotonergic systemClinical studiesDopaminergic systemCommon neural substrateTS patientsNeuropharmacological studiesOpioid peptidesNormal controls
1988
Elevated CSF dynorphin A [1–8] in Tourette's syndrome
Leckman JF, Riddle MA, Berrettini WH, Anderson GM, Hardin M, Chappell P, Bissette G, Nemeroff CB, Goodman WK, Cohen DJ. Elevated CSF dynorphin A [1–8] in Tourette's syndrome. Life Sciences 1988, 43: 2015-2023. PMID: 2463450, DOI: 10.1016/0024-3205(88)90575-9.Peer-Reviewed Original ResearchConceptsPathobiology of TSTourette syndromeNeuroanatomic distributionEndogenous opioidsNeuropathological studiesObsessive-compulsive disorderPrevalence of TSBehavioral effectsPost-mortem brain studiesPathophysiology of TSGilles de la Tourette's syndromeCentral dopaminergic neuronsRecent neuropathological studiesLevels of dynorphinSevere Tourette syndromeBasal ganglia structuresChronic neuropsychiatric disorderLa Tourette's syndromeCentral monoaminergicCSF dynorphinElevated CSFStriatal fibersCSF studiesDopaminergic neuronsBasal ganglia