2020
An examination of the relationship between regulatory T cells and symptom flare-ups in children and adolescents diagnosed with chronic tic disorder and Tourette syndrome
Yildirim Z, Karabekiroglu K, Yildiran A, Celiksoy MH, Artukoglu B, Baykal S, Babadağı Z, Leckman J. An examination of the relationship between regulatory T cells and symptom flare-ups in children and adolescents diagnosed with chronic tic disorder and Tourette syndrome. Nordic Journal Of Psychiatry 2020, 75: 18-24. PMID: 32580599, DOI: 10.1080/08039488.2020.1779808.Peer-Reviewed Original ResearchConceptsTS/chronic tic disorderChronic tic disorderSex-matched healthy controlsModerate-severe groupHealthy controlsLymphocyte countTourette syndromeLymphocyte percentagePatient groupTic disordersHC groupControl groupT-helper lymphocyte countYale Global Tic Severity ScaleT helper (TH) (CD4) numberT-lymphocyte countsT lymphocyte numbersT-lymphocyte percentageRegulatory T cellsT cell valuesTic Severity ScaleTreg percentageChildhood-onset neurodevelopmental disorderLymphocyte numbersPhonic ticsAntibodies 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 typesThe prevalence of behavioral and emotional problems among Chinese school children and adolescents aged 6–16: a national survey
Cui Y, Li F, Leckman JF, Guo L, Ke X, Liu J, Zheng Y, Li Y. The prevalence of behavioral and emotional problems among Chinese school children and adolescents aged 6–16: a national survey. European Child & Adolescent Psychiatry 2020, 30: 233-241. PMID: 32172341, DOI: 10.1007/s00787-020-01507-6.Peer-Reviewed Original ResearchConceptsChild Behavior ChecklistEmotional problemsMental health providersNational surveyChinese school childrenLong-term benefitsAchenbach Child Behavior ChecklistHigh prevalenceLarge cohortPediatric psychiatristHealth providersMental disordersMultistage clusterPrevalenceCohortMental healthCBCL scoresOlder cohortBehavior ChecklistYounger cohortsChildrenMaternal perceptions of father involvement among refugee and disadvantaged families in Beirut, Lebanon
Hein S, Bick J, Issa G, Aoude L, Maalouf C, Awar A, Nourallah S, Zonderman AL, Householder S, Katsovich L, Khoshnood K, Moore C, Salah R, Britto PR, Leckman JF, Ponguta LA. Maternal perceptions of father involvement among refugee and disadvantaged families in Beirut, Lebanon. PLOS ONE 2020, 15: e0229670. PMID: 32134961, PMCID: PMC7058288, DOI: 10.1371/journal.pone.0229670.Peer-Reviewed Original ResearchAn integrated program of computer-presented and physical cognitive training exercises for children with attention-deficit/hyperactivity disorder
Wexler BE, Vitulano LA, Moore C, Katsovich L, Smith SD, Rush C, Grantz H, Dong J, Leckman JF. An integrated program of computer-presented and physical cognitive training exercises for children with attention-deficit/hyperactivity disorder. Psychological Medicine 2020, 51: 1524-1535. PMID: 32090720, DOI: 10.1017/s0033291720000288.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderExperimental medicine approachTAU groupMedicine approachHyperactivity disorderWeeks of treatmentCombined subtypeDiagnosis of ADHDClinical trial designHyperactive-impulsive subtypeAttention-deficit/hyperactivity disorderCross-over designDeficit hyperactivity disorderClinical improvementClinical symptomsRandomized crossCognitive dysfunctionCT groupPathophysiological heterogeneityCONSORT recommendationsTrial designResponse rateChange scoresSubtypesTargeted pathologyRisk factors for obsessive–compulsive symptoms. Follow-up of a community-based youth cohort
Macul Ferreira de Barros P, do Rosário MC, Szejko N, Polga N, Requena GL, Ravagnani B, Fatori D, Batistuzzo MC, Hoexter MQ, Rohde LA, Polanczyk GV, Leckman JF, Miguel EC, de Alvarenga PG. Risk factors for obsessive–compulsive symptoms. Follow-up of a community-based youth cohort. European Child & Adolescent Psychiatry 2020, 30: 89-104. PMID: 32076869, DOI: 10.1007/s00787-020-01495-7.Peer-Reviewed Original ResearchConceptsObsessive-compulsive symptomsRisk factorsAbsence of breastfeedingOCS scoresBaseline anxiety disordersPotential risk factorsLarge community cohortLow socioeconomic statusRegression analysisMental health assessmentMaternal stress levelsLower intelligence quotientCommunity cohortChildhood adversityLower ageHigher OCS scoresAnxiety disordersPsychopathological factorsSocioeconomic statusGenetic factorsSignificant predictorsBaselineHealth assessmentScoresAge
2019
Effects of Integrated Brain, Body, and Social (IBBS) intervention on ERP measures of attentional control in children with ADHD
Smith SD, Crowley MJ, Ferrey A, Ramsey K, Wexler BE, Leckman JF, Sukhodolsky DG. Effects of Integrated Brain, Body, and Social (IBBS) intervention on ERP measures of attentional control in children with ADHD. Psychiatry Research 2019, 278: 248-257. PMID: 31233935, PMCID: PMC6637759, DOI: 10.1016/j.psychres.2019.06.021.Peer-Reviewed Original ResearchConceptsBehavioral measuresAttentional controlIntegrated brainGo/No-Go taskGo-P3 latencySlower reaction timesSocial interventionsRobust treatment effectAttentional systemADHD groupERP measuresDifference waveP3 latencyBrain activityADHDTAU groupEEG proceduresHealthy controlsHC groupReaction timeReplication purposesERPTreatment effectsChildrenSecondary goalThe impact of attention deficit hyperactivity disorder in obsessive‐compulsive disorder subjects
Blanco‐Vieira T, Santos M, Ferrão YA, Torres AR, Miguel EC, Bloch MH, Leckman JF, do Rosario MC. The impact of attention deficit hyperactivity disorder in obsessive‐compulsive disorder subjects. Depression And Anxiety 2019, 36: 533-542. PMID: 30990937, DOI: 10.1002/da.22898.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderAdult OCD patientsObsessive-compulsive disorderDeficit hyperactivity disorderOCD patientsClinical characteristicsExact testFeatures of ADHDHyperactivity disorderSubgroup of patientsAdult obsessive-compulsive disorderComorbid attention deficit hyperactivity disorderSpecific clinical featuresCross-sectional studyObsessive-compulsive disorder (OCD) subjectsLogistic regression analysisFisher's exact testBrazilian Research ConsortiumMann-Whitney testAdult patientsRheumatic feverDevelopment of interventionsClinical featuresObsessive-compulsive spectrum disordersLifetime prevalence
2018
Obsessive-Compulsive Symptomatology in Community Youth: Typical Development or a Red Flag for Psychopathology?
Barzilay R, Patrick A, Calkins ME, Moore TM, Wolf DH, Benton TD, Leckman JF, Gur RC, Gur RE. Obsessive-Compulsive Symptomatology in Community Youth: Typical Development or a Red Flag for Psychopathology? Journal Of The American Academy Of Child & Adolescent Psychiatry 2018, 58: 277-286.e4. PMID: 30738554, DOI: 10.1016/j.jaac.2018.06.038.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderMajor psychiatric conditionsObsessive-compulsive symptomsPsychiatric conditionsAssociation of OCSStructured psychiatric interviewSerious psychopathologyRed flagsSuicide ideationMental health helpDepressive episodePsychiatric evaluationPsychiatric interviewLifetime diagnosisPhiladelphia Neurodevelopmental CohortSymptomsSubstantial associationCommunity youthOCS symptomsFemale participantsHigh rateNeurodevelopmental CohortOCD criteriaPsychosisPhenotypic heterogeneityDe Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis
Wang S, Mandell JD, Kumar Y, Sun N, Morris MT, Arbelaez J, Nasello C, Dong S, Duhn C, Zhao X, Yang Z, Padmanabhuni SS, Yu D, King RA, Dietrich A, Khalifa N, Dahl N, Huang AY, Neale BM, Coppola G, Mathews CA, Scharf JM, Study T, Abdulkadir M, Arbelaez J, Bodmer B, Bromberg Y, Brown L, Cheon K, Coffey B, Deng L, Dietrich A, Dong S, Duhn C, Elzerman L, Fernandez T, Fremer C, Garcia-Delgar B, Gilbert D, Grice D, Hagstrøm J, Hedderly T, Heiman G, Heyman I, Hoekstra P, Hong H, Huyser C, Kim E, Kim Y, Kim Y, King R, Koh Y, Kook S, Kuperman S, Leventhal B, Ludolph A, Madruga-Garrido M, Mandell J, Maras A, Mir P, Morer A, Morris M, Müller-Vahl K, Münchau A, Murphy T, Nasello C, Plessen K, Poisner H, Roessner V, Sanders S, Shin E, Song D, Song J, State M, Sun N, Thackray J, Tischfield J, Tübing J, Visscher F, Wanderer S, Wang S, Willsey A, Woods M, Xing J, Zhang Y, Zhao X, Zinner S, Initiative T, Androutsos C, Barta C, Farkas L, Fichna J, Georgitsi M, Janik P, Karagiannidis I, Koumoula A, Nagy P, Paschou P, Puchala J, Rizzo R, Szejko N, Szymanska U, Tarnok Z, Tsironi V, Wolanczyk T, Zekanowski C, Genetics T, Barr C, Batterson J, Berlin C, Bruun R, Budman C, Cath D, Chouinard S, Coppola G, Cox N, Darrow S, Davis L, Dion Y, Freimer N, Grados M, Hirschtritt M, Huang A, Illmann C, Kurlan R, Leckman J, Lyon G, Malaty I, Mathews C, MacMahon W, Neale B, Okun M, Osiecki L, Pauls D, Posthuma D, Ramensky V, Robertson M, Rouleau G, Sandor P, Scharf J, Singer H, Smit J, Sul J, Yu D, Fernandez T, Buxbaum J, De Rubeis S, Grice D, Xing J, Heiman G, Tischfield J, Paschou P, Willsey A, State M. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis. Cell Reports 2018, 24: 3441-3454.e12. PMID: 30257206, PMCID: PMC6475626, DOI: 10.1016/j.celrep.2018.08.082.Peer-Reviewed Original ResearchConceptsCell polarityNumber variantsSequence variantsDe novo damaging variantsDe novoDe novo sequencesCopy number variantsNovo sequencesWhole-exome sequencingDamaging variantsRisk genesGenesCommon pathwayNovoSignificant overlapVariantsTriosGenetic riskSequencingCELSR3PathwayPolaritySequenceSignificant excessFamilyAdaptive treatment strategies for children and adolescents with Obsessive-Compulsive Disorder: A sequential multiple assignment randomized trial
Fatori D, de Bragança Pereira CA, Asbahr FR, Requena G, Alvarenga PG, de Mathis MA, Rohde LA, Leckman JF, March JS, Polanczyk GV, Miguel EC, Shavitt RG. Adaptive treatment strategies for children and adolescents with Obsessive-Compulsive Disorder: A sequential multiple assignment randomized trial. Journal Of Anxiety Disorders 2018, 58: 42-50. PMID: 30025255, DOI: 10.1016/j.janxdis.2018.07.002.Peer-Reviewed Original ResearchConceptsGroup cognitive behavioral therapySequential multiple assignmentTreatment failureInitial treatmentBaseline Yale-Brown ObsessiveChildhood OCDEffective initial treatmentProvision of treatmentCompulsive Scale scoresCognitive behavioral therapyAdaptive treatment strategiesYale-Brown ObsessiveSame regimenObsessive-compulsive disorderTreatment strategiesSymptom reductionPrimary analysisScale scoreFluoxetineTime pointsWeeksTreatmentChildrenEffect sizeTrialsA multicenter examination and strategic revisions of the Yale Global Tic Severity Scale
McGuire JF, Piacentini J, Storch EA, Murphy TK, Ricketts EJ, Woods DW, Walkup JW, Peterson AL, Wilhelm S, Lewin AB, McCracken JT, Leckman JF, Scahill L. A multicenter examination and strategic revisions of the Yale Global Tic Severity Scale. Neurology 2018, 90: e1711-e1719. PMID: 29653992, PMCID: PMC5952973, DOI: 10.1212/wnl.0000000000005474.Peer-Reviewed Original ResearchConceptsTic symptom severityTic scoreTIC numbersYale Global Tic Severity Scale (YGTSS) scoresSymptom severityYale Global Tic Severity ScaleYGTSS total tic scoreTotal tic scoreSimilar clinical characteristicsInternal consistencySeverity Scale scoreCross-sectional studyTic Severity ScaleDelphi consensus processClinical characteristicsPhonic ticsTic disordersMulticenter examinationImpairment scoresGood internal consistencySeverity ScaleScale scoreSymptom ChecklistDiagnostic InterviewStrong internal consistencyAttention and executive functions computer training for attention-deficit/hyperactivity disorder (ADHD): results from a randomized, controlled trial
Bikic A, Leckman JF, Christensen TØ, Bilenberg N, Dalsgaard S. Attention and executive functions computer training for attention-deficit/hyperactivity disorder (ADHD): results from a randomized, controlled trial. European Child & Adolescent Psychiatry 2018, 27: 1563-1574. PMID: 29644473, DOI: 10.1007/s00787-018-1151-y.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderCognitive functionMultiple cognitive functionsComputer training programCognitive trainingHyperactivity disorderComputer trainingTraining programOutcome measuresFunctional outcome measuresIntervention groupTrainingChildrenAttentionMeasuresSecondary outcome measuresDate of registrationControl groupSignificant beneficial effectDisordersInterventionSingle-blind trialSignificant effectOutcomesTrialsEfficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry
Martinez-Ramirez D, Jimenez-Shahed J, Leckman JF, Porta M, Servello D, Meng FG, Kuhn J, Huys D, Baldermann JC, Foltynie T, Hariz MI, Joyce EM, Zrinzo L, Kefalopoulou Z, Silburn P, Coyne T, Mogilner AY, Pourfar MH, Khandhar SM, Auyeung M, Ostrem JL, Visser-Vandewalle V, Welter ML, Mallet L, Karachi C, Houeto JL, Klassen BT, Ackermans L, Kaido T, Temel Y, Gross RE, Walker HC, Lozano AM, Walter BL, Mari Z, Anderson WS, Changizi BK, Moro E, Zauber SE, Schrock LE, Zhang JG, Hu W, Rizer K, Monari EH, Foote KD, Malaty IA, Deeb W, Gunduz A, Okun MS. Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry. JAMA Neurology 2018, 75: 353-359. PMID: 29340590, PMCID: PMC5885852, DOI: 10.1001/jamaneurol.2017.4317.Peer-Reviewed Original ResearchConceptsDeep brain stimulationGlobus pallidus internusTourette syndromeDBS implantationBrain stimulationAdverse eventsOutcome of DBSSafety of DBSYale Global Tic Severity Scale (YGTSS) scoresPosterior globus pallidus internusOverall adverse event rateYale Global Tic Severity ScaleStimulation-induced adverse effectsMedically refractory symptomsImportant adverse eventsAdverse event ratesRefractory Tourette syndromeSeverity Scale scoreTic Severity ScaleSelf-injurious behaviorRefractory symptomsSymptomatic improvementIntracranial hemorrhageObsessive-compulsive disorderInternal capsule
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 interviewsA double-blind randomized pilot trial comparing computerized cognitive exercises to Tetris in adolescents with attention-deficit/hyperactivity disorder
Bikic A, Christensen TØ, Leckman JF, Bilenberg N, Dalsgaard S. A double-blind randomized pilot trial comparing computerized cognitive exercises to Tetris in adolescents with attention-deficit/hyperactivity disorder. Nordic Journal Of Psychiatry 2017, 71: 455-464. PMID: 28598701, DOI: 10.1080/08039488.2017.1328070.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderComputerized cognitive exercisesCognitive exercisesHyperactivity disorderComputer game TetrisSignificant intra-group changesADHD symptom measuresSignificant group differencesLarge effect sizesDouble-blind randomized pilot trialBrain trainingSustained attentionCognitive testsGame TetrisMotivation questionnaireHome-based interventionGroup differencesSignificant beneficial effectRandomized pilot trialActive placeboIntra-group changesTetrisAdolescentsEffect sizeBeneficial effectsRare 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 riskVariantsDe Novo Coding Variants Are Strongly Associated with Tourette Disorder
Willsey AJ, Fernandez TV, Yu D, King RA, Dietrich A, Xing J, Sanders SJ, Mandell JD, Huang AY, Richer P, Smith L, Dong S, Samocha KE, Genetics T, Abdulkadir M, Bohnenpoll J, Bromberg Y, Brown L, Cheon K, Coffey B, Deng L, Dietrich A, Dong S, Elzerman L, Fernandez T, Fründt O, Garcia-Delgar B, Gedvilaite E, Gilbert D, Grice D, Hagstrøm J, Hedderly T, Heiman G, Heyman I, Hoekstra P, Hong H, Huyser C, Ibanez-Gomez L, Kim Y, Kim Y, King R, Koh Y, Kook S, Kuperman S, Lamerz A, Leventhal B, Ludolph A, da Silva C, Madruga-Garrido M, Mandell J, Maras A, Mir P, Morer A, Münchau A, Murphy T, Nasello C, Openneer T, Plessen K, Richer P, Roessner V, Sanders S, Shin E, Sival D, Smith L, Song D, Song J, State M, Stolte A, Sun N, Tischfield J, Tübing J, Visscher F, Walker M, Wanderer S, Wang S, Willsey A, Woods M, Xing J, Zhang Y, Zhou A, Zinner S, Genetics T, Barr C, Batterson J, Berlin C, Bruun R, Budman C, Cath D, Chouinard S, Coppola G, Cox N, Darrow S, Davis L, Dion Y, Freimer N, Grados M, Hirschtritt M, Huang A, Illmann C, Kurlan R, Leckman J, Lyon G, Malaty I, Mathews C, MaMahon W, Neale B, Okun M, Osiecki L, Pauls D, Posthuma D, Ramensky V, Robertson M, Rouleau G, Sandor P, Scharf J, Singer H, Smit J, Sul J, Yu D, Neale B, Coppola G, Mathews C, Tischfield J, Scharf J, State M, Heiman G. De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron 2017, 94: 486-499.e9. PMID: 28472652, PMCID: PMC5769876, DOI: 10.1016/j.neuron.2017.04.024.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingTourette's disorderDamaging variantsLikely gene-disrupting variantsComplex neurodevelopmental disorderClinical casesUnrelated probandsNeurodevelopmental disordersDe novo damaging variantsDisordersRisk genesGenetic cohortsConsistent evidenceCoding variantReplication sampleProbandsInternational ConsortiumCohortVariants