2025
Predictors and Moderators of Long-Term Outcome of Persons at Clinical High Risk for Psychosis: Methods and Preliminary Data
Cadenhead K, Kennedy L, Mirzakhanian H, Addington J, Bearden C, Cannon T, Carrión R, Keshavan M, Mathalon D, Perkins D, Stone W, Walker E, Woods S. Predictors and Moderators of Long-Term Outcome of Persons at Clinical High Risk for Psychosis: Methods and Preliminary Data. Schizophrenia Bulletin 2025, sbaf133. PMID: 40856400, DOI: 10.1093/schbul/sbaf133.Peer-Reviewed Original ResearchClinical high riskClinical high-risk criteriaLong-term outcomesNorth American Prodrome Longitudinal Study sitesClinical high-risk participantsRates of affective disordersHigh riskLife courseNon-converter groupHigh-risk youthAssessment of individualsPsychosis statesAffective disordersPsychosocial functioningPsychosisTrajectory of diagnosisLonger-term outcomesClinical/functional outcomesLong-term assessmentGeneral populationBaseline dataParticipantsPreliminary dataEarly dataPersonsIdentifying individuals at clinical high risk for psychosis using a battery of tasks sensitive to symptom mechanisms
Williams T, Gold J, Waltz J, Schiffman J, Ellman L, Strauss G, Walker E, Woods S, Powers A, Kenney J, Pappu M, Corlett P, Tran T, Silverstein S, Zinbarg R, Mittal V. Identifying individuals at clinical high risk for psychosis using a battery of tasks sensitive to symptom mechanisms. Translational Psychiatry 2025, 15: 311. PMID: 40849429, PMCID: PMC12375010, DOI: 10.1038/s41398-025-03539-5.Peer-Reviewed Original ResearchConceptsCHR-P individualsClinical high riskCHR-PClinical InterviewComputerized assessmentAssessment of psychosis riskStructured Clinical InterviewRisk calculator scoresNeurocognitive mechanismsPsychosis symptomsPsychosis riskBehavioral tasksUnique predictorsMental disordersTask batteryPsychosisTask variablesComparison groupHealthy controlsRisk severityUpdate beliefsTaskMultinomial logistic regressionConsortium studyIndividualsPrediction of antipsychotic medication inception in antipsychotic-naive youth at clinical high risk for psychosis
Mukhtar H, Zhou D, Farina E, Saxena A, Cahill J, Addington J, Bearden C, Cadenhead K, Cannon T, Cornblatt B, Keshwan M, Mathalon D, Perkins D, Stone W, Cho Y, Powers A, Walker E, Woods S. Prediction of antipsychotic medication inception in antipsychotic-naive youth at clinical high risk for psychosis. Psychological Medicine 2025, 55: e241. PMID: 40842369, PMCID: PMC12404330, DOI: 10.1017/s0033291725101372.BooksClinical high riskCHR-PLifetime historyAugmentation of antidepressant treatmentComorbid major depressionAP useAntidepressant treatmentPositive symptomsMajor depressionAP medicationNAPLS-2Independent predictorsCHR-P.High riskBaseline clinical variablesPsychosisBaseline predictorsClinical variablesParticipantsBaseline characteristicsUnivariate analysisLogistic regression modelsObservational cohortMultivariate analysisAP initiationIncidence, Prevalence, and Stability of Remission in Individuals With Clinical High Risk for Psychosis
Seitz-Holland J, Jacobs G, Reinen J, Mathalon D, Corcoran C, Reichenberg A, Vangel M, Glynn R, Penzel N, Cho K, Castro E, Haidar A, Addington J, Kapur T, Bouix S, Bearden C, Kane J, McGorry P, Woods S, Nelson B, Kahn R, Shenton M, Cecchi G, Pasternak O. Incidence, Prevalence, and Stability of Remission in Individuals With Clinical High Risk for Psychosis. JAMA Network Open 2025, 8: e2525644. PMID: 40762913, PMCID: PMC12326281, DOI: 10.1001/jamanetworkopen.2025.25644.Peer-Reviewed Original ResearchConceptsClinical high riskClinical high-risk statusAssociated with higher likelihoodModified Global AssessmentLikelihood of remissionRemission criteriaPositive symptomsGlobal Assessment of FunctioningScale of Prodromal SymptomsRemission incidenceModified Global Assessment of FunctioningAssessment of functioningFollow-upStability of remissionHigh riskHigher likelihood of remissionAntidepressant medicationFunctional remissionCognitive variablesCognitive performanceMain OutcomesClinical servicesStudy 3Follow-up visitCohort studyVictimization and engagement with the legal system among individuals at clinical high risk (CHR) for psychosis
Du A, Kennedy L, Addington J, Bearden C, Cannon T, Carrion R, Keshavan M, Mathalon D, Perkins D, Stone W, Walker E, Woods S, Cadenhead K. Victimization and engagement with the legal system among individuals at clinical high risk (CHR) for psychosis. Schizophrenia Research 2025, 284: 7-15. PMID: 40737766, DOI: 10.1016/j.schres.2025.07.015.Peer-Reviewed Original ResearchLegal systemLegal historyPerpetrators of crimesVictims of crimeHistory of victimizationClinical high-risk youthClinical high riskHistorical risk factorsReport victimizationLegal issuesVictimsCrimeComorbid mental illnessMental illnessYouthClinical high-risk participantsPsychotic illnessLife risk factorsPsychosis symptomsPerpetratorsViolencePsychosisHealthy controlsStudy-3EngagementThe moderating role of lifetime social engagement on the relationship between C-reactive protein and negative symptoms among young adults at clinical high risk for psychosis
Goldsmith D, Yuan Q, Addington J, Bearden C, Cadenhead K, Cannon T, Carrión R, Keshavan M, Mathalon D, Perkins D, Stone W, Tsuang M, Woods S, Walker E, Ku B. The moderating role of lifetime social engagement on the relationship between C-reactive protein and negative symptoms among young adults at clinical high risk for psychosis. Brain Behavior And Immunity 2025, 129: 890-897. PMID: 40730261, PMCID: PMC12360851, DOI: 10.1016/j.bbi.2025.07.023.Peer-Reviewed Original ResearchConceptsScale of Psychosis-risk SymptomsNegative symptomsCHR-P groupClinical high riskCHR-PC-reactive proteinAssociated with negative symptomsNorth American Prodrome Longitudinal StudySocial engagementDevelopment of negative symptomsPsychosis-risk symptomsSimple slope analysesCHR-P individualsYoung adultsHealthy controlsCHR-P subjectsLevels of social engagementSocial engagement levelsEarly developmental periodDepressive symptomsSimple slopesHC subjectsPsychosisHigh riskC-reactive protein valuesMultisensory overweighting of perceptual priors relates to positive symptoms in individuals at clinical high risk of psychosis
Pokorny V, Ellman L, Strauss G, Walker E, Woods S, Powers A, Corlett P, Silverstein S, Waltz J, Gold J, Schiffman J, Mittal V. Multisensory overweighting of perceptual priors relates to positive symptoms in individuals at clinical high risk of psychosis. Journal Of Vision 2025, 25: 2130. DOI: 10.1167/jov.25.9.2130.Peer-Reviewed Original ResearchExploring the pathways between early auditory processing, processing speed, social cognition, and negative symptoms on social functioning in individuals at clinical high risk for psychosis: A structural equation modeling approach
Carrión R, John M, Dorvil S, Auther A, McLaughlin D, Arnovitz M, Bachman P, Belger A, Duncan E, Hamilton H, Johannesen J, Ku B, Light G, Niznikiewicz M, Roach B, Addington J, Bearden C, Cadenhead K, Cannon T, Keshavan M, Perkins D, Stone W, Tsuang M, Walker E, Woods S, Mathalon D, Cornblatt B. Exploring the pathways between early auditory processing, processing speed, social cognition, and negative symptoms on social functioning in individuals at clinical high risk for psychosis: A structural equation modeling approach. Biological Psychiatry 2025 PMID: 40633882, DOI: 10.1016/j.biopsych.2025.06.033.Peer-Reviewed Original ResearchClinical high riskNegative symptomsEvent-related potentialsCHR-P individualsCHR-PPsychosis onsetSocial cognitionMismatch negativityStructural equation modelingSocial functioningProcessing deficitsProcessing speedNorth American Prodrome Longitudinal StudyEarly information processing deficitsAssociated with social functioningAuditory processingInformation processing deficitsSocial functioning difficultiesPoor social functioningSocial functioning impairmentAuditory event-related potentialsAuditory processing deficitsEarly auditory processingEarly intervention strategiesNeurophysiological deficitsCognitive subtypes in youth at clinical high risk for psychosis
Yassin W, Green J, Keshavan M, del Re E, Addington J, Bearden C, Cadenhead K, Cannon T, Cornblatt B, Mathalon D, Perkins D, Walker E, Woods S, Stone W. Cognitive subtypes in youth at clinical high risk for psychosis. Psychiatry And Clinical Neurosciences 2025 PMID: 40600477, DOI: 10.1111/pcn.13861.Peer-Reviewed Original ResearchClinical high riskCognitive subtypesWorking memoryClinical high-risk groupWorking memory domainsConversion statusPsychotic disordersCognitive clustersVerbal abilityCHR patientsCognitive measuresMemory domainCognitive domainsNAPLS-2Cognitive trajectoriesPsychosisImpairment groupIntact groupHealthy controlsFunction trajectoriesIntervention strategiesBaseline differencesMemoryHigh riskMonths of follow-upFunctional Correlates of Atypical Visuoperceptual Organization in a Multisite Clinical High-Risk Sample
Pokorny V, Tran T, Williams T, Kenney J, Silverstein S, Gold J, Waltz J, Schiffman J, Ellman L, Strauss G, Walker E, Woods S, Powers A, Corlett P, Mittal V. Functional Correlates of Atypical Visuoperceptual Organization in a Multisite Clinical High-Risk Sample. Journal Of Psychopathology And Clinical Science 2025, 134: 527-539. PMID: 40193439, PMCID: PMC12162206, DOI: 10.1037/abn0000992.Peer-Reviewed Original ResearchConceptsClinical high riskPsychotic-like Experiences groupClinical high-risk statusClinical high-risk samplesMeasures of cognitive abilityClinical high-risk groupHigh-risk sampleMeasuring perceptual organizationFaces taskPsychotic disordersPerceptual priorsCognitive abilitiesCognitive functionClinical groupsPerceptual organizationHealthy control groupContext-sensitiveSocial functioningTwo-tone imagesTarget circleSymbolic codeEbbinghausFunctional correlatesTaskParticipantsThe electroencephalography protocol for the Accelerating Medicines Partnership® Schizophrenia Program: Reliability and stability of measures
Mathalon D, Nicholas S, Roach B, Billah T, Lavoie S, Whitford T, Hamilton H, Addamo L, Anohkin A, Bekinschtein T, Belger A, Buccilli K, Cahill J, Carrión R, Damiani S, Dzafic I, Ebdrup B, Izyurov I, Jarcho J, Jenni R, Jo A, Kerins S, Lee C, Martin E, Mayol-Troncoso R, Niznikiewicz M, Parvaz M, Pogarell O, Prieto-Montalvo J, Rabin R, Roalf D, Rogers J, Salisbury D, Shaik R, Shankman S, Stevens M, Suen Y, Swann N, Tang X, Thompson J, Tso I, Wenzel J, Zhou J, Addington J, Alameda L, Arango C, Breitborde N, Broome M, Cadenhead K, Calkins M, Castillo-Passi R, Chen E, Choi J, Conus P, Corcoran C, Cornblatt B, Diaz-Caneja C, Ellman L, Fusar-Poli P, Gaspar P, Gerber C, Glenthøj L, Horton L, Hui C, Kambeitz J, Kambeitz-Ilankovic L, Keshavan M, Kim M, Kim S, Koutsouleris N, Kwon J, Langbein K, Mamah D, Mittal V, Nordentoft M, Pearlson G, Perez J, Perkins D, Powers A, Sabb F, Schiffman J, Shah J, Silverstein S, Smesny S, Stone W, Strauss G, Upthegrove R, Verma S, Wang J, Wolf D, Zhang T, Bouix S, Pasternak O, Cho K, Coleman M, Dwyer D, Nunez A, Tamayo Z, Wood S, Kahn R, Kane J, McGorry P, Bearden C, Nelson B, Woods S, Shenton M, Light G. The electroencephalography protocol for the Accelerating Medicines Partnership® Schizophrenia Program: Reliability and stability of measures. Schizophrenia 2025, 11: 85. PMID: 40480970, PMCID: PMC12144291, DOI: 10.1038/s41537-025-00622-0.Peer-Reviewed Original ResearchEvent-related oscillationsEEG power spectral densityClinical outcomesMarkers of illness progressionRisks of antipsychotic drugsAuditory steady state responsePredictor of clinical outcomeMismatch negativityVariable clinical outcomesControlled clinical trialsClinical high riskTest-retest reliabilitySecondary outcome measuresEEG-based measuresVisual P300Antipsychotic drugsPaired t-testEEG protocolsClinical trialsEffective medicationsInterim analysisHigh riskPersonalized treatmentTraditional frequency bandsCHR individualsDigital health technologies in the accelerating medicines Partnership® Schizophrenia Program
Wigman J, Ching A, Chung Y, Eichi H, Lane E, Langholm C, Vaidyam A, Byun A, Haidar A, Hartmann J, Nunez A, Dwyer D, Nasarudin A, Borders O, Scott I, Tamayo Z, Matneja P, Cho K, Addington J, Alameda L, Arango C, Breitborde N, Broome M, Cadenhead K, Calkins M, Chen E, Choi J, Conus P, Corcoran C, Cornblatt B, Diaz-Caneja C, Ellman L, Fusar-Poli P, Gaspar P, Gerber C, Glenthøj L, Horton L, Hui C, Kambeitz J, Kambeitz-Ilankovic L, Keshavan M, Kim S, Koutsouleris N, Langbein K, Mamah D, Mathalon D, Mittal V, Nordentoft M, Pearlson G, Perez J, Perkins D, Powers A, Rogers J, Sabb F, Schiffman J, Shah J, Silverstein S, Smesny S, Yassin W, Stone W, Strauss G, Thompson J, Upthegrove R, Verma S, Wang J, Wolf D, Wolff P, Rowland L, D’Alfonso S, Pasternak O, Bouix S, McGorry P, Kahn R, Kane J, Bearden C, Woods S, Shenton M, Nelson B, Baker J, Torous J. Digital health technologies in the accelerating medicines Partnership® Schizophrenia Program. Schizophrenia 2025, 11: 83. PMID: 40461469, PMCID: PMC12134270, DOI: 10.1038/s41537-025-00599-w.Peer-Reviewed Original ResearchDigital componentsDigital health technologiesSmartphone-based digital phenotypingNovel digital health technologiesClinical high riskDigital phenotypingDigital dataHealth technologiesPredictive of transition to psychosisReal-life experiencesSchizophrenia ProgramDaily lifeTransition to psychosisPassive dataEpisode of psychosisPsychosis transitionMapping of experiencesTechnologyHigh riskMeta-analytic studiesCollaborative projectIncreased face perception in individuals at clinical high-risk for psychosis: mechanisms, sex differences, and clinical correlates
Tran T, Keane B, Thompson J, Robinson B, Kenney J, Williams T, Waltz J, Levin J, Kafadar E, Gold J, Schiffman J, Ellman L, Walker E, Strauss G, Mittal V, Zinbarg R, Corlett P, Powers A, Woods S, Silverstein S. Increased face perception in individuals at clinical high-risk for psychosis: mechanisms, sex differences, and clinical correlates. Schizophrenia 2025, 11: 74. PMID: 40355455, PMCID: PMC12069608, DOI: 10.1038/s41537-025-00624-y.Peer-Reviewed Original ResearchClinical high riskCHR participantsCHR groupPhase of psychotic illnessAssessment of psychosis riskSevere positive symptomsGender of facesAssess response biasClinical correlatesPositive symptomsPsychiatric controlsPsychosis riskPsychotic illnessAccuracy of perceptionFace perceptionScrambled conditionPerceptual sensitivityPoorer roleResponse biasFace testPerceptual organizationComputerized assessmentSex differencesAltered visual perceptionPsychosisAltered brain activation during memory retrieval mediates the relationship between developmental trauma and psychotic symptom severity
Mason A, Palmer W, Cao H, Addington J, Bearden C, Cadenhead K, Cornblatt B, Perkins D, Mathalon D, Walker E, Woods S, Cannon T. Altered brain activation during memory retrieval mediates the relationship between developmental trauma and psychotic symptom severity. Schizophrenia Research 2025, 281: 115-121. PMID: 40328092, DOI: 10.1016/j.schres.2025.04.034.Peer-Reviewed Original ResearchConceptsInferior parietal lobe activityPsychotic symptom severityParietal lobe activityDevelopmental traumaDelusion severityHallucination severityMemory taskNeurocognitive measuresMemory processesMemory performanceSymptom severityScale of Psychosis-risk SymptomsNorth American Prodrome Longitudinal StudyPoorer episodic memory performanceRisk of psychotic symptomsPaired-associate memory taskAssociated with memory processingMemory-associated regionsTrauma-exposed individualsEpisodic memory processesEpisodic memory tasksPsychosis-risk symptomsClinical high riskEpisodic memory performanceSubclinical delusionsTrajectories of positive symptoms and suicidality in individuals at clinical high risk for psychosis
Deng W, MacNutt C, Addington J, Bearden C, Cadenhead K, Carrión R, Keshavan M, Mathalon D, Perkins D, Stone W, Walker E, Woods S, Cannon T. Trajectories of positive symptoms and suicidality in individuals at clinical high risk for psychosis. Journal Of Affective Disorders 2025, 384: 208-213. PMID: 40334865, DOI: 10.1016/j.jad.2025.05.023.Peer-Reviewed Original ResearchConceptsPositive symptomsClinical high riskSuicidal ideationCHR-PMeasures of suicidal ideationEarly stages of psychosisPersistence of suicidal ideationSeverity of depressive symptomsPositive symptom severityAssessment timepointsCHR-P participantsEmergence of suicidalityStages of psychosisCHR-P populationTargeted suicide prevention strategiesPsychotic disordersEarly psychosisSuicide prevention strategiesDepressive symptomsSymptom severityPsychosisIdeationDelusionsSuicideHallucinations511. Associations of Cognitive Functions With EEG-Based Event-Related Potentials and Oscillations in Individuals at Clinical High-Risk for Psychosis: A Canonical Correlation Analysis of NAPLS2 Data
Hua J, Roach B, Hamilton H, Bachman P, Belger A, Carrion R, Duncan E, Johannesen J, Light G, Niznikiewicz M, Shapiro D, Woodberry K, Addington J, Bearden C, Cadenhead K, Cornblatt B, Perkins D, Stone W, Tsuang M, Walker E, Woods S, Cannon T, Mathalon D. 511. Associations of Cognitive Functions With EEG-Based Event-Related Potentials and Oscillations in Individuals at Clinical High-Risk for Psychosis: A Canonical Correlation Analysis of NAPLS2 Data. Biological Psychiatry 2025, 97: s308. DOI: 10.1016/j.biopsych.2025.02.750.Peer-Reviewed Original ResearchMismatch Negativity as a Predictor of Future Outcomes Among Individuals at Clinical High-Risk for Psychosis: Parsing Components of Auditory Predictive Coding in the North American Psychosis-Risk Longitudinal Study (NAPLS3) Sample
Hamilton H, Nicholas S, Hua J, Roach B, Belger A, Carrion R, Duncan E, Johannesen J, Keshavan M, Loo S, Niznikiewicz M, Light G, Billah T, Lavoie S, Whitford T, Addington J, Bearden C, Cadenhead K, Cannon T, Cornblatt B, Perkins D, Stone W, Tsuang M, Walker E, Woods S, Mathalon D, Schizophrenia A. Mismatch Negativity as a Predictor of Future Outcomes Among Individuals at Clinical High-Risk for Psychosis: Parsing Components of Auditory Predictive Coding in the North American Psychosis-Risk Longitudinal Study (NAPLS3) Sample. Biological Psychiatry 2025, 97: s69. DOI: 10.1016/j.biopsych.2025.02.180.Peer-Reviewed Original Research571. Preliminary Findings on the Association Between Psychotropic Medication and Symptom Profile Changes in Youth at Clinical High Risk for Psychosis
Zhou Q, Ananth A, Yuan E, Ku B, Goldsmith D, Addington J, Bearden C, Cadenhead K, Mukhtar H, Cannon T, Cornblatt B, Keshavan M, Mathalon D, Perkins D, Stone W, Woods S, Walker E. 571. Preliminary Findings on the Association Between Psychotropic Medication and Symptom Profile Changes in Youth at Clinical High Risk for Psychosis. Biological Psychiatry 2025, 97: s333-s334. DOI: 10.1016/j.biopsych.2025.02.810.Peer-Reviewed Original ResearchCannabis Use in Clinical High-Risk for Psychosis Across Different Legal Environments: Preliminary Findings From the Global Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) Study
Penzel N, Kelly S, Seitz-Holland J, Cho K, Corcoran C, Calkins M, Cornblatt B, Jacobs G, Kambeitz J, Lewandowski K, Mittal V, Polosecki P, Shah J, Coleman M, Bearden C, Kane J, Kahn R, McGorry P, Woods S, Shenton M, Nelson B, Pasternak O, Investigators A. Cannabis Use in Clinical High-Risk for Psychosis Across Different Legal Environments: Preliminary Findings From the Global Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) Study. Biological Psychiatry 2025, 97: s34-s35. DOI: 10.1016/j.biopsych.2025.02.099.Peer-Reviewed Original ResearchHigh rates of suicidality and parasuicidal behavior in individuals at clinical high-risk for psychosis: Implications for suicide risk assessment and suicide prevention
Trujillo T, Mirzakhanian H, Addington J, Bearden C, Cannon T, Cornblatt B, Keshavan M, Mathalon D, Perkins D, Stone W, Walker E, Woods S, Cadenhead K. High rates of suicidality and parasuicidal behavior in individuals at clinical high-risk for psychosis: Implications for suicide risk assessment and suicide prevention. Schizophrenia Research 2025, 281: 1-9. PMID: 40300257, DOI: 10.1016/j.schres.2025.04.030.Peer-Reviewed Original ResearchConceptsClinical high riskCalgary Depression Scale for SchizophreniaClinical high-risk youthSuicide risk assessmentParasuicidal behaviorSuicidal ideationLife eventsSelf-harmNorth American Prodrome Longitudinal StudyClinical high-risk participantsStructured Assessment of Violence RiskAssessment of Violence RiskClinical high-risk groupHealthy controlsRates of suicidal ideationHistory of self-harmHistory of SILevels of suicidalityStressful life eventsPredictors of SIRates of suicideAssociated with worse symptomsCHR participantsPsychotic conversionDSM diagnoses
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