2023
Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex
Rompala G, Nagamatsu S, Martínez-Magaña J, Nuñez-Ríos D, Wang J, Girgenti M, Krystal J, Gelernter J, Hurd Y, Montalvo-Ortiz J. Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex. Nature Communications 2023, 14: 4544. PMID: 37507366, PMCID: PMC10382503, DOI: 10.1038/s41467-023-40285-y.Peer-Reviewed Original ResearchMeSH Keywords5-MethylcytosineAnalgesics, OpioidDNA MethylationEpigenesis, GeneticEpigenomeHumansMaleNeuronsOpioid-Related DisordersPrefrontal CortexConceptsOpioid use disorderMulti-omics findingsGene expression patternsCo-methylation analysisGene expression profilesMulti-omics profilingGene networksDNA methylationNeuronal methylomesDNA hydroxymethylationMethylomic analysisExpression patternsExpression profilesEpigenetic disturbancesUse disordersPsychiatric traitsOrbitofrontal cortexOpioid-related drugsPostmortem orbitofrontal cortexEnvironmental factorsDrug interaction analysisOUD treatmentHuman orbitofrontal cortexOpioid signalingInteraction analysisNeural valuation of rewards and punishments in posttraumatic stress disorder: a computational approach
Jia R, Ruderman L, Pietrzak R, Gordon C, Ehrlich D, Horvath M, Mirchandani S, DeFontes C, Southwick S, Krystal J, Harpaz-Rotem I, Levy I. Neural valuation of rewards and punishments in posttraumatic stress disorder: a computational approach. Translational Psychiatry 2023, 13: 101. PMID: 36977676, PMCID: PMC10050320, DOI: 10.1038/s41398-023-02388-4.Peer-Reviewed Original ResearchMeSH KeywordsBrain MappingFearHumansMagnetic Resonance ImagingMalePrefrontal CortexPunishmentRewardStress Disorders, Post-TraumaticConceptsPosttraumatic stress disorderValuation systemStress disorderCombat veteransMaintenance of PTSDSubjective valueBrain valuation systemNeural valuation systemVentromedial prefrontal cortexFunctional MRI studyFunction of symptomsMale combat veteransNeural valuationSeries of choicesFear learningPunishment processingPosttrauma symptomsPTSD symptomsNeural encodingNeural mechanismsUncertain optionsPrefrontal cortexSubjective valuationVentral striatumMonetary gains
2022
Reward and loss incentives improve spatial working memory by shaping trial-by-trial posterior frontoparietal signals
Cho YT, Moujaes F, Schleifer CH, Starc M, Ji JL, Santamauro N, Adkinson B, Kolobaric A, Flynn M, Krystal JH, Murray JD, Repovs G, Anticevic A. Reward and loss incentives improve spatial working memory by shaping trial-by-trial posterior frontoparietal signals. NeuroImage 2022, 254: 119139. PMID: 35346841, PMCID: PMC9264479, DOI: 10.1016/j.neuroimage.2022.119139.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain MappingHumansMagnetic Resonance ImagingMemory, Short-TermMotivationParietal LobePrefrontal CortexRewardConceptsMemory precisionSpatial working memoryIntraparietal sulcusPrecentral sulcusWorking memoryMotivational signalsBOLD signalParietal cortexReward/lossVisual association regionsDorsolateral prefrontal cortexGoal-directed activityMemory paradigmMemory performanceMemory processesAnterior parietal cortexExecutive networkNeural changesSensory processesPrefrontal cortexLoss incentivesVentral striatumNon-human primate studiesTranslational neuroscienceMemory
2020
Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder
Stone LA, Girgenti MJ, Wang J, Ji D, Zhao H, Krystal JH, Duman R. Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder. The International Journal Of Neuropsychopharmacology 2020, 24: 118-129. PMID: 32951025, PMCID: PMC8611677, DOI: 10.1093/ijnp/pyaa072.Peer-Reviewed Original ResearchConceptsUpstream regulatorGene co-expression network analysisCo-expression network analysisFunctional genomic studiesPutative upstream regulatorsIngenuity Pathway Analysis softwarePathway Analysis softwarePathway annotationGenomic studiesTranscriptomic modulesTranscriptomic dataTranscriptomic alterationsGene expressionDrinking and responses to antidrinking messages among young adults: An fMRI study
Garrison KA, DeMartini KS, Corlett PR, Worhunsky PD, Krystal JH, O'Malley SS. Drinking and responses to antidrinking messages among young adults: An fMRI study. Addiction Biology 2020, 26: e12882. PMID: 32068323, PMCID: PMC7431375, DOI: 10.1111/adb.12882.Peer-Reviewed Original ResearchConceptsDrinking cuesNeural responsesYoung adultsFunctional magnetic resonanceSelf-reported drinkingPast monthNeutral cuesDrug cuesSmoking cuesHabitual responsesReward processingFMRI studyDrinking quantityCuesDependent individualsSubstance useAlcohol useBinge drinkingNegative consequencesGreater baselinePublic health campaignsExcessive drinkingHeavy drinkingHealth campaignsDrinking
2018
The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects
Abdallah CG, De Feyter HM, Averill LA, Jiang L, Averill CL, Chowdhury GMI, Purohit P, de Graaf RA, Esterlis I, Juchem C, Pittman BP, Krystal JH, Rothman DL, Sanacora G, Mason GF. The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology 2018, 43: 2154-2160. PMID: 29977074, PMCID: PMC6098048, DOI: 10.1038/s41386-018-0136-3.Peer-Reviewed Original ResearchConceptsGlutamate-glutamine cyclingGlutamate neurotransmissionAntidepressant effectsKetamine effectsRodent studiesN-methyl-D-aspartate receptor antagonistRapid antidepressant effectsClinician-Administered Dissociative States ScaleEffects of ketamineGlutamine enrichmentKetamine infusionGlutamate releaseKetamine administrationSubanesthetic dosesPsychotomimetic effectsReceptor antagonistNormal salineSchizophrenia pathophysiologyFrontal cortexMRS scansDepressed subjectsKetamineNeurotransmissionPrefrontal cortexPilot studyDefault mode network abnormalities in posttraumatic stress disorder: A novel network-restricted topology approach
Akiki TJ, Averill CL, Wrocklage KM, Scott JC, Averill LA, Schweinsburg B, Alexander-Bloch A, Martini B, Southwick SM, Krystal JH, Abdallah CG. Default mode network abnormalities in posttraumatic stress disorder: A novel network-restricted topology approach. NeuroImage 2018, 176: 489-498. PMID: 29730491, PMCID: PMC5976548, DOI: 10.1016/j.neuroimage.2018.05.005.Peer-Reviewed Original Research
2017
Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder
Scheinost D, Holmes SE, DellaGioia N, Schleifer C, Matuskey D, Abdallah CG, Hampson M, Krystal JH, Anticevic A, Esterlis I. Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder. Neuropsychopharmacology 2017, 43: 1119-1127. PMID: 28944772, PMCID: PMC5854800, DOI: 10.1038/npp.2017.229.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAnterior cingulate cortexIntrinsic functional connectivityMedial prefrontal cortexFunctional connectivityLarge-scale brain networksDepressive disorderMDD groupAnatomical covarianceBrain networksUnmedicated major depressive disorderWhole-brain intrinsic functional connectivitySystem-level disorderIntrinsic connectivity distributionRegional brain structureMultiple brain networksAltered connectivityCommon findingHealthy comparison participantsDepressive symptomsAltered volumeUnmedicated individualsLocal circuitryCingulate cortexDepressive symptomatologyAnterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach
Abdallah CG, Wrocklage KM, Averill CL, Akiki T, Schweinsburg B, Roy A, Martini B, Southwick SM, Krystal JH, Scott JC. Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach. Translational Psychiatry 2017, 7: e1045-e1045. PMID: 28244983, PMCID: PMC5545643, DOI: 10.1038/tp.2017.12.Peer-Reviewed Original ResearchConceptsGlobal brain connectivityPosttraumatic stress disorderAnterior hippocampusStress disorderPTSD severityTraumatic brain injuryMultimodal approachOverall PTSD severityAnxiety-related behaviorDorsolateral prefrontal connectivityDorsolateral prefrontal cortexElevated PTSD symptomsAnatomical dysconnectivityHippocampal dysconnectivityUS veteransBrain injuryHippocampal volumePTSD subgroupBrain biomarkersClinical valueMedication statusPrefrontal connectivitySignificant associationPrefrontal cortexBrain connectivity
2016
Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder
Murrough JW, Abdallah CG, Anticevic A, Collins KA, Geha P, Averill LA, Schwartz J, DeWilde KE, Averill C, Jia-Wei Yang G, Wong E, Tang CY, Krystal JH, Iosifescu DV, Charney DS. Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder. Human Brain Mapping 2016, 37: 3214-3223. PMID: 27144347, PMCID: PMC4980239, DOI: 10.1002/hbm.23235.Peer-Reviewed Original ResearchConceptsGlobal brain connectivityMedial prefrontal cortexPrefrontal cortexRight subgenual anterior cingulate cortexVentromedial prefrontal cortexCingulate cortexMontgomery-Åsberg Depression Rating ScaleSymptom severityBrain connectivitySubgenual anterior cingulate cortexDepression Rating ScaleMedication-free patientsMajor depressive disorderKey pathological featureDepressive symptom severitySubgenual cingulate cortexHum Brain MappAnterior cingulate cortexHigher symptom severityFunctional connectivity analysisFunctional magnetic resonancePathological featuresHealthy groupAltered connectivityDepressive disorder
2015
Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress
Licznerski P, Duric V, Banasr M, Alavian KN, Ota KT, Kang HJ, Jonas EA, Ursano R, Krystal JH, Duman RS, . Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress. PLOS Biology 2015, 13: e1002282. PMID: 26506154, PMCID: PMC4623974, DOI: 10.1371/journal.pbio.1002282.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBehavior, AnimalCohort StudiesDendritic SpinesDepressive Disorder, MajorEnzyme RepressionFemaleGene Transfer TechniquesHippocampusHumansImmediate-Early ProteinsMaleMiddle AgedNerve Tissue ProteinsNeuronsPrefrontal CortexProtein Serine-Threonine KinasesRats, Sprague-DawleySignal TransductionStress Disorders, Post-TraumaticSynaptic TransmissionTissue BanksConceptsMajor depressive disorderPost-traumatic stress disorderPrefrontal cortexAbnormal dendritic spine morphologyCorticolimbic brain regionsAnhedonic-like behaviorInhibition of SGK1Dendritic spine morphologyKinase 1 expressionAmygdala of individualsTraumatic stressPostmortem prefrontal cortexSynaptic dysfunctionDepressive disorderBehavioral deficitsRodent modelsPTSD subjectsFunctional alterationsBrain regionsSGK1 expressionSpine morphologyStress disorderFunction contributesBehavioral changesDisordersEarly-Course Unmedicated Schizophrenia Patients Exhibit Elevated Prefrontal Connectivity Associated with Longitudinal Change
Anticevic A, Hu X, Xiao Y, Hu J, Li F, Bi F, Cole MW, Savic A, Yang GJ, Repovs G, Murray JD, Wang XJ, Huang X, Lui S, Krystal JH, Gong Q. Early-Course Unmedicated Schizophrenia Patients Exhibit Elevated Prefrontal Connectivity Associated with Longitudinal Change. Journal Of Neuroscience 2015, 35: 267-286. PMID: 25568120, PMCID: PMC4287147, DOI: 10.1523/jneurosci.2310-14.2015.Peer-Reviewed Original ResearchConceptsEarly course schizophreniaFunctional connectivityPrefrontal cortexImmediate symptom improvementSevere mental illnessEarly course patientsHealthy human subjectsHuman subjectsWhole-brain levelFunctional connectivity patternsResting-state fMRIIllness onsetSymptom improvementChronic illnessFunctional impairmentTherapeutic implicationsPFC connectivityOverall connection strengthMental illnessLongitudinal progressionLongitudinal changesSchizophrenia studiesSchizophreniaDiagnostic classificationPatients
2014
Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics
Abdallah CG, Sanacora G, Duman RS, Krystal JH. Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics. Annual Review Of Medicine 2014, 66: 1-15. PMID: 25341010, PMCID: PMC4428310, DOI: 10.1146/annurev-med-053013-062946.Peer-Reviewed Original ResearchConceptsRapid antidepressant effectsAntidepressant effectsGlutamate-based antidepressantsTolerability of ketamineRapid-acting antidepressantsTreatment-resistant depressionNeurobiology of depressionPotent antidepressant effectsRapid acting antidepressantsBiology of depressionPotential treatment targetHours of treatmentTreatment targetsKetamineAntidepressantsBiomarker studiesDepressionNeurobiologyTolerabilityN-Methyl-D-Aspartate Receptor Antagonist Effects on Prefrontal Cortical Connectivity Better Model Early Than Chronic Schizophrenia
Anticevic A, Corlett PR, Cole MW, Savic A, Gancsos M, Tang Y, Repovs G, Murray JD, Driesen NR, Morgan PT, Xu K, Wang F, Krystal JH. N-Methyl-D-Aspartate Receptor Antagonist Effects on Prefrontal Cortical Connectivity Better Model Early Than Chronic Schizophrenia. Biological Psychiatry 2014, 77: 569-580. PMID: 25281999, DOI: 10.1016/j.biopsych.2014.07.022.Peer-Reviewed Original ResearchMeSH KeywordsAdultChronic DiseaseExcitatory Amino Acid AntagonistsFemaleHumansKetamineMaleNeural PathwaysPrefrontal CortexSchizophreniaYoung AdultConceptsHealthy volunteersFunctional connectivityKetamine effectsChronic schizophreniaIllness progressionChronic illnessHigh riskRecent pharmacologic studiesReceptor antagonist effectsAspartate glutamate receptorsStages of schizophreniaCourse of schizophreniaGlutamate dysfunctionPharmacologic modelsPrefrontal cortex functionIllness stageNMDAR antagonistsFunctional dysconnectivityGlutamate receptorsPharmacologic studiesHealthy subjectsSchizophrenia onsetFunctional alterationsDevelopment of therapeuticsAntagonist effectsVentral Anterior Cingulate Connectivity Distinguished Nonpsychotic Bipolar Illness From Psychotic Bipolar Disorder and Schizophrenia
Anticevic A, Savic A, Repovs G, Yang G, McKay DR, Sprooten E, Knowles EE, Krystal JH, Pearlson GD, Glahn DC. Ventral Anterior Cingulate Connectivity Distinguished Nonpsychotic Bipolar Illness From Psychotic Bipolar Disorder and Schizophrenia. Schizophrenia Bulletin 2014, 41: 133-143. PMID: 24782562, PMCID: PMC4266289, DOI: 10.1093/schbul/sbu051.Peer-Reviewed Original ResearchConceptsVentral anterior cingulate cortexBipolar illnessPsychosis historyWhole-brain connectivityBipolar patientsConnectivity alterationsBrain connectivityCo-occurring psychosisChronic schizophrenia patientsHealthy comparison subjectsBipolar disorder patientsPsychotic bipolar disorder patientsBipolar disorder groupAnterior cingulate cortexFunctional connectivity studiesPsychotic bipolar disorderLifetime psychosisChronic schizophreniaPsychotic symptomsDisorder patientsPatientsComparison subjectsSchizophrenia patientsBipolar disorderCingulate cortex
2013
Amygdala Connectivity Differs Among Chronic, Early Course, and Individuals at Risk for Developing Schizophrenia
Anticevic A, Tang Y, Cho YT, Repovs G, Cole MW, Savic A, Wang F, Krystal JH, Xu K. Amygdala Connectivity Differs Among Chronic, Early Course, and Individuals at Risk for Developing Schizophrenia. Schizophrenia Bulletin 2013, 40: 1105-1116. PMID: 24366718, PMCID: PMC4133672, DOI: 10.1093/schbul/sbt165.Peer-Reviewed Original ResearchConceptsHealthy comparison subjectsAmygdala connectivityHigh riskSymptom severityOrbitofrontal cortexWhole-brain functional connectivityHR individualsResting-state connectivitySchizophrenia symptom severityFunctional magnetic resonanceAmygdala seedArousal nucleiInitial episodeSchizophrenia neuropathologyChronic schizophreniaBrainstem regionsIllness phasePsychosis onsetElevated riskAmygdala circuitsEarly courseComparison subjectsFunctional alterationsClinical groupsFunctional connectivityThe Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity
Driesen NR, McCarthy G, Bhagwagar Z, Bloch MH, Calhoun VD, D'Souza DC, Gueorguieva R, He G, Leung HC, Ramani R, Anticevic A, Suckow RF, Morgan PT, Krystal JH. The Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity. Neuropsychopharmacology 2013, 38: 2613-2622. PMID: 23856634, PMCID: PMC3828532, DOI: 10.1038/npp.2013.170.Peer-Reviewed Original ResearchConceptsNMDA-Rs
2012
Global Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History
Anticevic A, Brumbaugh MS, Winkler AM, Lombardo LE, Barrett J, Corlett PR, Kober H, Gruber J, Repovs G, Cole MW, Krystal JH, Pearlson GD, Glahn DC. Global Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History. Biological Psychiatry 2012, 73: 565-573. PMID: 22980587, PMCID: PMC3549314, DOI: 10.1016/j.biopsych.2012.07.031.Peer-Reviewed Original ResearchConceptsPsychosis historyRisk factorsBipolar patientsSymptom severityResting-state functional magnetic resonanceAmygdala-mPFC connectivityFronto-limbic dysfunctionSevere clinical courseBipolar I patientsEmotion regulation regionsPsychotic symptom severityFunctional magnetic resonanceClinical courseI patientsLimbic structuresBipolar illnessConnectivity deficitsAmygdala findingsConnectivity abnormalitiesPathophysiological modelBipolar IPatientsBipolar disorderDysconnectivityAbnormal inhibitionA broken filter: Prefrontal functional connectivity abnormalities in schizophrenia during working memory interference
Anticevic A, Repovs G, Krystal JH, Barch DM. A broken filter: Prefrontal functional connectivity abnormalities in schizophrenia during working memory interference. Schizophrenia Research 2012, 141: 8-14. PMID: 22863548, PMCID: PMC3879404, DOI: 10.1016/j.schres.2012.07.007.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceBrain MappingFemaleFunctional LateralityHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMemory DisordersMemory, Short-TermMiddle AgedNerve NetNeural PathwaysNeuropsychological TestsOxygenPrefrontal CortexSchizophreniaSchizophrenic PsychologyConceptsFunctional connectivity abnormalitiesConnectivity abnormalitiesMedio-dorsal thalamusTask-based functional connectivityFinal common pathwayMaintenance phasePrefrontal cortical regionsDorsolateral prefrontal cortex activationPrefrontal cortex activationFunctional deficitsHealthy controlsSub-cortical regionsExtended amygdalaPatientsCortex activationCognitive deficitsCortical regionsFunctional connectivityLife outcomesAbnormalitiesDLPFC networkCommon pathwaySchizophrenia researchSchizophreniaMemory abnormalities
2010
Working Memory Overload: Fronto-Limbic Interactions and Effects on Subsequent Working Memory Function
Yun RJ, Krystal JH, Mathalon DH. Working Memory Overload: Fronto-Limbic Interactions and Effects on Subsequent Working Memory Function. Brain Imaging And Behavior 2010, 4: 96-108. PMID: 20503117, PMCID: PMC2854358, DOI: 10.1007/s11682-010-9089-9.Peer-Reviewed Original ResearchConceptsMemory systemAmygdala-prefrontal interactionsSubsequent cognitive performanceWorking Memory FunctionFunctional magnetic resonanceDorsolateral prefrontal cortexMemory taskCognitive functioningNegative affectAmygdala activationCognitive performanceTask performanceCognitive overloadNeural effectsPrefrontal cortexMemory functionPerformance accuracySubsequent functioningSeparate factorsBrain regionsPerformance declineReduced activationFunctioningInverse couplingOverload effect