2024
Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression
Swanberg K, Prinsen H, Averill C, Campos L, Kurada A, Krystal J, Petrakis I, Averill L, Rothman D, Abdallah C, Juchem C. Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression. NMR In Biomedicine 2024, 37: e5220. PMID: 39054694, DOI: 10.1002/nbm.5220.Peer-Reviewed Original ResearchPosttraumatic stress disorderMedial prefrontal cortexStress disorderPosttraumatic stress disorder patientsPosttraumatic stress disorder diagnosisChronic psychiatric conditionImpact of psychiatric comorbiditiesComorbid MDDPrefrontal cortexDepressive disorderTraumatic stressorsPsychiatric conditionsMDDPsychiatric comorbiditiesNeurotransmitter abnormalitiesConcentrations of glutamateMetabolite abnormalitiesHealthy controlsDisordersPattern of abnormalitiesParticipantsGlutamateIn vivo protonMetabolic abnormalitiesDepressionFindings of PTSD-specific deficits in default mode network strength following a mild experimental stressor
Averill C, Averill L, Akiki T, Fouda S, Krystal J, Abdallah C. Findings of PTSD-specific deficits in default mode network strength following a mild experimental stressor. NPP—Digital Psychiatry And Neuroscience 2024, 2: 9. PMID: 38919723, PMCID: PMC11197271, DOI: 10.1038/s44277-024-00011-y.Peer-Reviewed Original ResearchPosttraumatic stress disorderMajor depressive disorderConnectivity deficitsConnection strengthPrimary diagnosis of posttraumatic stress disorderExperimental stressorsDiagnosis of posttraumatic stress disorderResting-state functional magnetic resonance imagingFunctional magnetic resonance imagingVentromedial prefrontal cortexDMN connectivity strengthStress-induced reductionEffect of groupDMN alterationsPrefrontal cortexDepressive disorderDMN connectivityStressor taskStress disorderBrain region(sAcute stressorFunctional connectivityDMNExploratory analysisDeficits
2023
Neural 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 ResearchConceptsPosttraumatic 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
Abnormal glutamate metabolism in prefrontal cortex of post-traumatic stress disorder linked to comorbidity with major depression
Swanberg K, Prinsen H, Averill C, Campos L, Kurada A, Krystal J, Petrakis I, Averill L, Abdallah C, Juchem C. Abnormal glutamate metabolism in prefrontal cortex of post-traumatic stress disorder linked to comorbidity with major depression. Proceedings Of The International Society For Magnetic Resonance In Medicine ... Scientific Meeting And Exhibition. 2022 DOI: 10.58530/2022/3344.Peer-Reviewed Original ResearchReward 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 ResearchConceptsMemory 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
2019
Regulation of Craving and Negative Emotion in Alcohol Use Disorder
Suzuki S, Mell MM, O'Malley SS, Krystal JH, Anticevic A, Kober H. Regulation of Craving and Negative Emotion in Alcohol Use Disorder. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2019, 5: 239-250. PMID: 31892465, PMCID: PMC7010564, DOI: 10.1016/j.bpsc.2019.10.005.Peer-Reviewed Original ResearchConceptsAlcohol use disorderNegative emotionsNegative affectPrefrontal cortexIndividual differencesRegulation conditionsCognitive behavioral therapy treatmentEmotion regulation taskFunctional magnetic resonance imagingNegative affect conditionRegulation of cravingNegative alcohol expectanciesNotable individual differencesSelf-reported cravingBehavioral therapy treatmentUse disordersRegulation successCognitive strategiesAffect conditionRegulation strategiesAlcohol expectanciesPFC regionsNeural mechanismsRegulation taskAUD treatmentA multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms
Fleming LM, Javitt DC, Carter CS, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman J, Krystal JH, Corlett PR. A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms. NeuroImage Clinical 2019, 22: 101739. PMID: 30852397, PMCID: PMC6411494, DOI: 10.1016/j.nicl.2019.101739.Peer-Reviewed Original ResearchConceptsDorsolateral prefrontal cortexN-methyl-D-aspartate (NMDA) glutamate receptor antagonistFunctional connectivityKetamine-induced alterationsGlutamate receptor antagonistsAltered brain functionState functional connectivityRsfMRI connectivityRisk patientsMulticenter studyKetamine effectsReceptor antagonistDLPFC connectivityMimic symptomsHealthy individualsKetamine usePositive symptomsCertain biomarkersBrain functionPrefrontal cortexPatientsConnectivity signaturesSeed-based measuresSchizophreniaKetamine
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 studyCerebellar and Prefrontal Cortical Alterations in PTSD: Structural and Functional Evidence
Holmes SE, Scheinost D, DellaGioia N, Davis MT, Matuskey D, Pietrzak RH, Hampson M, Krystal JH, Esterlis I. Cerebellar and Prefrontal Cortical Alterations in PTSD: Structural and Functional Evidence. Chronic Stress 2018, 2: 2470547018786390. PMID: 30035247, PMCID: PMC6054445, DOI: 10.1177/2470547018786390.Peer-Reviewed Original ResearchPosttraumatic stress disorderIntrinsic connectivity distributionMedial prefrontal cortexTensor-based morphometryPTSD groupFunctional connectivityPrefrontal cortexPathophysiology of PTSDGray matter volumeWhole-brain connectivityKey brain regionsMiddle temporal gyrusDorsolateral prefrontal cortexDefault mode networkCentral executive networkFunctional connectivity analysisPFC alterationsCortical alterationsHealthy comparison participantsAltered volumeFunctional alterationsMatter volumeUnmedicated individualsCerebellar involvementBrain regions
2017
Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD
Wrocklage KM, Averill LA, Scott J, Averill CL, Schweinsburg B, Trejo M, Roy A, Weisser V, Kelly C, Martini B, Harpaz-Rotem I, Southwick SM, Krystal JH, Abdallah CG. Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD. European Neuropsychopharmacology 2017, 27: 515-525. PMID: 28279623, PMCID: PMC5429865, DOI: 10.1016/j.euroneuro.2017.02.010.Peer-Reviewed Original ResearchConceptsClinician-Administered PTSD ScalePTSD symptom dimensionsPTSD diagnosisCombat exposureCortical thicknessSymptom dimensionsMagnetic resonance imagingPosttraumatic stress disorder (PTSD) symptomsU.S. veteransCortical thinningUnique brain regionsLeft lateral prefrontalAnxious arousalPTSD dimensionsNeural correlatesHigh-resolution magnetic resonance imagingCortical thickness reductionsLateral prefrontalPTSD symptomsDisorder symptomsCombat severityCurrent PTSDPTSD ScalePrefrontal cortexPotential confoundsAnterior 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 disorderKETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah CG, Adams TG, Kelmendi B, Esterlis I, Sanacora G, Krystal JH. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS. Depression And Anxiety 2016, 33: 689-697. PMID: 27062302, PMCID: PMC4961540, DOI: 10.1002/da.22501.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAntidepressant effectsKetamine's mechanismN-methyl-D-aspartate receptor antagonistRapid-acting antidepressant effectsPrefrontal cortexSingle subanesthetic doseRapid antidepressant effectsTreatment-resistant depressionFull therapeutic effectEfficacy of ketamineKetamine's antidepressant effectsRapid acting antidepressantsFuture clinical prospectsGlutamate surgeTraditional antidepressantsAntidepressant medicationCascade of eventsReceptor antagonistSubanesthetic doseDepressive disorderClinical dataTherapeutic effectTreatment responseLimited efficacy
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
In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5
DeLorenzo C, DellaGioia N, Bloch M, Sanacora G, Nabulsi N, Abdallah C, Yang J, Wen R, Mann JJ, Krystal JH, Parsey RV, Carson RE, Esterlis I. In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5. Biological Psychiatry 2014, 77: 266-275. PMID: 25156701, PMCID: PMC4277907, DOI: 10.1016/j.biopsych.2014.06.024.Peer-Reviewed Original ResearchConceptsSubtype 5Ketamine administrationPET scansMetabotropic glutamate receptor subtype 5Prefrontal cortexAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced effectsPositron emission tomography (PET) ligandGlutamate receptor antagonistsVolume of distributionMedial prefrontal cortexNegative allosteric modulatorsKetamine initiationGlutamate releaseDorsal putamenKetamine responseSubanesthetic dosesOrbital prefrontal cortexReceptor antagonistAcute effectsBolus injectionDorsal caudateArterial bloodScan 1
2013
Global Resting-State Functional Magnetic Resonance Imaging Analysis Identifies Frontal Cortex, Striatal, and Cerebellar Dysconnectivity in Obsessive-Compulsive Disorder
Anticevic A, Hu S, Zhang S, Savic A, Billingslea E, Wasylink S, Repovs G, Cole MW, Bednarski S, Krystal JH, Bloch MH, Li CS, Pittenger C. Global Resting-State Functional Magnetic Resonance Imaging Analysis Identifies Frontal Cortex, Striatal, and Cerebellar Dysconnectivity in Obsessive-Compulsive Disorder. Biological Psychiatry 2013, 75: 595-605. PMID: 24314349, PMCID: PMC3969771, DOI: 10.1016/j.biopsych.2013.10.021.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderPrefrontal cortexResting-state functional connectivity dataStriatum/nucleus accumbensVentral striatum/nucleus accumbensResting-state functional connectivity studiesVentral anterior cingulate cortexCortico-striatal circuitsMagnetic Resonance Imaging AnalysisAnterior cingulate cortexFunctional connectivity studiesBasal gangliaControl subjectsFunctional connectivity dataAnterior thalamusRight putamenFrontal cortexNucleus accumbensDorsal striatumCerebellar cortexAbnormal neural connectivityCerebellar dysconnectivityCingulate cortexWhole brainFunctional magnetic resonance imaging (fMRI) analysisCharacterizing Thalamo-Cortical Disturbances in Schizophrenia and Bipolar Illness
Anticevic A, Cole MW, Repovs G, Murray JD, Brumbaugh MS, Winkler AM, Savic A, Krystal JH, Pearlson GD, Glahn DC. Characterizing Thalamo-Cortical Disturbances in Schizophrenia and Bipolar Illness. Cerebral Cortex 2013, 24: 3116-3130. PMID: 23825317, PMCID: PMC4224238, DOI: 10.1093/cercor/bht165.Peer-Reviewed Original ResearchConceptsThalamo-cortical systemThalamic connectivityBipolar illnessResting-state functional magnetic resonance imagingSensory-motor cortexSevere mental illnessFunctional magnetic resonance imagingMagnetic resonance imagingThalamic dysconnectivityThalamic seedsClinical presentationNeuropsychiatric syndromeBrain dysconnectivityThalamic nucleiBipolar patientsSchizophrenia patientsSensory gatingMental illnessResonance imagingDysconnectivityCerebellar regionsDiagnostic membershipPrefrontal cortexSchizophreniaIllness
2012
Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of Disinhibition Associated with Schizophrenia in a Cortical Working Memory Model
Murray JD, Anticevic A, Gancsos M, Ichinose M, Corlett PR, Krystal JH, Wang XJ. Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of Disinhibition Associated with Schizophrenia in a Cortical Working Memory Model. Cerebral Cortex 2012, 24: 859-872. PMID: 23203979, PMCID: PMC3948492, DOI: 10.1093/cercor/bhs370.Peer-Reviewed Original ResearchConceptsWorking memoryNeural levelSpatial WM taskWorking Memory ModelSpatial working memoryPersistent activity patternsWM representationsWM taskWM maintenanceBrain mechanismsWM deficitsMicrocircuit dysfunctionPrefrontal cortexCognitive deficitsBehavioral dataMemory modelBehavioral variabilityWM deteriorationCognitive impairmentCortical disinhibitionExcitation-inhibition balanceMain model predictionsDisinhibitionBehavioral deficitsDeficitsDifferential brain response to alcohol cue distractors across stages of alcohol dependence
Fryer SL, Jorgensen KW, Yetter EJ, Daurignac EC, Watson TD, Shanbhag H, Krystal JH, Mathalon DH. Differential brain response to alcohol cue distractors across stages of alcohol dependence. Biological Psychology 2012, 92: 282-291. PMID: 23131612, PMCID: PMC3947923, DOI: 10.1016/j.biopsycho.2012.10.004.Peer-Reviewed Original ResearchConceptsAnterior cingulate cortexAlcohol cuesBrain responsesLong-term abstainersAlcohol dependenceDorsal anterior cingulate cortexRecruitment of attentionVentral anterior cingulate cortexCognitive control regionsAlcohol-related cuesCue-reactivity studiesCue-related activationsNon-alcohol cuesAttention-demanding taskDifferential brain responsesTarget detection taskInferior parietal lobuleMedial prefrontal cortexAlcohol-dependent individualsCue exposureAltered attentionDistractor effectNeural responsesParietal lobulePrefrontal cortex