2024
Human brain state dynamics are highly reproducible and associated with neural and behavioral features
Lee K, Ji J, Fonteneau C, Berkovitch L, Rahmati M, Pan L, Repovš G, Krystal J, Murray J, Anticevic A. Human brain state dynamics are highly reproducible and associated with neural and behavioral features. PLOS Biology 2024, 22: e3002808. PMID: 39316635, PMCID: PMC11421804, DOI: 10.1371/journal.pbio.3002808.Peer-Reviewed Original ResearchConceptsCo-activation patternsResting-state functional magnetic resonance imagingFunctional magnetic resonance imagingBehavioral featuresNeural variationsMoment-to-moment changesSingle-subject levelBrain state dynamicsEmotion regulationHealthy young adultsBehavioral phenotypesCognitive functionSubstance useNeural activityNeuroimaging markersNeural featuresYoung adultsMagnetic resonance imagingCo-activationResonance imagingCo-variationNeuroimagingIndividualsEmotionsFunctional outcomesMicroglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedoniaKetamine induces multiple individually distinct whole-brain functional connectivity signatures
Moujaes F, Ji J, Rahmati M, Burt J, Schleifer C, Adkinson B, Savic A, Santamauro N, Tamayo Z, Diehl C, Kolobaric A, Flynn M, Rieser N, Fonteneau C, Camarro T, Xu J, Cho Y, Repovs G, Fineberg S, Morgan P, Seifritz E, Vollenweider F, Krystal J, Murray J, Preller K, Anticevic A. Ketamine induces multiple individually distinct whole-brain functional connectivity signatures. ELife 2024, 13: e84173. PMID: 38629811, PMCID: PMC11023699, DOI: 10.7554/elife.84173.Peer-Reviewed Original ResearchConceptsResponse to ketamineAcute ketamineBehavioral effectsQuantified resting-state functional connectivityEffects of acute ketamineSymptom variationResting-state functional connectivityTreatment-resistant depressionFunctional connectivity signaturesGlobal brain connectivitySingle-subject levelInter-individual variabilityPlacebo-controlled studyFunctional connectivityConnectivity signaturesBrain connectivityHealthy participantsSingle-blind placebo-controlled studyNeural variationsTreatment conditionsKetamineGene expression targetsPharmacological biomarkersPilot awardParvalbumin
2023
Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium
Zhu X, Kim Y, Ravid O, He X, Suarez-Jimenez B, Zilcha-Mano S, Lazarov A, Lee S, Abdallah C, Angstadt M, Averill C, Baird C, Baugh L, Blackford J, Bomyea J, Bruce S, Bryant R, Cao Z, Choi K, Cisler J, Cotton A, Daniels J, Davenport N, Davidson R, DeBellis M, Dennis E, Densmore M, deRoon-Cassini T, Disner S, Hage W, Etkin A, Fani N, Fercho K, Fitzgerald J, Forster G, Frijling J, Geuze E, Gonenc A, Gordon E, Gruber S, Grupe D, Guenette J, Haswell C, Herringa R, Herzog J, Hofmann D, Hosseini B, Hudson A, Huggins A, Ipser J, Jahanshad N, Jia-Richards M, Jovanovic T, Kaufman M, Kennis M, King A, Kinzel P, Koch S, Koerte I, Koopowitz S, Korgaonkar M, Krystal J, Lanius R, Larson C, Lebois L, Li G, Liberzon I, Lu G, Luo Y, Magnotta V, Manthey A, Maron-Katz A, May G, McLaughlin K, Mueller S, Nawijn L, Nelson S, Neufeld R, Nitschke J, O'Leary E, Olatunji B, Olff M, Peverill M, Phan K, Qi R, Quidé Y, Rektor I, Ressler K, Riha P, Ross M, Rosso I, Salminen L, Sambrook K, Schmahl C, Shenton M, Sheridan M, Shih C, Sicorello M, Sierk A, Simmons A, Simons R, Simons J, Sponheim S, Stein M, Stein D, Stevens J, Straube T, Sun D, Théberge J, Thompson P, Thomopoulos S, van der Wee N, van der Werff S, van Erp T, van Rooij S, van Zuiden M, Varkevisser T, Veltman D, Vermeiren R, Walter H, Wang L, Wang X, Weis C, Winternitz S, Xie H, Zhu Y, Wall M, Neria Y, Morey R. Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium. NeuroImage 2023, 283: 120412. PMID: 37858907, PMCID: PMC10842116, DOI: 10.1016/j.neuroimage.2023.120412.Peer-Reviewed Original ResearchFunctional brain networks reflect spatial and temporal autocorrelation
Shinn M, Hu A, Turner L, Noble S, Preller K, Ji J, Moujaes F, Achard S, Scheinost D, Constable R, Krystal J, Vollenweider F, Lee D, Anticevic A, Bullmore E, Murray J. Functional brain networks reflect spatial and temporal autocorrelation. Nature Neuroscience 2023, 26: 867-878. PMID: 37095399, DOI: 10.1038/s41593-023-01299-3.Peer-Reviewed Original Research
2022
Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder
Smart K, Worhunsky PD, Scheinost D, Angarita GA, Esterlis I, Carson RE, Krystal JH, O'Malley SS, Cosgrove KP, Hillmer AT. Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder. Alcohol Clinical And Experimental Research 2022, 46: 770-782. PMID: 35342968, PMCID: PMC9117461, DOI: 10.1111/acer.14816.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsDefault mode networkFunctional magnetic resonance imagingReceptor availabilityPositron emission tomographyAUD groupFunctional connectivityReceptor positron emission tomographyResting-state functional magnetic resonance imagingNetwork-level functional connectivityBrain connectivityWeeks of abstinenceGlobal functional connectivityAlcohol use disorderMagnetic resonance imagingFMRI outcomesHealthy controlsSupervised abstinencePET resultsUse disordersSynaptic plasticityResonance imagingBrain regionsEmission tomographyOrbitofrontal cortexImaging the effect of ketamine on synaptic density (SV2A) in the living brain
Holmes SE, Finnema SJ, Naganawa M, DellaGioia N, Holden D, Fowles K, Davis M, Ropchan J, Emory P, Ye Y, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Imaging the effect of ketamine on synaptic density (SV2A) in the living brain. Molecular Psychiatry 2022, 27: 2273-2281. PMID: 35165397, PMCID: PMC9133063, DOI: 10.1038/s41380-022-01465-2.Peer-Reviewed Original ResearchConceptsKetamine's therapeutic effectsMajor depressive disorderTherapeutic effectPositron emission tomographyPosttraumatic stress disorderHealthy controlsSynaptic connectionsSynaptic vesicle protein 2APost-synaptic mechanismsEffects of ketamineDiscovery of ketamineNon-human primatesAntidepressant effectsDepressive disorderSingle administrationSynaptic densityPsychiatric disordersDepression severityKetamineEmission tomographyTerminal densityLiving brainStress disorderRobust reductionDissociative symptoms
2021
Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups
Clausen AN, Fercho KA, Monsour M, Disner S, Salminen L, Haswell CC, Rubright EC, Watts AA, Buckley MN, Maron-Katz A, Sierk A, Manthey A, Suarez-Jimenez B, Olatunji BO, Averill CL, Hofmann D, Veltman DJ, Olson EA, Li G, Forster GL, Walter H, Fitzgerald J, Théberge J, Simons JS, Bomyea JA, Frijling JL, Krystal JH, Baker JT, Phan KL, Ressler K, Han LKM, Nawijn L, Lebois LAM, Schmaal L, Densmore M, Shenton ME, van Zuiden M, Stein M, Fani N, Simons RM, Neufeld RWJ, Lanius R, van Rooij S, Koch SBJ, Bonomo S, Jovanovic T, deRoon-Cassini T, Ely TD, Magnotta VA, He X, Abdallah CG, Etkin A, Schmahl C, Larson C, Rosso IM, Blackford JU, Stevens JS, Daniels JK, Herzog J, Kaufman ML, Olff M, Davidson RJ, Sponheim SR, Mueller SC, Straube T, Zhu X, Neria Y, Baugh LA, Cole JH, Thompson PM, Morey RA. Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups. Brain And Behavior 2021, 12: e2413. PMID: 34907666, PMCID: PMC8785613, DOI: 10.1002/brb3.2413.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderEffects of PTSDBrain-PADBrain ageMale controlsOld maleStress disorderAge-related brain changesStructural magnetic resonance imagingBrain structural magnetic resonance imagingOlder age groupsMagnetic resonance imagingChronological ageSubset of controlsContext of PTSDControl subjectsBrain changesBrain agingFuture longitudinal researchTreatment approachesLinear mixed effects modelsAdult subjectsResonance imagingAge groupsPTSD assessmentImaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Hillmer AT, Rusowicz A, Nabulsi N, Matuskey D, Angarita GA, Najafzadeh S, Kapinos M, Southwick SM, Krystal JH, Carson RE, Huang Y, Cosgrove KP. Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1. Journal Of Clinical Investigation 2021, 131: e150452. PMID: 34651587, PMCID: PMC8516462, DOI: 10.1172/jci150452.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPositron emission tomographyVolume of distributionDehydrogenase type 1Trauma-exposed controlsPTSD groupTranslocator proteinType 1Veterans Affairs (VA) National CenterOverall PTSD severityBrain glucocorticoidBrain immuneMethodsSixteen individualsPeripheral cortisolMicroglial markersImmune suppressionTranslational Science AwardsCortisol levelsNIH National CenterTC groupCortisol regulationEmission tomographyStress disorderLower PTSD symptomsPTSD symptomsTranscriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD
Burt JB, Preller KH, Demirtas M, Ji JL, Krystal JH, Vollenweider FX, Anticevic A, Murray JD. Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD. ELife 2021, 10: e69320. PMID: 34313217, PMCID: PMC8315798, DOI: 10.7554/elife.69320.Peer-Reviewed Original ResearchConceptsLysergic acid diethylamideEffects of LSDSerotonin 2A receptorPharmacological neuroimagingNeuromodulatory effectsPharmacological responseFunctional alterationsBrain physiologyCircuit mechanismsFunctional connectivityNeural functionBrain structuresPsychoactive drugsAcid diethylamideFunctional topographyPrecision medicineNeural differencesNeuroimagingAltered statesReceptors
2020
Transdiagnostic, Connectome-Based Prediction of Memory Constructs Across Psychiatric Disorders
Barron DS, Gao S, Dadashkarimi J, Greene AS, Spann MN, Noble S, Lake EMR, Krystal JH, Constable RT, Scheinost D. Transdiagnostic, Connectome-Based Prediction of Memory Constructs Across Psychiatric Disorders. Cerebral Cortex 2020, 31: 2523-2533. PMID: 33345271, PMCID: PMC8023861, DOI: 10.1093/cercor/bhaa371.Peer-Reviewed Original ResearchConceptsMacroscale brain networksIndividual differencesBrain networksMemory deficitsFunctional connectivityAttention deficit hyper-activity disorderTask-based functional MRI dataLong-term memoryWhole-brain functional connectivityDiagnostic groupsWhole-brain patternsDefault mode networkFunctional MRI dataHuman Connectome ProjectPsychiatric disordersMemory constructsMemory performanceTransdiagnostic sampleBrain correlatesMode networkFunctional connectomeConnectome ProjectLimbic networkHealthy participantsMemoryLongitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence
Hillmer AT, Angarita GA, Esterlis I, Anderson JM, Nabulsi N, Lim K, Ropchan J, Carson RE, Krystal JH, Malley S, Cosgrove KP. Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence. Neuropsychopharmacology 2020, 46: 380-385. PMID: 32919411, PMCID: PMC7852514, DOI: 10.1038/s41386-020-00856-9.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsSmoking statusAlcohol abstinenceEarly abstinenceMGlu5 receptor negative allosteric modulatorReceptor negative allosteric modulatorChronic alcohol useCortical brain regionsAlcohol use disorderEmission Tomography ImagingPositron emission tomography (PET) imagingNegative allosteric modulatorsDSM-5 criteriaCue-induced reinstatementHealthy controlsPreclinical literatureGlutamate systemPreclinical modelsHuman evidenceReceptor drugsPET scansUse disordersHuman studiesReceptor availabilityStudy durationMapping Lithium in the Brain: New 3-Dimensional Methodology Reveals Regional Distribution in Euthymic Patients With Bipolar Disorder
Mason GF, Krystal JH. Mapping Lithium in the Brain: New 3-Dimensional Methodology Reveals Regional Distribution in Euthymic Patients With Bipolar Disorder. Biological Psychiatry 2020, 88: 367-368. PMID: 32792052, DOI: 10.1016/j.biopsych.2020.05.023.Peer-Reviewed Original ResearchPredictive Processing in Mental Illness: Hierarchical Circuitry for Perception and Trauma
Kaye AP, Krystal JH. Predictive Processing in Mental Illness: Hierarchical Circuitry for Perception and Trauma. Journal Of Psychopathology And Clinical Science 2020, 129: 629-632. PMID: 32757606, DOI: 10.1037/abn0000628.Peer-Reviewed Original ResearchConceptsTrauma-related disordersPredictive processingDisorders of perceptionNeural circuitsHigher-order predictionsAbnormal psychologyPrediction errorSensory stimuliPredictive codingHierarchical circuitryPrior beliefsNew sensory dataPerceptionBayesian processPsychiatric disordersPsychotic disordersHierarchical viewHierarchical organizationMental illnessSensory dataBeliefsDisordersFuture directionsComputational layerProcessingPTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imagingPsilocybin Induces Time-Dependent Changes in Global Functional Connectivity
Preller KH, Duerler P, Burt JB, Ji JL, Adkinson B, Stämpfli P, Seifritz E, Repovš G, Krystal JH, Murray JD, Anticevic A, Vollenweider FX. Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity. Biological Psychiatry 2020, 88: 197-207. PMID: 32111343, DOI: 10.1016/j.biopsych.2019.12.027.Peer-Reviewed Original ResearchConceptsFunctional connectivityBaseline connectivityResting-state functional connectivityGlobal functional connectivityBrain-wide connectivityHealthy human participantsPersonalized medicine approachPeak effectUse of psilocybinMechanism of actionSerotonin 2ATime-dependent mannerCrossover studyPredictive markerPsychedelic treatmentMedicine approachReceptor systemSensory regionsClinical contextTime pointsAssociative regionsDifferent test daysAdministrationTest dayTime-dependent changes
2019
Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium
Dennis EL, Disner SG, Fani N, Salminen LE, Logue M, Clarke EK, Haswell CC, Averill CL, Baugh LA, Bomyea J, Bruce SE, Cha J, Choi K, Davenport ND, Densmore M, du Plessis S, Forster GL, Frijling JL, Gonenc A, Gruber S, Grupe DW, Guenette JP, Hayes J, Hofmann D, Ipser J, Jovanovic T, Kelly S, Kennis M, Kinzel P, Koch SBJ, Koerte I, Koopowitz S, Korgaonkar M, Krystal J, Lebois LAM, Li G, Magnotta VA, Manthey A, May GJ, Menefee DS, Nawijn L, Nelson SM, Neufeld RWJ, Nitschke JB, O’Doherty D, Peverill M, Ressler KJ, Roos A, Sheridan MA, Sierk A, Simmons A, Simons RM, Simons JS, Stevens J, Suarez-Jimenez B, Sullivan DR, Théberge J, Tran JK, van den Heuvel L, van der Werff SJA, van Rooij SJH, van Zuiden M, Velez C, Verfaellie M, Vermeiren RRJM, Wade BSC, Wager T, Walter H, Winternitz S, Wolff J, York G, Zhu Y, Zhu X, Abdallah CG, Bryant R, Daniels JK, Davidson RJ, Fercho KA, Franz C, Geuze E, Gordon EM, Kaufman ML, Kremen WS, Lagopoulos J, Lanius RA, Lyons MJ, McCauley SR, McGlinchey R, McLaughlin KA, Milberg W, Neria Y, Olff M, Seedat S, Shenton M, Sponheim SR, Stein DJ, Stein MB, Straube T, Tate DF, van der Wee NJA, Veltman DJ, Wang L, Wilde EA, Thompson PM, Kochunov P, Jahanshad N, Morey RA. Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium. Molecular Psychiatry 2019, 26: 4315-4330. PMID: 31857689, PMCID: PMC7302988, DOI: 10.1038/s41380-019-0631-x.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderWhite matter organizationStress disorderFractional anisotropyWhite matter microstructural organizationCurrent alcohol abuseTraumatic brain injuryChildhood trauma exposureMulti-cohort analysisWhite matter metricsAltered structural connectivityLower fractional anisotropyMatter organizationPsychotropic medicationsComorbid depressionBrain injuryCorpus callosumRight hippocampusAlcohol abuseDiffusion MRINeurobiological vulnerabilityHippocampal networkTrauma exposureAge 18Small sample sizeSchizophrenia Exhibits Bi-directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits
Ji JL, Diehl C, Schleifer C, Tamminga CA, Keshavan MS, Sweeney JA, Clementz BA, Hill SK, Pearlson G, Yang G, Creatura G, Krystal JH, Repovs G, Murray J, Winkler A, Anticevic A. Schizophrenia Exhibits Bi-directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits. Cerebral Cortex 2019, 29: 4463-4487. PMID: 31157363, PMCID: PMC6917525, DOI: 10.1093/cercor/bhy306.Peer-Reviewed Original ResearchConceptsBrain-wide alterationsResting-state functional magnetic resonanceSensory-motor cortexFunctional magnetic resonanceNeural dysconnectivityPolysynaptic connectionsCortico-striatoFunctional disturbancesChronic patientsAssociation cortexFocal disruptionNeural effectsCerebellar circuitsPatientsDysconnectivityStriatal componentsSchizophreniaCortexSpecific alterationsHallmark featureCognitive performanceAlterationsFunctional pathwaysQuestion accountsMagnetic resonanceIn vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation
Davis MT, Hillmer A, Holmes SE, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Angarita G, Carson RE, Krystal JH, Esterlis I. In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 11490-11495. PMID: 31085640, PMCID: PMC6561298, DOI: 10.1073/pnas.1818871116.Peer-Reviewed Original ResearchConceptsMGluR5 availabilitySuicidal ideationHC individualsPathophysiology of PTSDLimbic brain regionsVolume of distributionHealthy comparison controlsSuicide risk managementPositron emission tomographyReceptor 5Venous input functionsBrain regionsPTSD individualsEmission tomographyMDD individualsVivo evidenceRecent evidencePotential roleMGluR5PTSDComparison controlsDysregulationMDDIdeationIndividualsAltered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments
Duman RS, Sanacora G, Krystal JH. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron 2019, 102: 75-90. PMID: 30946828, PMCID: PMC6450409, DOI: 10.1016/j.neuron.2019.03.013.Peer-Reviewed Original ResearchConceptsAltered connectivityDepressed patientsExcitatory glutamate neuronsMajor neuronal typesRapid-acting agentsAtrophy of neuronsTreatment of depressionLimbic brain regionsChronic stress exposureStress-related disordersBrain imaging studiesImportant sex differencesNeurotransmitter deficitsGABA interneuronsImmunologic mechanismsGlutamate neuronsCurrent antidepressantsExcitotoxic effectsNeurochemical deficitsGlutamate dysfunctionPathophysiological mechanismsGABA systemInflammatory cytokinesAdrenal glucocorticoidsHippocampal region