2024
Microglia-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 symptomsAnhedonia
2023
Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments
Krystal J, Kaye A, Jefferson S, Girgenti M, Wilkinson S, Sanacora G, Esterlis I. Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2305772120. PMID: 38011560, PMCID: PMC10710048, DOI: 10.1073/pnas.2305772120.Peer-Reviewed Original ResearchA pilot randomized controlled trial of ketamine in Borderline Personality Disorder
Fineberg S, Choi E, Shapiro-Thompson R, Dhaliwal K, Neustadter E, Sakheim M, Null K, Trujillo-Diaz D, Rondeau J, Pittaro G, Peters J, Corlett P, Krystal J. A pilot randomized controlled trial of ketamine in Borderline Personality Disorder. Neuropsychopharmacology 2023, 48: 991-999. PMID: 36804489, PMCID: PMC10209175, DOI: 10.1038/s41386-023-01540-4.Peer-Reviewed Original ResearchConceptsBorderline personality disorderSecondary outcome measuresOutcome measuresSocio-occupational functioningSuicidal ideationPilot studyTrial of ketaminePersonality disorderInfusion of ketaminePrimary outcome measureEffects of ketamineMidazolam groupAdverse eventsKetamine groupClinical benefitMood symptomsKetamineFDA approvalDrug midazolamInfusionBPD symptomsLarger studyDepressed moodSymptomsChronic mood
2022
COVID-19 Traumatic Disaster Appraisal and Stress Symptoms Among Health Care Workers
Olson K, Fogelman N, Maturo L, Alvarado J, Ball S, Forray A, Hu M, Ivy M, Kapo J, Krystal J, Mayes L, Rohrbaugh R, Southwick S, Tebes J, Wassel B, Sinha R. COVID-19 Traumatic Disaster Appraisal and Stress Symptoms Among Health Care Workers. Journal Of Occupational And Environmental Medicine 2022, 64: 934-941. PMID: 35959912, PMCID: PMC9640251, DOI: 10.1097/jom.0000000000002673.Peer-Reviewed Original ResearchConceptsHealth care workersCare workersChronic mental healthCross-sectional evaluationTotal Worker HealthAdverse psychological outcomesPredictive factorsSevere stress eventsResponse rateCare qualityMental healthAdverse effectsPrivate practitionersHigh levelsWorkers' healthSense of controlStress symptomsPsychological outcomesLevel of educationGreater proportionHealthPandemicStress eventsSymptomsWorkersCorrection to: Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial
Abdallah CG, Roache JD, Gueorguieva R, Averill LA, Young-McCaughan S, Shiroma PR, Purohit P, Brundige A, Murff W, Ahn KH, Sherif MA, Baltutis EJ, Ranganathan M, D’Souza D, Martini B, Southwick SM, Petrakis IL, Burson RR, Guthmiller KB, López-Roca AL, Lautenschlager KA, McCallin JP, Hoch MB, Timchenko A, Souza SE, Bryant CE, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH. Correction to: Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Neuropsychopharmacology 2022, 47: 1583-1584. PMID: 35545665, PMCID: PMC9205895, DOI: 10.1038/s41386-022-01339-9.Peer-Reviewed Original Research
2021
Potential Schizophrenia Medications Point to New Disease Model
Krystal J. Potential Schizophrenia Medications Point to New Disease Model. Psychiatric News 2021, 56 DOI: 10.1176/appi.pn.2021.11.37.Peer-Reviewed Original ResearchSubthreshold post-traumatic stress disorder as a risk factor for post-traumatic stress disorder: results from a sample of USA veterans
Pietrzak RH, Javier FG, Krystal JH, Southwick SM. Subthreshold post-traumatic stress disorder as a risk factor for post-traumatic stress disorder: results from a sample of USA veterans. The British Journal Of Psychiatry 2021, 219: 456-459. PMID: 35048836, DOI: 10.1192/bjp.2021.17.Peer-Reviewed Original ResearchConceptsSubthreshold post-traumatic stress disorderPost-traumatic stress disorderStress disorderRisk factorsProspective national cohortPotential risk factorsLow dispositional optimismSpecific PTSD symptomsTrauma-exposed veteransNational cohortAssociated FactorsPreventive interventionsPTSD symptomsVeteransDisordersGreater ageCognitive difficultiesWave 1Dispositional optimismCohortSymptomsFactorsTrauma
2020
Dopamine and glutamate in schizophrenia: biology, symptoms and treatment
McCutcheon RA, Krystal JH, Howes OD. Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry 2020, 19: 15-33. PMID: 31922684, PMCID: PMC6953551, DOI: 10.1002/wps.20693.Peer-Reviewed Original ResearchDopamine systemAberrant dopamine signallingStriatal dopamine synthesisNovel pharmacological therapiesPathophysiology of schizophreniaEnvironmental risk factorsPharmacological therapyGlutamatergic dysfunctionDopaminergic functionRisk factorsGlutamate systemDopamine synthesisGenetic risk variantsPreclinical studiesPsychotic symptomsDopamine functionNew treatmentsNeural circuitsDopamine signalingNeuronal signalingSchizophreniaConsistent findingRisk variantsSymptomsGlutamate
2019
Lower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterationsAssociation of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder
Yoon G, Petrakis IL, Krystal JH. Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder. JAMA Psychiatry 2019, 76: 337-338. PMID: 30624551, PMCID: PMC6439824, DOI: 10.1001/jamapsychiatry.2018.3990.Peer-Reviewed Original ResearchKetamine: A Paradigm Shift for Depression Research and Treatment
Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS. Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron 2019, 101: 774-778. PMID: 30844397, PMCID: PMC6560624, DOI: 10.1016/j.neuron.2019.02.005.Peer-Reviewed Original ResearchNeural computations of threat in the aftermath of combat trauma
Homan P, Levy I, Feltham E, Gordon C, Hu J, Li J, Pietrzak RH, Southwick S, Krystal JH, Harpaz-Rotem I, Schiller D. Neural computations of threat in the aftermath of combat trauma. Nature Neuroscience 2019, 22: 470-476. PMID: 30664770, PMCID: PMC6829910, DOI: 10.1038/s41593-018-0315-x.Peer-Reviewed Original ResearchConceptsPTSD symptomsPost-traumatic stress disorder symptomsHigher PTSD symptom severityThreat-predictive cuesPTSD symptom severityAssociative threatPredictive cuesNeural trackingDisorder symptomsPrediction errorCombat veteransDynamic learning rateNegative outcomesCombat traumaSmaller amygdala volumesNeural computationLatent markersSymptomatic veteransSymptom severityAmygdala volumeAssociabilityCuesLearning rateVeteransSymptoms
2018
BDNF Val66Met polymorphism and posttraumatic stress symptoms in U.S. military veterans: Protective effect of physical exercise
Pitts BL, Whealin JM, Harpaz-Rotem I, Duman RS, Krystal JH, Southwick SM, Pietrzak RH. BDNF Val66Met polymorphism and posttraumatic stress symptoms in U.S. military veterans: Protective effect of physical exercise. Psychoneuroendocrinology 2018, 100: 198-202. PMID: 30388593, DOI: 10.1016/j.psyneuen.2018.10.011.Peer-Reviewed Original ResearchMeSH KeywordsAgedAmino Acid SubstitutionBrain-Derived Neurotrophic FactorCase-Control StudiesExerciseFemaleHumansMaleMethionineMiddle AgedMilitary PersonnelPolymorphism, Single NucleotideProtective FactorsResilience, PsychologicalSeverity of Illness IndexStress Disorders, Post-TraumaticUnited StatesValineVeteransConceptsMet allele carriersBDNF Val66Met polymorphismAllele carriersVal66Met polymorphismPhysical exerciseGreater severityPTSD symptomsU.S. military veteransTrauma burdenBrain-derived neurotrophic factor (BDNF) Val66Met polymorphismPast-month PTSD symptomsNeurotrophic factor Val66Met polymorphismMilitary veteransLifetime trauma burdenHigh trauma burdenVal/ValAdrenal (HPA) axis reactivityPosttraumatic stress disorder (PTSD) symptomsBDNF releaseCurrent PTSD symptomsProtective effectRe-experiencing symptomsAxis reactivityPosttraumatic stress symptomsSymptoms2. MICROCIRCUITS, MACROCIRCUITS, AND CORTICOL DYSFUNCTION IN SCHIZOPHRENIA: A COMPUTATIONAL AND TRANSLATIONAL NEUROSCIENCE PERSPECTIVE
Krystal J. 2. MICROCIRCUITS, MACROCIRCUITS, AND CORTICOL DYSFUNCTION IN SCHIZOPHRENIA: A COMPUTATIONAL AND TRANSLATIONAL NEUROSCIENCE PERSPECTIVE. Schizophrenia Bulletin 2018, 44: s1-s1. PMCID: PMC5887654, DOI: 10.1093/schbul/sby014.001.Peer-Reviewed Original ResearchNMDA glutamate receptorsNMDA receptor antagonistCortical functional connectivityPathophysiology of schizophreniaReceptor antagonistTranslational neuroscience perspectiveGlutamate receptorsHealthy humansAnimal modelsSchizophrenia patientsMemory impairmentNeuropsychiatric disordersSynaptic signalingFunctional connectivityNovel therapeuticsSchizophreniaDisordersPresentationPatientsPathophysiologyDysfunctionKetamineAntagonistSymptomsAbnormalities
2017
Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in U.S. military veterans: Results from the National Health and Resilience in Veterans Study
Mota NP, Han S, Harpaz‐Rotem I, Maruff P, Krystal JH, Southwick SM, Gelernter J, Pietrzak RH. Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in U.S. military veterans: Results from the National Health and Resilience in Veterans Study. Depression And Anxiety 2017, 35: 168-177. PMID: 29172227, PMCID: PMC5794529, DOI: 10.1002/da.22698.Peer-Reviewed Original ResearchConceptsΕ4 allele carriersApolipoprotein E gene polymorphismE gene polymorphismTrauma burdenU.S. military veteransAllele carriersPosttraumatic stress disorderPTSD symptomsNational HealthGreater social supportGene polymorphismsGreater severityMilitary veteransVeterans StudyAPOE ε4 carrier statusSocial supportΕ4 carrier statusAPOE genotypeΕ4 noncarriersPosttraumatic stress symptomsIndependent replication sampleSymptomsPTSD riskStress disorderCarrier statusSynaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic
Krystal JH, Abdallah CG, Averill LA, Kelmendi B, Harpaz-Rotem I, Sanacora G, Southwick SM, Duman RS. Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic. Current Psychiatry Reports 2017, 19: 74. PMID: 28844076, PMCID: PMC5904792, DOI: 10.1007/s11920-017-0829-z.Peer-Reviewed Original ResearchConceptsSynaptic connectivityRapid-acting treatmentPathophysiology of PTSDPotential clinical importanceTreatment of PTSDSynaptic lossPurpose of ReviewStudiesDisconnection syndromeClinical importanceNovel pharmacotherapeuticsNovel therapeuticsPTSD symptomsRecent FindingsHerePTSDPathophysiologyKetamineTreatmentDisordersTherapeutic applicationsStress-related lossesSyndromeSymptomsPharmacotherapeutics
2016
PTSD: from neurobiology to pharmacological treatments
Kelmendi B, Adams TG, Yarnell S, Southwick S, Abdallah CG, Krystal JH. PTSD: from neurobiology to pharmacological treatments. European Journal Of Psychotraumatology 2016, 7: 31858. PMID: 27837583, PMCID: PMC5106865, DOI: 10.3402/ejpt.v7.31858.Peer-Reviewed Original ResearchPosttraumatic stress disorderPharmacological treatmentPathophysiology of PTSDFirst-line pharmacotherapyMultiple neurobiological systemsEtiology of PTSDFull remissionTherapeutic effectPsychiatric disordersPharmacologic targetStress disorderNeurobiological systemsPathophysiologyFuture targetsTreatmentTraumatic eventsDisordersRemissionPharmacotherapyEtiologyInjurySymptomsYearsWeeksThe Role of GluN2C-Containing NMDA Receptors in Ketamine's Psychotogenic Action and in Schizophrenia Models
Khlestova E, Johnson JW, Krystal JH, Lisman J. The Role of GluN2C-Containing NMDA Receptors in Ketamine's Psychotogenic Action and in Schizophrenia Models. Journal Of Neuroscience 2016, 36: 11151-11157. PMID: 27807157, PMCID: PMC5148234, DOI: 10.1523/jneurosci.1203-16.2016.Peer-Reviewed Original ResearchConceptsNMDAR antagonistsNMDA receptor hypofunction hypothesisDifferent NMDAR subtypesHealthy human subjectsSymptoms of schizophreniaPsychotogenic effectsNMDA receptorsNMDAR subtypesSchizophrenia modelKetamine's abilityNegative symptomsKetamineMultiple subtypesPsychotic statesPreferential involvementSchizophreniaAntagonistGluN2CSubtypesReceptorsEEG powerHuman subjectsNMDARSymptomsΔ oscillationsLate-life exacerbation of PTSD symptoms in US veterans: results from the National Health and Resilience in Veterans Study.
Mota N, Tsai J, Kirwin PD, Harpaz-Rotem I, Krystal JH, Southwick SM, Pietrzak RH. Late-life exacerbation of PTSD symptoms in US veterans: results from the National Health and Resilience in Veterans Study. The Journal Of Clinical Psychiatry 2016, 77: 348-54. PMID: 27046308, DOI: 10.4088/jcp.15m10101.Peer-Reviewed Original ResearchConceptsOlder US veteransPosttraumatic stress disorderUS veteransPTSD symptomsNational HealthVeterans StudyMultivariable logistic regression modelWorst traumaDelayed-onset posttraumatic stress disorderExecutive dysfunctionWave 2Population-based dataUS military veteransLogistic regression modelsWave 1Cohort studySignificant exacerbationGreater severitySymptomsOlder ageStress disorderSelf-reported cognitive difficultiesPotential targetMilitary veteransLater life
2014
Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia
Xu K, Krystal JH, Ning Y, Chen da C, He H, Wang D, Ke X, Zhang X, Ding Y, Liu Y, Gueorguieva R, Wang Z, Limoncelli D, Pietrzak RH, Petrakis IL, Zhang X, Fan N. Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia. Journal Of Psychiatric Research 2014, 61: 64-72. PMID: 25560772, PMCID: PMC4445679, DOI: 10.1016/j.jpsychires.2014.12.012.Peer-Reviewed Original ResearchConceptsKetamine groupNegative Syndrome ScaleSchizophrenia groupSyndrome ScaleN-methyl-D-aspartate (NMDA) glutamate receptor antagonistGlutamate receptor antagonistsPotential confounding factorsEarly course schizophreniaSymptom dimensionsSymptoms of schizophreniaReceptor antagonistChronic schizophreniaHealthy subjectsKetamine abuseSchizophrenia psychosisSchizophrenia patientsConfounding factorsSymptom severitySymptomsInpatientsSchizophreniaPsychosisKetamine usersDissociation symptomsPrincipal component factor analysis