2024
Posttraumatic Stress Disorder, Obesity, and Accelerated Epigenetic Aging Among US Military Veterans
Fischer I, Na P, Nagamatsu S, Jeste D, Cabrera-Mendoza B, Montalvo-Ortiz J, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Posttraumatic Stress Disorder, Obesity, and Accelerated Epigenetic Aging Among US Military Veterans. JAMA Psychiatry 2024, 81 PMID: 39476130, PMCID: PMC11581715, DOI: 10.1001/jamapsychiatry.2024.3403.Peer-Reviewed Original ResearchDexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo‐controlled crossover laboratory study
Petrakis I, Nolen T, Vandergrift N, Hirsch S, Krystal J, De Vivo M, Sabados J, Pisani E, Newcomb J, Kosten T. Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo‐controlled crossover laboratory study. American Journal On Addictions 2024 PMID: 39152094, DOI: 10.1111/ajad.13637.Peer-Reviewed Original ResearchPathophysiology of posttraumatic stress disorderAlcohol use disorderSubjective effects of alcoholEffects of alcoholUse disorderComorbid alcohol use disorderAlcohol cue reactivityPosttraumatic stress disorderCrossover laboratory studyCue reactivityAlcohol cravingNoradrenergic dysregulationStress disorderBlood pressureSubjective effectsEthanol administrationClinically significant adverse effectsPharmacotherapeutic approachesTest daysReceptor agonistsPotential treatmentDouble-blind fashionCravingDrinking alcoholDisordersMedial 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 abnormalitiesDepressionThe Prefrontal Cortex Transcriptomic Landscape of the Comorbidity Between Post-Traumatic Stress Disorder and Opioid Misuse
Martinez-Magaña J, Nagamatsu S, Nunez-Rios D, Krystal J, Girgenti M, Group T, Montalvo-Ortiz J. The Prefrontal Cortex Transcriptomic Landscape of the Comorbidity Between Post-Traumatic Stress Disorder and Opioid Misuse. Biological Psychiatry 2024, 95: s69. DOI: 10.1016/j.biopsych.2024.02.169.Peer-Reviewed Original ResearchRecent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023
Havlik J, Wahid S, Teopiz K, McIntyre R, Krystal J, Rhee T. Recent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023. Current Psychiatry Reports 2024, 26: 176-213. PMID: 38386251, DOI: 10.1007/s11920-024-01494-4.Peer-Reviewed Original ResearchTreatment of treatment-resistant depressionTreatment-resistant depressionMedication discontinuation ratesTranscranial magnetic stimulationElectroconvulsive therapyPsychiatric approachApproach to treatmentAdjunctive pharmacotherapyIntervention approachesAdjunctive treatmentDiscontinuation ratesMagnetic stimulationGeneralizability resultsDepressionPharmacotherapyInclusion criteriaAntipsychoticsPsychotherapyNarrative reviewKetamine/esketamineSide effectsStudy inclusion criteriaRecent FindingsRecent evidenceDisordersBuprenorphine
2023
Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms
Krystal J, Kavalali E, Monteggia L. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology 2023, 49: 41-50. PMID: 37488280, PMCID: PMC10700627, DOI: 10.1038/s41386-023-01629-w.Peer-Reviewed Original ResearchConceptsMood disordersEffective treatmentN-methyl-D-aspartate receptorsGlutamatergic N-methyl-D-aspartate receptorRapid antidepressant effectsTreatment-resistant depressionKey clinical aspectsRapid antidepressant actionsNovel effective treatmentsSynaptic signaling mechanismsMore effective treatmentsSynaptic plasticity mechanismsOpen channel blockerAntidepressant actionAntidepressant effectsKetamine effectsChannel blockersClinical aspectsClinical practiceNew treatmentsNeuropsychiatric disordersCircuit mechanismsDisordersTreatmentKetamine511. Common and Distinct Effects of Incentives on Spatial Working Memory in Schizophrenia and Obsessive-Compulsive Disorder
Sarantopoulos C, Shin D, Schleifer C, Moujaes F, Adkinson B, Ji J, Kolabaric A, Flynn M, Santamauro N, Krystal J, Murray J, Repovs G, Martin W, Pittenger C, Anticevic A, Cho Y. 511. Common and Distinct Effects of Incentives on Spatial Working Memory in Schizophrenia and Obsessive-Compulsive Disorder. Biological Psychiatry 2023, 93: s300-s301. DOI: 10.1016/j.biopsych.2023.02.751.Peer-Reviewed Original Research
2022
Post-traumatic Stress Disorder
Merians A, Spiller T, Harpaz-Rotem I, Krystal J, Pietrzak R. Post-traumatic Stress Disorder. Medical Clinics Of North America 2022, 107: 85-99. PMID: 36402502, DOI: 10.1016/j.mcna.2022.04.003.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderStress disorderCognitive processing therapyCognitive behavioral therapyEye movement desensitizationEvidence-based psychotherapiesTraumatic eventsBehavioral therapyNegative alterationsFirst-line pharmacologic treatmentStructured interviewsFirst-line treatmentNonpsychiatric settingsLarge bodyPharmacologic treatmentReuptake inhibitorsCognitionDisordersArousalTherapeutic interventionsMoodPsychotherapyAvoidanceTherapyInterventionAbnormal 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 Research
2021
Subthreshold 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
Multivariate genome-wide analysis of education, socioeconomic status and brain phenome
Wendt FR, Pathak GA, Lencz T, Krystal JH, Gelernter J, Polimanti R. Multivariate genome-wide analysis of education, socioeconomic status and brain phenome. Nature Human Behaviour 2020, 5: 482-496. PMID: 33349686, PMCID: PMC8068566, DOI: 10.1038/s41562-020-00980-y.Peer-Reviewed Original ResearchConceptsPsychosocial factorsSocioeconomic statusPsychiatric disordersBipolar disorderGenetic riskNeuronal cell typesMajor depressionTourette syndromeBrain morphologyDisordersImaging phenotypesCell typesRisky behaviorsPsychopathologyGenetic overlapRiskGenetic discoveriesPsychiatric traitsStatusSyndromePredictive 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 layerProcessing
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 evidenceSymptomsDepressionSeverityDisordersAlterations
2018
The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder
Abdallah CG, Averill LA, Akiki TJ, Raza M, Averill CL, Gomaa H, Adikey A, Krystal JH. The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder. The Annual Review Of Pharmacology And Toxicology 2018, 59: 171-189. PMID: 30216745, PMCID: PMC6326888, DOI: 10.1146/annurev-pharmtox-010818-021701.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStress disorderTreatment of PTSDBiology of PTSDExert complex effectsBrain functionNeurobiologySynaptic gainPathology modelRapid-acting antidepressantsBroader frameworkDisordersWordsPutative mechanismsDysconnectivitySynaptic lossPharmacotherapeutic optionsClinical efficacyCompelling efficacyPerspectiveAntidepressantsDrug developmentComplex effectsPathologyEfficacy2. 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
Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia
Logue MW, van Rooij SJH, Dennis EL, Davis SL, Hayes JP, Stevens JS, Densmore M, Haswell CC, Ipser J, Koch SBJ, Korgaonkar M, Lebois LAM, Peverill M, Baker JT, Boedhoe PSW, Frijling JL, Gruber SA, Harpaz-Rotem I, Jahanshad N, Koopowitz S, Levy I, Nawijn L, O’Connor L, Olff M, Salat DH, Sheridan MA, Spielberg JM, van Zuiden M, Winternitz SR, Wolff JD, Wolf EJ, Wang X, Wrocklage K, Abdallah CG, Bryant RA, Geuze E, Jovanovic T, Kaufman ML, King AP, Krystal JH, Lagopoulos J, Bennett M, Lanius R, Liberzon I, McGlinchey RE, McLaughlin KA, Milberg WP, Miller MW, Ressler KJ, Veltman DJ, Stein DJ, Thomaes K, Thompson PM, Morey RA. Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia. Biological Psychiatry 2017, 83: 244-253. PMID: 29217296, PMCID: PMC5951719, DOI: 10.1016/j.biopsych.2017.09.006.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStress disorderTrauma-exposed control subjectsCurrent posttraumatic stress disorderSmaller hippocampal volumesControl subjectsSmaller hippocampiHippocampal volumeClinical dataAmygdala volumeAmygdala findingsSmaller amygdalaConsortium studySubcortical structuresNeuroimaging studiesLargest neuroimaging studyENIGMA consortiumBrain responsesNeurobiological underpinningsPsychiatric Genomics ConsortiumDisordersSubjectsWorking GroupSignificance levelHippocampusSynaptic 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 lossesSyndromeSymptomsPharmacotherapeuticsAltered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence
Holmes SE, Girgenti MJ, Davis MT, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Southwick S, Duman RS, Carson RE, Krystal JH, Esterlis I, Friedman M, Kowall N, Brady C, McKee A, Stein T, Huber B, Kaloupek D, Alvarez V, Benedek D, Ursano R, Williamson D, Cruz D, Young K, Duman R, Krystal J, Mash D, Hardegree M, Serlin G. Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 8390-8395. PMID: 28716937, PMCID: PMC5547601, DOI: 10.1073/pnas.1701749114.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMGluR5 availabilityPositron emission tomographyGlutamate systemMetabotropic glutamate receptor 5Treatment of PTSDHuman posttraumatic stress disorderGlutamate receptor 5Mechanism-based treatmentsExpression of FKBP5Promising treatment targetHuman postmortem tissueTargeted pharmacological treatmentStress psychopathologyPharmacological treatmentExpression of proteinsReceptor 5MGluR5Treatment targetsPostmortem tissueEmission tomographyStress disorderPostmortem samplesPromising targetDisordersMoral injury in U.S. combat veterans: Results from the national health and resilience in veterans study
Wisco BE, Marx BP, May CL, Martini B, Krystal JH, Southwick SM, Pietrzak RH. Moral injury in U.S. combat veterans: Results from the national health and resilience in veterans study. Depression And Anxiety 2017, 34: 340-347. PMID: 28370818, DOI: 10.1002/da.22614.Peer-Reviewed Original ResearchMental disordersNational HealthCombat veteransU.S. combat veteransCurrent mental disorderPast psychiatric disordersPopulation-based sampleCombat severityMental health problemsMoral Injury Events ScaleFunctional outcomeMoral injuryWhite racePsychiatric disordersHealth problemsU.S. veteransSuicidal ideationVeterans StudySuicide attemptsInjurious eventsCombat exposureSociodemographic variablesDisordersExposure historyVeteransSearching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders
Foss-Feig JH, Adkinson BD, Ji JL, Yang G, Srihari VH, McPartland JC, Krystal JH, Murray JD, Anticevic A. Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders. Biological Psychiatry 2017, 81: 848-861. PMID: 28434615, PMCID: PMC5436134, DOI: 10.1016/j.biopsych.2017.03.005.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSpectrum disorderFunctional magnetic resonance imagingRecent theoretical accountsEarly course schizophreniaNeurodevelopmental disordersPharmacological challenge studiesNeural correlatesNeuroscience literatureTheoretical accountsNeural circuitryTheoretical neuroscienceNoninvasive neuroimagingBehavioral dysfunctionFuture researchNeuropsychiatric conditionsComputational modelSchizophreniaProton magnetic resonance spectroscopyDisordersInhibition imbalanceMagnetic resonance imagingDistinct modalitiesPoint of convergenceInhibition balance