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 gainsPsychometric Properties of the Self-Injurious Thoughts and Behaviors Interview–Short Form Among U.S. Active Duty Military Service Members and Veterans
Stanley I, Marx B, Fina B, Young-McCaughan S, Tyler H, Sloan D, Blankenship A, Dondanville K, Walker J, Boffa J, Bryan C, Brown L, Straud C, Mintz J, Abdallah C, Back S, Blount T, DeBeer B, Flanagan J, Foa E, Fox P, Fredman S, Krystal J, McDevitt-Murphy M, McGeary D, Pruiksma K, Resick P, Roache J, Shiroma P, Taylor D, Wachen J, Kaplan A, López-Roca A, Nicholson K, Schobitz R, Schrader C, Sharrieff A, Yarvis J, Litz B, Keane T, Peterson A. Psychometric Properties of the Self-Injurious Thoughts and Behaviors Interview–Short Form Among U.S. Active Duty Military Service Members and Veterans. Assessment 2023, 30: 2332-2346. PMID: 36644835, DOI: 10.1177/10731911221143979.Peer-Reviewed Original ResearchConceptsBehaviors Interview-Short FormPosttraumatic stress disorderSelf-injurious thoughtsMilitary service membersService membersDiscriminant validitySelf-report measuresInterview-based measuresSuicidal ideationSelf-report questionnairesActive duty military service membersSuicide-related thoughtsActive duty service membersPTSD symptomsStress disorderRelated constructsGood convergentConvergent validityResponse formatPsychometric propertiesSuicide risk assessmentInterrater reliabilityHigh interrater reliabilityIdeationVeterans
2022
Polygenic scores for empathy associate with posttraumatic stress severity in response to certain traumatic events
Wendt FR, Warrier V, Pathak GA, Koenen KC, Stein MB, Krystal JH, Pietrzak RH, Gelernter J, Goldfarb EV, Baron-Cohen S, Polimanti R. Polygenic scores for empathy associate with posttraumatic stress severity in response to certain traumatic events. Neurobiology Of Stress 2022, 17: 100439. PMID: 35242894, PMCID: PMC8881478, DOI: 10.1016/j.ynstr.2022.100439.Peer-Reviewed Original ResearchPosttraumatic stress disorderTraumatic eventsPolygenic scoringGreater emotional sensitivityChildhood neglect/abusePTSD symptom severityCertain traumatic eventsSevere PTSD symptomsPosttraumatic stress severityContext of traumaNeglect/abuseEarly life adversityHigher empathyPTSD symptomsEmotional sensitivityHigh empathizersStress disorderLife eventsEmpathyPotential traumaSymptom severityPolygenic scoresAutismStress severityDepressionDose-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. 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: 1574-1581. PMID: 35046508, PMCID: PMC8767037, DOI: 10.1038/s41386-022-01266-9.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderClinical trialsOutcome measuresMontgomery-Åsberg Depression Rating ScaleSelf-report PTSD ChecklistÅsberg Depression Rating ScaleStress disorderPTSD symptomsAntidepressant-resistant symptomsPrevious antidepressant treatmentClinician-Administered PTSD ScaleMulti-center clinical trialRapid antidepressant effectsSecondary outcome measuresPrimary outcome measureSignificant dose-related effectsRole of ketamineDepression Rating ScaleDose-related effectsEffects of ketamineDSM-5Intravenous placeboDose ketamineTreatment discontinuationActive duty military
2021
Imaging 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 symptomsAttachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study
Tamman AJF, Wendt FR, Pathak GA, Krystal JH, Southwick SM, Sippel LM, Gelernter J, Polimanti R, Pietrzak RH. Attachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study. Biological Psychiatry 2021, 91: 637-646. PMID: 34955171, DOI: 10.1016/j.biopsych.2021.09.025.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderAttachment styleU.S. military veteransIncident posttraumatic stress disorderSocial environmental factorsDevelopment of PTSDMilitary veteransInsecure attachment stylesSecure attachment stylePolygenic riskEffect of PRSLifetime trauma burdenPTSD preventionPosttraumatic stressPTSD developmentPTSD symptomsStress disorderPolygenic risk scoresHigh polygenic riskProspective designNationally RepresentativePotential pharmacotherapyMultivariate geneStyleVeteransSubthreshold 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
2019
Neural 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 symptomsSymptoms
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 lossesSyndromeSymptomsPharmacotherapeuticsCortical 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 confoundsThe Association of PTSD Symptom Severity With Localized Hippocampus and Amygdala Abnormalities
Akiki TJ, Averill CL, Wrocklage KM, Schweinsburg B, Scott JC, Martini B, Averill LA, Southwick SM, Krystal JH, Abdallah CG. The Association of PTSD Symptom Severity With Localized Hippocampus and Amygdala Abnormalities. Chronic Stress 2017, 1: 2470547017724069. PMID: 28825050, PMCID: PMC5562232, DOI: 10.1177/2470547017724069.Peer-Reviewed Original ResearchPosttraumatic stress disorderUS veteransAmygdala abnormalitiesVertex-wise shape analysisPTSD symptomsClinician-Administered PTSD ScaleCross-sectional studyHigh-resolution magnetic resonanceStructural neuroimaging studiesSevere PTSD symptomsHippocampal abnormalitiesPTSD symptom severitySubtle morphometric changesRe-experiencing symptomsRight hippocampusCentromedial amygdalaPTSD symptom clustersRight amygdalaPTSD ScaleAnterior hippocampusHippocampusStructural abnormalitiesDSM-IVSymptom clustersSymptom severity
2016
Probable Posttraumatic Stress Disorder in the US Veteran Population According to DSM-5: Results From the National Health and Resilience in Veterans Study.
Wisco BE, Marx BP, Miller MW, Wolf EJ, Mota NP, Krystal JH, Southwick SM, Pietrzak RH. Probable Posttraumatic Stress Disorder in the US Veteran Population According to DSM-5: Results From the National Health and Resilience in Veterans Study. The Journal Of Clinical Psychiatry 2016, 77: 1503-1510. PMID: 27631148, DOI: 10.4088/jcp.15m10188.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAfghan Campaign 2001-AgedCohort StudiesCombat DisordersComorbidityCross-Sectional StudiesDiagnostic and Statistical Manual of Mental DisordersFemaleFollow-Up StudiesHealth SurveysHumansIraq War, 2003-2011Life Change EventsMaleMental DisordersMiddle AgedResilience, PsychologicalStress Disorders, Post-TraumaticSurveys and QuestionnairesVeteransYoung AdultConceptsProbable posttraumatic stress disorderDSM-5 posttraumatic stress disorderPosttraumatic stress disorderUS veteran populationPsychiatric comorbidityUS veteransNational HealthVeteran populationVeterans StudyStress disorderPTSD symptomsOdds of moodHigh public health burdenPublic health burdenPopulation-based samplePast-month prevalenceDSM-5Specific PTSD symptomsHigh rateWeighted lifetimeNew symptomsHealth burdenLow prevalencePsychiatric disordersPTSD Checklist-5Late-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
Dimensional structure of DSM-5 posttraumatic stress disorder symptoms: results from the National Health and Resilience in Veterans Study.
Tsai J, Harpaz-Rotem I, Armour C, Southwick SM, Krystal JH, Pietrzak RH. Dimensional structure of DSM-5 posttraumatic stress disorder symptoms: results from the National Health and Resilience in Veterans Study. The Journal Of Clinical Psychiatry 2014, 76: 546-53. PMID: 25562376, DOI: 10.4088/jcp.14m09091.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderLifetime posttraumatic stress disorderHealth-related functioningMental health-related functioningDSM-5 posttraumatic stress disorderUS veteransSymptom clustersPTSD symptom clustersNational HealthVeterans StudyPTSD symptomsQuality of lifeDysphoric Arousal modelPosttraumatic stress disorder (PTSD) symptomsDSM-5 posttraumatic stress disorder symptomsDSM-5 PTSD symptom clustersHealth outcomesFemale veteransSuicidal ideationDSM-5 PTSD symptomsStress disorderSymptomsDisorder symptomsPTSD symptomatologyVeterans
2013
Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus
Pietrzak RH, Gallezot JD, Ding YS, Henry S, Potenza MN, Southwick SM, Krystal JH, Carson RE, Neumeister A. Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus. JAMA Psychiatry 2013, 70: 1199-1205. PMID: 24048210, PMCID: PMC4026855, DOI: 10.1001/jamapsychiatry.2013.399.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderNorepinephrine transporter availabilityLocus coeruleusPTSD groupTransporter availabilityHC groupVeterans Affairs Medical CenterStress disorderPTSD symptomsClinician-Administered PTSD ScalePositron emission tomography studyEmission tomography studiesPositron emission tomographyAnxious arousal symptomsNoradrenergic dysfunctionMedical CenterStudy groupMAIN OUTCOMEPTSD symptom clustersPTSD ScaleHealthy adultsCoeruleusBrain regionsChronic stressEmission tomography
1997
Noradrenergic and Serotonergic Function in Posttraumatic Stress Disorder
Southwick SM, Krystal JH, Bremner JD, Morgan CA, Nicolaou AL, Nagy LM, Johnson DR, Heninger GR, Charney DS. Noradrenergic and Serotonergic Function in Posttraumatic Stress Disorder. JAMA Psychiatry 1997, 54: 749-758. PMID: 9283511, DOI: 10.1001/archpsyc.1997.01830200083012.Peer-Reviewed Original ResearchConceptsYohimbine-induced panic attacksPosttraumatic stress disorderPanic attacksCardiovascular effectsCardiovascular measurementsStress disorderYohimbine hydrochloridePTSD symptomsDiastolic blood pressureDouble-blind fashionSeparate test daysGreater increaseBlood pressureIntravenous infusionSerotonergic functionNoradrenergic activitySerotonergic systemNoradrenergic systemHealthy subjectsSerotonergic activityPatientsDifferent patientsTest dayCombat veteransYohimbine
1995
Effects of the benzodiazepine antagonist flumazenil in PTSD
Randall P, Bremner J, Krystal J, Nagy L, Heninger G, Nicolaou A, Charney D. Effects of the benzodiazepine antagonist flumazenil in PTSD. Biological Psychiatry 1995, 38: 319-324. PMID: 7495926, DOI: 10.1016/0006-3223(94)00306-n.Peer-Reviewed Original ResearchConceptsVisual analogue rating scaleAdministration of flumazenilAnxiety symptomsCrossover study designBenzodiazepine antagonist flumazenilGABAA receptor complexBenzodiazepine/GABAA receptor complexPanic disorder patientsAnalogue rating scalesFlumazenil administrationPTSD Symptom ScaleIntravenous infusionAntagonist flumazenilGABAA antagonistHealthy controlsClinical studiesDisorder patientsSymptom ScaleFlumazenilPanic disorderPanic attacksVietnam combat veteransStudy designRating ScalePTSD symptoms
1994
Alcohol Dependence May Be the Missing Link Between Posttraumatic Stress Disorder and Panic-Reply
Krystal J, Southwick S, Charney D. Alcohol Dependence May Be the Missing Link Between Posttraumatic Stress Disorder and Panic-Reply. JAMA Psychiatry 1994, 51: 430-430. DOI: 10.1001/archpsyc.1994.03950050090014.Peer-Reviewed Original ResearchPanic disorderPTSD symptomsΑ2-adrenergic antagonistMajor psychiatric disordersPosttraumatic stress disorderAcute alcoholOpiate withdrawalMajor depressionNoradrenergic systemHealthy subjectsPsychiatric disordersClinical reportsAlcohol consumptionPatientsPanic attacksAlcohol dependenceSubstance abuseStress disorderNeurobiological significanceAnxiety disordersDisordersSymptomsPTSDWithdrawalLittle evidence