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 ResearchMicroglia-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 symptomsAnhedoniaDexmedetomidine 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 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 analysisDeficitsProblem Opioid Use Among US Military Veterans: Prevalence, Correlates, and Psychiatric Characteristics
Na P, Petrakis I, Krystal J, Pietrzak R. Problem Opioid Use Among US Military Veterans: Prevalence, Correlates, and Psychiatric Characteristics. Journal Of Addiction Medicine 2024, 18: 313-318. PMID: 38498625, PMCID: PMC11150085, DOI: 10.1097/adm.0000000000001286.Peer-Reviewed Original ResearchInstrumental activities of daily livingInstrumental activities of daily living disabilityLifetime suicide attemptsProblem opioid useUS military veteransUS veteransPsychiatric characteristicsSuicide attemptsMilitary veteransAssociated with black race/ethnicityActivities of daily livingNational Health and ResilienceLifetime alcohol use disorderMental health morbidityPosttraumatic stress disorderMental health disordersAlcohol use disorderNon-Hispanic race/ethnicityMultivariate logistic regression modelNationally representative sampleOpioid useLogistic regression modelsInstrumental activitiesHealth morbidityDaily living
2023
Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods
Yang J, Huggins A, Sun D, Baird C, Haswell C, Frijling J, Olff M, van Zuiden M, Koch S, Nawijn L, Veltman D, Suarez-Jimenez B, Zhu X, Neria Y, Hudson A, Mueller S, Baker J, Lebois L, Kaufman M, Qi R, Lu G, Říha P, Rektor I, Dennis E, Ching C, Thomopoulos S, Salminen L, Jahanshad N, Thompson P, Stein D, Koopowitz S, Ipser J, Seedat S, du Plessis S, van den Heuvel L, Wang L, Zhu Y, Li G, Sierk A, Manthey A, Walter H, Daniels J, Schmahl C, Herzog J, Liberzon I, King A, Angstadt M, Davenport N, Sponheim S, Disner S, Straube T, Hofmann D, Grupe D, Nitschke J, Davidson R, Larson C, deRoon-Cassini T, Blackford J, Olatunji B, Gordon E, May G, Nelson S, Abdallah C, Levy I, Harpaz-Rotem I, Krystal J, Morey R, Sotiras A. Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods. Neuropsychopharmacology 2023, 49: 609-619. PMID: 38017161, PMCID: PMC10789873, DOI: 10.1038/s41386-023-01763-5.Peer-Reviewed Original ResearchPosttraumatic stress disorderStructural covariance networksCortical thicknessPTSD diagnosisInsular cortexPTSD patientsCingulate cortexSymptom severityBilateral superior frontal cortexStress disorderGreater cortical thicknessLower cortical thicknessChildhood trauma severitySuperior frontal cortexRegression analysisAnterior cingulate cortexTrauma-exposed controlsPosterior cingulate cortexPrefrontal regulatory regionsPTSD symptom severityComorbid depressionMotor cortexHealthy controlsFrontal cortexAlcohol abuseDSM-5 Criterion-A-Based Trauma Types in Service Members and Veterans Seeking Treatment for Posttraumatic Stress Disorder
Benfer N, Grunthal B, Dondanville K, Young-McCaughan S, Blankenship A, Abdallah C, Back S, Flanagan J, Foa E, Fox P, Krystal J, Marx B, McGeary D, McLean C, Pruiksma K, Resick P, Roache J, Shiroma P, Sloan D, Taylor D, Wachen J, López-Roca A, Nicholson K, Schobitz R, Schrader C, Sharrieff A, Yarvis J, Mintz J, Keane T, Peterson A, Litz B. DSM-5 Criterion-A-Based Trauma Types in Service Members and Veterans Seeking Treatment for Posttraumatic Stress Disorder. Psychological Trauma Theory Research Practice And Policy 2023, 16: 1218-1228. PMID: 37410416, PMCID: PMC10770283, DOI: 10.1037/tra0001537.Peer-Reviewed Original ResearchPosttraumatic stress disorderTrauma typesBehavioral health problemsHealth problemsStress disorderMoral injuryParticipants' ratingsLife threatAftermath of violenceMental health problemsDSM-5 criteriaTraumatic eventsParticipants' endorsementClinical trialsDifferent traumasTyping schemeTraumatic lossAssessor judgementsService membersTraumaClinical researchersParticipantsUnique contextInjuryMilitary personnelA computational model for learning from repeated traumatic experiences under uncertainty
Kaye A, Rao M, Kwan A, Ressler K, Krystal J. A computational model for learning from repeated traumatic experiences under uncertainty. Cognitive, Affective, & Behavioral Neuroscience 2023, 23: 894-904. PMID: 37165181, PMCID: PMC11149767, DOI: 10.3758/s13415-023-01085-5.Peer-Reviewed Original ResearchPosttraumatic stress disorderTraumatic eventsNovel contextThreat perceptionTreatment of PTSDEarly life traumaNeutral cuesThreat responsesStress disorderLife traumaTraumatic experiencesPrediction errorComputational theorySensory cuesPTSD incidenceNovel predictionsUnpredictable footshockInternal statesComputational modelCuesPerceptionSpecific associationFootshockContextTheoryNeural 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 gainsTrajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study
Na P, Montalvo-Ortiz J, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Trajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study. Drug And Alcohol Dependence 2023, 246: 109833. PMID: 36963160, PMCID: PMC10811960, DOI: 10.1016/j.drugalcdep.2023.109833.Peer-Reviewed Original ResearchConceptsAlcohol consumption groupCurrent mental health treatmentDysphoric arousal symptomsMental health treatmentUS veteransAlcohol consumptionHealth treatmentConsumption groupArousal symptomsYounger agePopulation-based longitudinal studyPublic health problemLongitudinal studyExcessive alcohol consumptionAlcohol use disorderPosttraumatic stress disorderU.S. military veteransMedical comorbiditiesChronic courseNational HealthClose monitoringUse disordersHealth problemsVeterans StudyStress disorderCross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review
Núñez-Rios D, Martínez-Magaña J, Nagamatsu S, Krystal J, Martínez-González K, Giusti-Rodríguez P, Montalvo-Ortiz J. Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review. Complex Psychiatry 2023, 9: 100-118. PMID: 37404872, PMCID: PMC10315001, DOI: 10.1159/000529536.Peer-Reviewed Original ResearchG protein-coupled receptorsPosttraumatic stress disorderEpigenomic findingsEpigenomic studiesEpigenomic profilesTranscriptomic modificationsEpigenetic studiesBrain transcriptomicsBiological pathwaysComplex multifactorial disorderGenesBrain tissueGene-environment interplayStress disorderSpeciesHuman postmortem samplesChemical synaptic transmissionSystematic literature searchEnvironmental factorsCurrent knowledge gapsPotential roleOrexin pathwayPathwayBrain alterationsPeripheral tissuesPsychometric 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
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
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 ResearchRemodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder: Results From the ENIGMA-PGC Posttraumatic Stress Disorder Consortium
Sun D, Rakesh G, Clarke-Rubright EK, Haswell CC, Logue MW, O'Leary EN, Cotton AS, Xie H, Dennis EL, Jahanshad N, Salminen LE, Thomopoulos SI, Rashid FM, Ching CRK, Koch SBJ, Frijling JL, Nawijn L, van Zuiden M, Zhu X, Suarez-Jimenez B, Sierk A, Walter H, Manthey A, Stevens JS, Fani N, van Rooij SJH, Stein MB, Bomyea J, Koerte I, Choi K, van der Werff SJA, Vermeiren RRJM, Herzog JI, Lebois LAM, Baker JT, Ressler KJ, Olson EA, Straube T, Korgaonkar MS, Andrew E, Zhu Y, Li G, Ipser J, Hudson AR, Peverill M, Sambrook K, Gordon E, Baugh LA, Forster G, Simons RM, Simons JS, Magnotta VA, Maron-Katz A, du Plessis S, Disner SG, Davenport ND, Grupe D, Nitschke JB, deRoon-Cassini TA, Fitzgerald J, Krystal JH, Levy I, Olff M, Veltman DJ, Wang L, Neria Y, De Bellis MD, Jovanovic T, Daniels JK, Shenton ME, van de Wee NJA, Schmahl C, Kaufman ML, Rosso IM, Sponheim SR, Hofmann DB, Bryant RA, Fercho KA, Stein DJ, Mueller SC, Phan KL, McLaughlin KA, Davidson RJ, Larson C, May G, Nelson SM, Abdallah CG, Gomaa H, Etkin A, Seedat S, Harpaz-Rotem I, Liberzon I, Wang X, Thompson PM, Morey RA. Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder: Results From the ENIGMA-PGC Posttraumatic Stress Disorder Consortium. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2022, 7: 935-948. PMID: 35307575, PMCID: PMC9835553, DOI: 10.1016/j.bpsc.2022.02.008.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderCortical thicknessStructural covarianceComorbid depressionControl subjectsLarge effect sizesStress disorderEffect sizeTrauma-exposed control subjectsCase-control differencesCortical surface areaInflammatory processClinical dataResting-state functional connectivity networksPositive pairwise correlationsCortical differencesCortical regionsCortical neuroanatomyStress hormonesFunctional connectivity networksPTSD casesSmall effect sizesGroup differencesStructural networkStructural connectomePosttraumatic Stress Disorder in US Military Veterans: Results From the 2019-2020 National Health and Resilience in Veterans Study.
Wisco BE, Nomamiukor FO, Marx BP, Krystal JH, Southwick SM, Pietrzak RH. Posttraumatic Stress Disorder in US Military Veterans: Results From the 2019-2020 National Health and Resilience in Veterans Study. The Journal Of Clinical Psychiatry 2022, 83 PMID: 35192748, DOI: 10.4088/jcp.20m14029.Peer-Reviewed Original ResearchConceptsUS military veteransPosttraumatic stress disorderLifetime posttraumatic stress disorderFunctional impairmentMilitary veteran populationNational HealthMilitary veteransVeteran populationVeterans StudyTrauma exposureStress disorderGreater functional impairmentPTSD Criterion ALife Events Checklist-5Odds of lifetimeWeighted prevalencePTSD prevalenceIndirect trauma exposurePTSD ChecklistPrevalenceImpairmentPsychiatric variablesVeteransContemporary dataCriterion APolygenic 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 severityDepressionEpigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans
Montalvo-Ortiz JL, Gelernter J, Cheng Z, Girgenti MJ, Xu K, Zhang X, Gopalan S, Zhou H, Duman RS, Southwick SM, Krystal JH, Pietrzak R. Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans. Translational Psychiatry 2022, 12: 65. PMID: 35177594, PMCID: PMC8854688, DOI: 10.1038/s41398-022-01822-3.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesAssociation studiesTranscription regulationCpG sitesGenome-wide association studiesCell type proportionsPosttraumatic stress disorderPotential epigenetic biomarkersSignificant CpG sitesEpigenetic mechanismsDNA methylationNovel lociCell signalingEpigenetic biomarkersMethylation analysisAxonal guidanceNovel molecular biomarkersEPIC BeadChipLifetime posttraumatic stress disorderMilitary veteransPostmortem brain tissueMedial orbitofrontal cortexMolecular biomarkersRegulationU.S. military veteransImaging 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 symptomsDose-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