2018
Locus Coeruleus Hyperactivity in Posttraumatic Stress Disorder: Answers and Questions
Krystal JH, Abdallah CG, Pietrzak RH, Averill LA, Harpaz-Rotem I, Levy I, Kelmendi B, Southwick SM. Locus Coeruleus Hyperactivity in Posttraumatic Stress Disorder: Answers and Questions. Biological Psychiatry 2018, 83: 197-199. PMID: 29277190, DOI: 10.1016/j.biopsych.2017.09.027.Peer-Reviewed Original Research
2016
Glutamate and norepinephrine interaction: Relevance to higher cognitive operations and psychopathology
Abdallah CG, Averill LA, Krystal JH, Southwick SM, Arnsten AF. Glutamate and norepinephrine interaction: Relevance to higher cognitive operations and psychopathology. Behavioral And Brain Sciences 2016, 39: e201. PMID: 28347382, PMCID: PMC5485236, DOI: 10.1017/s0140525x15001727.Peer-Reviewed Original Research
2009
Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience
Krystal JH, Neumeister A. Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience. Brain Research 2009, 1293: 13-23. PMID: 19332037, PMCID: PMC2761677, DOI: 10.1016/j.brainres.2009.03.044.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStress disorderOrdinary stressful life eventsEtiology of PTSDNeurobiology of PTSDSymptoms of PTSDImpact of traumaStressful life eventsTraumatic eventsNeurobiological systemsLife eventsTreatment developmentSerotonergic mechanismsNeurobiologyUse of antidepressantsDevelopment of treatmentsBasic researchResilienceMonoaminergic mechanismsAvailable treatmentsRelevant findingsHyperarousalResearchDisordersPsychopathology
2000
Cocaine use and the mid-latency auditory evoked responses
Boutros N, Campbell D, Petrakis I, Krystal J, Caporale M, Kosten T. Cocaine use and the mid-latency auditory evoked responses. Psychiatry Research 2000, 96: 117-126. PMID: 11063784, DOI: 10.1016/s0165-1781(00)00207-9.Peer-Reviewed Original ResearchConceptsCocaine-dependent subjectsInter-stimulus intervalMid-latency auditoryAge-matched healthy control subjectsCocaine useHealthy control subjectsDifferent inter-stimulus intervalsChronic cocaine useLong inter-stimulus intervalsPaired-click paradigmControl subjectsP50 componentN100 componentSignificant decreaseSubjectsAuditoryResponse paradigm
1999
Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action
Delgado P, Miller H, Salomon R, Licinio J, Krystal J, Moreno F, Heninger G, Charney D. Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action. Biological Psychiatry 1999, 46: 212-220. PMID: 10418696, DOI: 10.1016/s0006-3223(99)00014-1.Peer-Reviewed Original ResearchConceptsTRP depletionAntidepressant responseDepressed patientsSuccessful antidepressant treatmentBrain serotonin contentSignificant depressive symptomsAmino acid drinkRole of serotoninMonoamine oxidase inhibitorsRelationship of relapseAntidepressant actionAntidepressant treatmentReuptake inhibitorsPlasma tryptophanPlasma levelsAntidepressant typeTherapeutic responseDepressive relapseSerotonin contentTherapeutic effectTRP levelsDepressive symptomsTreatment phasePatientsAcid drink
1997
Effect of alpha-methyl-para-tyrosine on response to cocaine challenge
Stine S, Krystal J, Petrakis I, Jatlow P, Heninger G, Kosten T, Chamey D. Effect of alpha-methyl-para-tyrosine on response to cocaine challenge. Biological Psychiatry 1997, 42: 181-190. PMID: 9232210, DOI: 10.1016/s0006-3223(96)00331-9.Peer-Reviewed Original ResearchConceptsDopamine metabolite homovanillic acidCocaine-induced euphoriaNorepinephrine metabolite 3Placebo-controlled studyBlood pressure responseMetabolite homovanillic acidReduced plasma levelsTyrosine hydroxylase inhibitorSerum cocaine levelsTuberoinfundibular dopamine systemAMPT pretreatmentAcute reductionIntranasal administrationPara-tyrosinePlasma levelsProlactin levelsCocaine challengeHomovanillic acidCatecholamine synthesisHeart rateHydroxylase inhibitorAlpha-methylDopamine systemCocaine levelsTherapeutic potentialNoradrenergic 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 veteransYohimbineNoradrenergic Alterations in Posttraumatic Stress Disorder
SOUTHWICK S, MORGAN CA, BREMNER A, GRILLON C, KRYSTAL J, NAGY L, CHARNEY D. Noradrenergic Alterations in Posttraumatic Stress Disorder. Annals Of The New York Academy Of Sciences 1997, 821: 125-141. PMID: 9238199, DOI: 10.1111/j.1749-6632.1997.tb48274.x.Peer-Reviewed Original ResearchPositron Emission Tomography Measurement of Cerebral Metabolic Correlates of Yohimbine Administration in Combat-Related Posttraumatic Stress Disorder
Bremner JD, Innis RB, Ng CK, Staib LH, Salomon RM, Bronen RA, Duncan J, Southwick SM, Krystal JH, Rich D, Zubal G, Dey H, Soufer R, Charney DS. Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Yohimbine Administration in Combat-Related Posttraumatic Stress Disorder. JAMA Psychiatry 1997, 54: 246-254. PMID: 9075465, DOI: 10.1001/archpsyc.1997.01830150070011.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderAdministration of yohimbineNorepinephrine releaseHealthy subjectsHealthy age-matched control subjectsAge-matched control subjectsStress disorderDouble-blind fashionPositron emission tomography (PET) measurementsBrain metabolic responsesCerebral metabolic correlatesBrain norepinephrine releaseSymptoms of anxietyPositron emission tomographyBrain metabolismControl subjectsYohimbine administrationPreclinical studiesMetabolic correlatesCaudate nucleusPatientsYohimbineVietnam combat veteransEmission tomographyOrbitofrontal cortex
1996
Noradrenergic mechanisms in stress and anxiety: I. preclinical studies
Bremner J, Krystal J, Southwick S, Charney D. Noradrenergic mechanisms in stress and anxiety: I. preclinical studies. Synapse 1996, 23: 28-38. PMID: 8723133, DOI: 10.1002/(sici)1098-2396(199605)23:1<28::aid-syn4>3.0.co;2-j.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderBrain regionsNoradrenergic brain systemsMultiple subcortical areasConsiderable preclinical evidenceLocus coeruleusBrain systemsNeural mechanismsStress disorderTarget brain regionsBehavioral manifestationsBrain functionPanic disorderStress exposureChronic stress resultsTurnover of norepinephrineSubcortical areasAnxietyPsychiatric disordersNoradrenergic systemLong-term alterationsNoradrenergic mechanismsNoradrenergic neuronsNorepinephrine releasePreclinical evidenceNimodipine reduction of naltrexone-precipitated locus coeruleus activation and abstinence behavior in morphine-dependent rats
Krystal J, Compere S, Nestler E, Rasmussen K. Nimodipine reduction of naltrexone-precipitated locus coeruleus activation and abstinence behavior in morphine-dependent rats. Physiology & Behavior 1996, 59: 863-866. PMID: 8778878, DOI: 10.1016/0031-9384(95)02206-6.Peer-Reviewed Original ResearchConceptsL-type calcium channel antagonistLocus coeruleus neuronsMorphine-dependent ratsOpiate-dependent ratsCalcium channel antagonistsSingle-unit recordingsLocus coeruleus activationNimodipine effectCoeruleus neuronsNoradrenergic mechanismsOpiate withdrawalLocus coeruleusChannel antagonistsAnesthetized animalsNimodipineAbstinence behaviorTime courseRatsWithdrawal behaviorActivationNaltrexoneCoeruleusClinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression
Miller HL, Delgado PL, Salomon RM, Berman R, Krystal JH, Heninger GR, Charney DS. Clinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression. JAMA Psychiatry 1996, 53: 117-128. PMID: 8629887, DOI: 10.1001/archpsyc.1996.01830020031005.Peer-Reviewed Original ResearchConceptsNorepinephrine reuptake inhibitorsReuptake inhibitorsCatecholamine depletionAlpha-methylparatyrosineTreatment groupsHamilton Depression Rating ScaleHomovanillic acid levelsSerotonin reuptake inhibitorsDepression Rating ScaleSimilar significant decreaseAntihistamine diphenhydramine hydrochlorideSeparate test sessionsFeelings of worthlessnessConsiderable sedationLoss of interestDepressed patientsDepressive relapseAntidepressant drugsInactive placeboTherapeutic effectTherapeutic mechanismDepressive symptomsCatecholamine metabolitesPlasma 3RemissionSerotonergic and noradrenergic dysregulation in alcoholism: m- chlorophenylpiperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects
Krystal JH, Webb E, Cooney NL, Kranzler HR, Southwick SW, Heninger GR, Charney DS. Serotonergic and noradrenergic dysregulation in alcoholism: m- chlorophenylpiperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects. American Journal Of Psychiatry 1996, 153: 83-92. PMID: 8540598, DOI: 10.1176/ajp.153.1.83.Peer-Reviewed Original ResearchConceptsHealthy comparison subjectsAlcoholic patientsComparison subjectsCortisol responseYohimbine infusionPostsynaptic noradrenergic receptorsBlood pressure responseDouble-blind conditionsNoradrenergic reactivitySaline placeboNoradrenergic receptorsMHPG levelsIntravenous infusionYohimbine effectMHPG responsePlasma levelsNoradrenergic systemPersistent alterationsNoradrenergic dysregulationMale inpatientsDrug effectsNeuroendocrine responsivityPatientsPhysiologic responsesPlasma cortisolThe biological basis of panic disorder.
Krystal JH, Deutsch DN, Charney DS. The biological basis of panic disorder. The Journal Of Clinical Psychiatry 1996, 57 Suppl 10: 23-31; discussion 32-3. PMID: 8917129.Peer-Reviewed Original ResearchConceptsPanic disorderMultiple neuronal systemsRelated brain regionsFunctional imaging studiesOvert historyPharmacologic mechanismsTreatment optionsPharmacologic challengePanicogenic agentPreclinical investigationsNeurochemical substratesPanic attacksChallenge studiesBrain regionsImaging studiesAnatomical basisNeuronal systemsAnxiety disordersDisordersHeritable predispositionBiological basisFurther evidence
1995
Effects of tryptophan depletion on responses to yohimbine in healthy human subjects
Goddard A, Charney D, Germine M, Woods S, Heninger G, Krystal J, Goodman W, Price L. Effects of tryptophan depletion on responses to yohimbine in healthy human subjects. Biological Psychiatry 1995, 38: 74-85. PMID: 7578653, DOI: 10.1016/0006-3223(94)00223-p.Peer-Reviewed Original ResearchConceptsHealthy human subjectsTryptophan depletionAlpha-2 adrenergic antagonist yohimbinePlacebo-controlled challenge testHuman subjectsAntagonist yohimbineNeurotransmitter systemsSerotonin systemChallenge testPossible functional interactionBiochemical variablesWhole groupFeelings of nervousnessNE functionMarked increaseNorepinephrineConsiderable evidenceFear responsesSubjectsHuman anxietyNervousnessCombination testControl testsFunctional interactionUnique changesNoradrenergic response to acute ethanol administration in heathly subjects: comparison with intravenous yohimbine
McDougle C, Price L, Heninger G, Krystal J, Charney D. Noradrenergic response to acute ethanol administration in heathly subjects: comparison with intravenous yohimbine. Psychopharmacology 1995, 118: 127-135. PMID: 7617798, DOI: 10.1007/bf02245830.Peer-Reviewed Original ResearchConceptsAcute ethanol administrationEthanol administrationPlasma MHPGIntravenous yohimbineBlood pressureNE turnoverSystolic blood pressureAlpha2-adrenergic receptorsPlacebo-controlled designBlood pressure measurementsEthanol-induced increaseHealthy human subjectsClear additive effectSubjective measuresNE metabolismNoradrenergic responsesNorepinephrine metaboliteCombined administrationMHPG responsePlasma levelsPharmacokinetic effectsOral administrationIntravenous administrationAnxiogenic effectsEthanol intoxication
1994
Psychobiologic Research in Post-Traumatic Stress Disorder
Southwick S, Bremner D, Krystal J, Charney D. Psychobiologic Research in Post-Traumatic Stress Disorder. Psychiatric Clinics Of North America 1994, 17: 251-264. PMID: 7937357, DOI: 10.1016/s0193-953x(18)30112-6.Peer-Reviewed Original ResearchConceptsNeurobiologic responsesCentral nervous system depressantsCentral catecholamine functionPeripheral nervous systemPost-traumatic stress disorderSymptoms of hyperarousalSevere psychological traumaCatecholamine functionOriginal insultNoradrenergic systemMultiple symptomsDevastating disorderEffective treatmentNervous systemPTSD patientsBiologic underpinningsStress-induced changesStress disorderPhysical healthBrain imagingBiologic responseDisordersPatientsPsychological disordersPTSD
1993
Yohimbine — facilitated acoustic startle reflex in humans
Morgan CA, Southwick SM, Grillon C, Davis M, Krystal JH, Charney DS. Yohimbine — facilitated acoustic startle reflex in humans. Psychopharmacology 1993, 110: 342-346. PMID: 7831429, DOI: 10.1007/bf02251291.Peer-Reviewed Original ResearchConceptsAcoustic startle reflexHealthy subjectsRandomized double-blind placebo-controlled designStartle amplitudeDouble-blind placebo-controlled designStartle reflexAlpha-2 receptor antagonistEffects of yohimbinePlacebo-controlled designDB intensityUseful animal modelHealthy human subjectsInstantaneous rise timeSaline placeboCardiovascular effectsExcitatory effectsNoradrenergic functionReceptor antagonistPlasma MHPGPreclinical studiesPeak anxietyYohimbineNeurochemical basisAnimal modelsRank testing
1992
Noradrenergic neuronal dysregulation in panic disorder: the effects of intravenous yohimbine and clonidine in panic disorder patients
Charney DS, Woods SW, Krystal JH, Nagy LM, Heninger GR. Noradrenergic neuronal dysregulation in panic disorder: the effects of intravenous yohimbine and clonidine in panic disorder patients. Acta Psychiatrica Scandinavica 1992, 86: 273-282. PMID: 1333719, DOI: 10.1111/j.1600-0447.1992.tb03266.x.Peer-Reviewed Original ResearchConceptsPanic disorder patientsDisorder patientsPanic disorderIntravenous yohimbineHealthy subjectsYohimbine-induced panic attacksClonidine-induced decreaseYohimbine-induced increasesGrowth hormone responseNeuronal dysregulationCardiovascular effectsPlasma MHPGPatientsPlasma 3Hormone responseNeuronal functionPanic attacksClonidineHuman dataDisordersYohimbineHuman anxietySubgroupsFear statesFunctional regulation
1990
Noradrenergic function in panic disorder.
Charney DS, Woods SW, Nagy LM, Southwick SM, Krystal JH, Heninger GR. Noradrenergic function in panic disorder. The Journal Of Clinical Psychiatry 1990, 51 Suppl A: 5-11. PMID: 2258377.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnxiety DisordersCatsHumansLocus CoeruleusMacacaModels, NeurologicalNorepinephrinePanicSympathetic Nervous SystemConceptsLocus ceruleusNoradrenergic functionPanic disorderBrain noradrenergic functionNoradrenergic neuronal activityPanic disorder patientsNoradrenergic neuronsPreclinical evidenceNatural courseNoradrenergic nucleusDevelopment of anxietyAnxiogenic effectsClinical investigationDisorder patientsNeuronal activityUncontrollable stressNeuron firingNonhuman primatesNeurodevelopmental perspectiveLaboratory animalsSystem regulationFear responsesDisordersAnxietyElectrical activation