2015
Personalised pharmacotherapy: an interim solution for antidepressant treatment?
Chekroud AM, Krystal JH. Personalised pharmacotherapy: an interim solution for antidepressant treatment? The BMJ 2015, 350: h2502. PMID: 25976040, DOI: 10.1136/bmj.h2502.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
2007
The resistance to depressive relapse in menopausal women undergoing tryptophan depletion: preliminary findings
Epperson CN, Amin Z, Naftolin F, Cappiello A, Czarkowski KA, Stiklus S, Anderson GM, Krystal JH. The resistance to depressive relapse in menopausal women undergoing tryptophan depletion: preliminary findings. Journal Of Psychopharmacology 2007, 21: 414-420. PMID: 16891341, DOI: 10.1177/0269881106067330.Peer-Reviewed Original ResearchConceptsMenopausal womenTryptophan depletionSelective serotonin reuptake inhibitor fluoxetineAcute tryptophan depletion paradigmSerotonin reuptake inhibitor fluoxetineTryptophan depletion paradigmPathogenesis of depressionReuptake inhibitor fluoxetineMajor depressive episodeAcute tryptophan depletionRelapse of depressionWorsening of moodWeeks of recoveryActive tryptophan depletionWechsler Memory ScaleAssessment of moodDepressive episodeRisk factorsDepressive relapseMajor depressionSignificant worseningNeuroendocrine functionVerbal memorySerotonergic contributionMemory Scale
2005
Untangling depression and anxiety: clinical challenges.
Keller MB, Krystal JH, Hen R, Neumeister A, Simon NM. Untangling depression and anxiety: clinical challenges. The Journal Of Clinical Psychiatry 2005, 66: 1477-84. PMID: 16420087, DOI: 10.4088/jcp.v66n1119.Peer-Reviewed Original Researchγ-Aminobutyric Acid–Serotonin Interactions in Healthy Men: Implications for Network Models of Psychosis and Dissociation
D’Souza D, Gil RB, Zuzarte E, MacDougall LM, Donahue L, Ebersole JS, Boutros NN, Cooper T, Seibyl J, Krystal JH. γ-Aminobutyric Acid–Serotonin Interactions in Healthy Men: Implications for Network Models of Psychosis and Dissociation. Biological Psychiatry 2005, 59: 128-137. PMID: 16140281, DOI: 10.1016/j.biopsych.2005.06.020.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnxietyCross-Over StudiesDissociative DisordersDouble-Blind MethodDrug SynergismFlumazenilGABA ModulatorsGamma-Aminobutyric AcidHumansMaleModels, NeurologicalPerceptual DisordersPiperazinesPsychoses, Substance-InducedReceptors, GABA-AReceptors, Serotonin, 5-HT2Reference ValuesSerotoninSerotonin Receptor Agonists
2003
Neurobiological Correlates of the Disposition and Maintenance of Alcoholism
Heinz A, Schäfer M, Higley J, Krystal J, Goldman D. Neurobiological Correlates of the Disposition and Maintenance of Alcoholism. Pharmacopsychiatry 2003, 36: 255-258. PMID: 14677088, DOI: 10.1055/s-2003-45139.Peer-Reviewed Original ResearchConceptsAlcohol effectsMaintenance of alcoholismCurrent disease conceptsNeurobiological foundationsDispositional factorsNeurobiological correlatesMotivational therapyConsequences of alcoholismAlcohol cravingReward systemAlcohol intakeClinical withdrawalReduced controlTreatment of alcoholismChronic alcohol effectsNew treatment optionsNeuroadaptationsResearch pointsRelapse riskMonoaminergic dysfunctionPatient groupTreatment optionsGlutamatergic neurotransmissionCentral GABAergicPharmacological approaches
2001
Effect of Tryptophan Depletion on Alcohol Cue‐Induced Craving in Abstinent Alcoholic Patients
Petrakis I, Trevisan L, Boutros N, Limoncelli D, Cooney N, Krystal J. Effect of Tryptophan Depletion on Alcohol Cue‐Induced Craving in Abstinent Alcoholic Patients. Alcohol Clinical And Experimental Research 2001, 25: 1151-1155. PMID: 11505046, DOI: 10.1111/j.1530-0277.2001.tb02329.x.Peer-Reviewed Original ResearchConceptsCue-induced cravingAlcohol-dependent patientsTryptophan depletionAlcohol cue-induced cravingDouble-blind fashionPlasma free tryptophanAbstinent alcoholic patientsAmino acid drinkActive tryptophan depletionAlcoholic patientsSerotonin synthesisAcid drinkSober alcoholicsAlcoholic individualsPrecursor tryptophanCue exposurePatientsAlcohol useAbstinent alcoholic individualsCravingFree tryptophanAlcohol cuesTest dayGreater increaseSimilar drinks
2000
Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT
Laruelle M, Abi-Dargham A, van Dyck C, Gil R, D’Souza D, Krystal J, Seibyl J, Baldwin R, Innis R. Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT. Biological Psychiatry 2000, 47: 371-379. PMID: 10704949, DOI: 10.1016/s0006-3223(99)00257-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsBrain StemCarrier ProteinsCase-Control StudiesCocaineDopamineDopamine Plasma Membrane Transport ProteinsFemaleHumansIodine RadioisotopesMaleMembrane GlycoproteinsMembrane Transport ProteinsMiddle AgedNeostriatumNerve Tissue ProteinsSchizophreniaSerotoninSerotonin Plasma Membrane Transport ProteinsTomography, Emission-Computed, Single-PhotonConceptsAmphetamine-induced dopamine releaseStriatal dopamine transporterDopamine transporterControl subjectsDAT densityDopamine releaseNegative symptomsStriatal DAT densityDuration of illnessDopamine nerve terminalsHealthy control subjectsSerotonin transporter densityCohort of subjectsRelative deficitSingle photon emissionNeurodegenerative processesPostmortem studiesNerve terminalsSerotonin functionTrend-level associationReceptor radiotracerPatientsDopamine functionLower striatalTransporter density
1999
Neurotransmitter alterations in PTSD: catecholamines and serotonin.
Southwick SM, Paige S, Morgan CA, Bremner JD, Krystal JH, Charney DS. Neurotransmitter alterations in PTSD: catecholamines and serotonin. Seminars In Clinical Neuropsychiatry 1999, 4: 242-8. PMID: 10553029, DOI: 10.153/scnp00400242.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCatecholaminesHumansNeurotransmitter AgentsSerotoninStress Disorders, Post-TraumaticConceptsPost-traumatic stress disorderIntrusive memoriesLevel of alertnessSelective attentionAuditory remindersLife-threatening stimuliStress disorderCatecholamine dysregulationUrine catecholamine excretionExaggerated reactivityDepressed moodExaggerated startlePlatelet paroxetine bindingSerotonergic dysregulationAggressionClinical efficacyImpulsivityMotor outputBlunted prolactin responseMemoryMoodSerotonin reuptake inhibitorsAdrenergic receptor numberCentral catecholamine neuronsCentral nervous systemTryptophan-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
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 veteransYohimbinePositron Emission Tomography Measurement of Cerebral Metabolic Correlates of Tryptophan Depletion—Induced Depressive Relapse
Bremner JD, Innis RB, Salomon RM, Staib LH, Ng CK, Miller HL, Bronen RA, Krystal JH, Duncan J, Rich D, Price LH, Malison R, Dey H, Soufer R, Charney DS. Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Tryptophan Depletion—Induced Depressive Relapse. JAMA Psychiatry 1997, 54: 364-374. PMID: 9107153, DOI: 10.1001/archpsyc.1997.01830160092012.Peer-Reviewed Original ResearchConceptsCerebral metabolic correlatesDepressive relapseBrain metabolismMajor depressionMiddle frontal gyrusOrbitofrontal cortexTryptophan depletionMetabolic correlatesPositron emission tomography scanningFrontal gyrusRelapse-prone patientsPathogenesis of depressionPositron emission tomography (PET) measurementsSerotonin reuptake inhibitorsSymptoms of patientsPositron emission tomographySingle photon emissionSpecific brain regionsDorsolateral prefrontal cortexReuptake inhibitorsPlasma tryptophanLimbic regionsCaudate nucleusDepressive symptomsPatientsThe role of serotonin in the pathophysiology and treatment of schizophrenia
Abi-Dargham A, Laruelle M, Aghajanian GK, Charney D, Krystal J. The role of serotonin in the pathophysiology and treatment of schizophrenia. Journal Of Neuropsychiatry 1997, 9: 1-17. PMID: 9017523, DOI: 10.1176/jnp.9.1.1.Peer-Reviewed Original ResearchConceptsRole of serotoninBeneficial effectsSubcortical dopamine activityCerebrospinal fluid studiesCortex of patientsTreatment of schizophreniaBrain tissue analysisSerotonergic hypofunctionDopaminergic antagonistsPharmacological challengeDopamine activityNegative symptomsFluid studiesSchizophreniaPathophysiologySerotoninIllnessTissue analysisTreatmentMore researchAntagonismCompelling evidenceHypofunctionPatientsAntagonist
1996
Serotonergic 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 evidenceEffects of Rapid Tryptophan Depletion in Patients With Seasonal Affective Disorder in Remission After Light Therapy
Lam RW, Zis AP, Grewal A, Delgado PL, Charney DS, Krystal JH. Effects of Rapid Tryptophan Depletion in Patients With Seasonal Affective Disorder in Remission After Light Therapy. JAMA Psychiatry 1996, 53: 41-44. PMID: 8540776, DOI: 10.1001/archpsyc.1996.01830010043007.Peer-Reviewed Original ResearchConceptsRapid tryptophan depletionSeasonal affective disorderTryptophan depletionLight therapyClinical remissionAffective disordersTryptophan levelsDouble-blind crossover studyRecurrent major depressive episodesMajor depressive episodeBright light therapyEffect of therapyFree tryptophan levelsAntidepressant effectsCrossover studySerotonergic mechanismsDepressive episodeAntidepressant drugsTherapeutic effectSignificant relapseDepression scoresPatientsTherapyRemissionNonseasonal depression
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 changesTryptophan depletion and attenuation of cue-induced craving for cocaine
Satel SL, Krystal JH, Delgado PL, Kosten TR, Charney DS. Tryptophan depletion and attenuation of cue-induced craving for cocaine. American Journal Of Psychiatry 1995, 152: 778-783. PMID: 7726319, DOI: 10.1176/ajp.152.5.778.Peer-Reviewed Original ResearchConceptsCue-induced cravingTryptophan depletionPlacebo conditionPotent serotonin reuptake blockerCue exposureSerotonin reuptake blockersDouble-blind designAmino acid drinkVisual analogue ratingsCocaine-dependent patientsAnalogue ratingsReuptake blockerAcute reductionPlasma levelsSerotonergic systemMale inpatientsAcid drinkTryptophan levelsDrug usePatientsCocaine useCocaineRelapseCravingTest sessions
1994
Effects of sleep deprivation on serotonin function in depression
Salomon R, Delgado P, Licinio J, Krystal J, Heninger G, Charney D. Effects of sleep deprivation on serotonin function in depression. Biological Psychiatry 1994, 36: 840-846. PMID: 7893848, DOI: 10.1016/0006-3223(94)90595-9.Peer-Reviewed Original ResearchConceptsUndisturbed sleepSleep deprivationPRL riseDepressed patientsSerotonin functionFemale depressed patientsSD-induced changesIntravenous tryptophanAntidepressant treatmentPRL responseDepressed menTRP infusionScore changeMood changesPatientsMood ratingsMenProlactinConsiderable evidenceWomenLow sensitivitySignificant relationshipDeprivationInfusionSleep
1993
m-Chlorophenylpiperazine Effects in Neuroleptic-Free Schizophrenic Patients: Evidence Implicating Serotonergic Systems in the Positive Symptoms of Schizophrenia
Krystal JH, Seibyl JP, Price LH, Woods SW, Heninger GR, Aghajanian GK, Charney DS. m-Chlorophenylpiperazine Effects in Neuroleptic-Free Schizophrenic Patients: Evidence Implicating Serotonergic Systems in the Positive Symptoms of Schizophrenia. JAMA Psychiatry 1993, 50: 624-635. PMID: 8102048, DOI: 10.1001/archpsyc.1993.01820200034004.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleHealthy subjectsPsychiatric Rating ScalePositive symptomsSchizophrenic patientsPatient groupDouble-blind randomized comparisonVeterans Affairs Medical CenterRating ScaleNeuroleptic-free schizophrenic patientsFirst patient groupSerotonin partial agonistPrincipal outcome variableVisual analog scaleBaseline prolactin levelsHigher baseline levelsSymptoms of schizophreniaAnalog scaleRandomized comparisonAnxiogenic responseSum of scoresProlactin levelsSerotonergic systemSerotonin functionHormone levels