2020
Dopamine and glutamate in schizophrenia: biology, symptoms and treatment
McCutcheon RA, Krystal JH, Howes OD. Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry 2020, 19: 15-33. PMID: 31922684, PMCID: PMC6953551, DOI: 10.1002/wps.20693.Peer-Reviewed Original ResearchDopamine systemAberrant dopamine signallingStriatal dopamine synthesisNovel pharmacological therapiesPathophysiology of schizophreniaEnvironmental risk factorsPharmacological therapyGlutamatergic dysfunctionDopaminergic functionRisk factorsGlutamate systemDopamine synthesisGenetic risk variantsPreclinical studiesPsychotic symptomsDopamine functionNew treatmentsNeural circuitsDopamine signalingNeuronal signalingSchizophreniaConsistent findingRisk variantsSymptomsGlutamate
2013
Glutamatergic targets for new alcohol medications
Holmes A, Spanagel R, Krystal JH. Glutamatergic targets for new alcohol medications. Psychopharmacology 2013, 229: 539-554. PMID: 23995381, PMCID: PMC3811052, DOI: 10.1007/s00213-013-3226-2.Peer-Reviewed Original ResearchConceptsGlutamate systemGlycineB siteAlcohol-related behaviorsNMDA receptorsAlcohol abuseAlcohol consumptionN-methyl-D-aspartate receptorsChronic alcohol exposureElevated extracellular glutamatePathophysiology of alcoholismAMPA receptor subunitsAlcohol use disorderNovel pharmacotherapeutic approachesEffects of alcoholAlcohol medicationsBlocking NMDAHyperglutamatergic stateMetabotropic receptorsPharmacotherapeutic approachesAlcohol exposureExcess glutamateExtracellular glutamateGlutamate receptorsPreclinical studiesKainate receptors
2008
Corpus callosum in maltreated children with posttraumatic stress disorder: A diffusion tensor imaging study
Jackowski AP, Douglas-Palumberi H, Jackowski M, Win L, Schultz RT, Staib LW, Krystal JH, Kaufman J. Corpus callosum in maltreated children with posttraumatic stress disorder: A diffusion tensor imaging study. Psychiatry Research 2008, 162: 256-261. PMID: 18296031, PMCID: PMC3771642, DOI: 10.1016/j.pscychresns.2007.08.006.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderCorpus callosumStress disorderPathophysiology of PTSDDiffusion tensor imaging studyHistory of traumaWhite matter developmentEffects of stressWhite matter tractsWhite matter integrityDiffusion tensor imagingStudies of adultsInterhemispheric projectionsPediatric studiesPrimary white matter tractPreclinical studiesNormal controlsPosterior corpusHippocampus atrophyImaging studiesBrain structuresTensor imagingFractional anisotropyCallosumChildren
2007
The NMDA receptor as a therapeutic target in major depressive disorder.
Pittenger C, Sanacora G, Krystal JH. The NMDA receptor as a therapeutic target in major depressive disorder. CNS & Neurological Disorders - Drug Targets 2007, 6: 101-15. PMID: 17430148, DOI: 10.2174/187152707780363267.Peer-Reviewed Original ResearchConceptsMajor depressive disorderNMDA receptorsDepressive disorderNovel antidepressant medicationsCognitive side effectsPotential of drugsAntidepressant medicationAntidepressant propertiesSuch medicationsGlutamatergic neurotransmissionGlutamate receptorsPreclinical studiesPsychotomimetic propertiesSide effectsTherapeutic targetAnimal modelsUseful agentNeurotransmissionReceptorsLines of evidenceMedicationsDisordersDrugsCurrent knowledgeDepression
2000
Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine: Support for Hyperglutamatergic Effects of N-methyl-D-aspartate Receptor Antagonists
Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A, Krystal JH. Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine: Support for Hyperglutamatergic Effects of N-methyl-D-aspartate Receptor Antagonists. JAMA Psychiatry 2000, 57: 270-276. PMID: 10711913, DOI: 10.1001/archpsyc.57.3.270.Peer-Reviewed Original ResearchMeSH KeywordsAdultAffectBrief Psychiatric Rating ScaleCognition DisordersDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleGlutamatesHumansKetamineLamotrigineMaleMental DisordersPerceptual DisordersPlacebosPsychiatric Status Rating ScalesReceptors, N-Methyl-D-AspartateSchizophreniaSchizophrenic PsychologyTriazinesVerbal LearningConceptsN-methyl-D-aspartate receptor antagonistNMDA receptor dysfunctionReceptor antagonistNeuropsychiatric effectsGlutamate releaseReceptor dysfunctionSymptom subscalesPlacebo 2 hoursClinician-Administered Dissociative States ScaleAdministration of lamotrigineAdministration of ketamineDouble-blind conditionsNMDA receptor antagonistMood-elevating effectsPositive symptom subscaleBrief Psychiatric RatingNovel therapeutic agentsNegative symptom subscaleHopkins Verbal Learning TestVerbal Learning TestKetamine effectsPsychiatric illnessHealthy subjectsPathophysiologic processesPreclinical studies
1997
Evidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-Chlorophenylpiperazine (mCPP)
Krystal J, Webb E, Grillon C, Cooney N, Casal L, Morgan III. C, Southwick S, Davis M, Charney D. Evidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-Chlorophenylpiperazine (mCPP). Psychopharmacology 1997, 131: 207-215. PMID: 9203230, DOI: 10.1007/s002130050285.Peer-Reviewed Original ResearchConceptsHealthy subjectsAcoustic startle responseEthanol withdrawalStartle responseStartle magnitudeStartle amplitudeRandomized orderAcoustic startle magnitudeChronic alcoholic patientsSerotonin partial agonistDouble-blind conditionsAcoustic startle amplitudeNumber of episodesMale healthy subjectsΑ2-adrenergic antagonistTest dayMale patientsPlacebo dayAlcoholic patientsIntravenous infusionNoradrenergic functionYohimbine effectAlcohol detoxificationDrug infusionPreclinical studiesPositron 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
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
1990
Clinical data on the role of serotonin in the mechanism(s) of action of antidepressant drugs.
Price LH, Charney DS, Delgado PL, Goodman WK, Krystal JH, Woods SW, Heninger GR. Clinical data on the role of serotonin in the mechanism(s) of action of antidepressant drugs. The Journal Of Clinical Psychiatry 1990, 51 Suppl: 44-50; discussion 51-2. PMID: 2182616.Peer-Reviewed Original ResearchConceptsIntravenous L-tryptophanBrain serotonin functionAntidepressant drug actionRole of serotoninL-tryptophanThymoleptic drugsPlasma TrpView of evidencePRL responseNeuroendocrine effectsSerum prolactinSerotonin functionAntidepressant drugsClinical dataTherapeutic effectPreclinical studiesReceptor sensitivityClinical settingChallenge paradigmDrug actionRecent evidenceAntidepressantsProlactinDrugsDepressionClinical studies of 5-HT function using I.V. l-Tryptophan
Price L, Charney D, Delgado P, Goodman W, Krystal J, Woods S, Heninger G. Clinical studies of 5-HT function using I.V. l-Tryptophan. Progress In Neuro-Psychopharmacology And Biological Psychiatry 1990, 14: 459-472. PMID: 2236580, DOI: 10.1016/0278-5846(90)90002-x.Peer-Reviewed Original ResearchConceptsPRL responseClinical studiesDrug actionAntidepressant drug actionLong-term treatmentSuch clinical studiesThymoleptic drugsTime-dependent fashionPlasma TrpObsessive-compulsive disorderSerum prolactinElectrophysiological findingsDepressed patientsHealthy controlsAntidepressant drugsTherapeutic effectPreclinical studiesReceptor sensitivityPanic disorderChallenge agentNeuropsychiatric diseasesNeuropsychopharmacological studiesClinical levelCompulsive disorderL-Trp
1989
Neurobiological aspects of PTSD: Review of clinical and preclinical studies
Krystal J, Kosten T, Southwick S, Mason J, Perry B, Giller E. Neurobiological aspects of PTSD: Review of clinical and preclinical studies. Behavior Therapy 1989, 20: 177-198. DOI: 10.1016/s0005-7894(89)80068-1.Peer-Reviewed Original Research