2023
Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge
Tamman A, Koller D, Nagamatsu S, Cabrera-Mendoza B, Abdallah C, Krystal J, Gelernter J, Montalvo-Ortiz J, Polimanti R, Pietrzak R. Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge. Neuropsychopharmacology 2023, 49: 699-708. PMID: 37848731, PMCID: PMC10876568, DOI: 10.1038/s41386-023-01747-5.Peer-Reviewed Original ResearchPolygenic risk scoresRisk scoreGenetic predispositionModifiable psychosocial variablesAge-related morbidityGamma-glutamyl transferaseInflammatory biomarkersSystemic inflammationNational HealthApolipoprotein BMale veteransPsychosocial factorsVeterans StudySaliva samplesPsychosocial moderatorsPsychosocial variablesAntihistamine drugsMilitary veteransGrimAgeGrimAge accelerationInflammationUK BiobankDrugsRepresentative samplePredisposition
2021
Potential Schizophrenia Medications Point to New Disease Model
Krystal J. Potential Schizophrenia Medications Point to New Disease Model. Psychiatric News 2021, 56 DOI: 10.1176/appi.pn.2021.11.37.Peer-Reviewed Original ResearchDopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia
Abi-Dargham A, Javitch JA, Slifstein M, Anticevic A, Calkins ME, Cho YT, Fonteneau C, Gil R, Girgis R, Gur RE, Gur RC, Grinband J, Kantrowitz J, Kohler C, Krystal J, Murray J, Ranganathan M, Santamauro N, Van Snellenberg J, Tamayo Z, Wolf D, D’Souza D, Srihari V, Gueorguieva R, Patel P, Forselius-Bielen K, Lu J, Butler A, Fram G, Afriyie-Agyemang Y, Selloni A, Cadavid L, Gomez-Luna S, Gupta A, Radhakrishnan R, Rashid A, Aker R, Abrahim P, Nia A, Surti T, Kegeles L, Carlson M, Goldberg T, Gangwisch J, Benedict E, Govil P, Brazis S, Mayer M, de la Garrigue N, Fallon N, Baumvoll T, Abeykoon S, Perlman G, Bobchin K, Elliott M, Schmidt L, Rush S, Port A, Heffernan Z, Laney N, Kantor J, Hohing T, Gray D, Lieberman J. Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. Schizophrenia Bulletin 2021, 48: 199-210. PMID: 34423843, PMCID: PMC8781338, DOI: 10.1093/schbul/sbab095.Peer-Reviewed Original ResearchConceptsCortical dopamine neurotransmissionPositive allosteric modulationImportant therapeutic targetPF-06412562Dopaminergic receptorsD1R stimulationDA levelsTolerable dosesLevel of stimulationDopamine neurotransmissionReceptor stimulationTherapeutic targetPartial agonistCognitive deficitsBiased agonismFull agonismTarget engagementAllosteric modulationNew drugsStimulationPoor bioavailabilitySchizophreniaOptimal stimulationDrugsExpression levels
2008
Modulation of the cortical processing of novel and target stimuli by drugs affecting glutamate and GABA neurotransmission
Watson TD, Petrakis IL, Edgecombe J, Perrino A, Krystal JH, Mathalon DH. Modulation of the cortical processing of novel and target stimuli by drugs affecting glutamate and GABA neurotransmission. The International Journal Of Neuropsychopharmacology 2008, 12: 357-370. PMID: 18771605, PMCID: PMC2900256, DOI: 10.1017/s1461145708009334.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceCerebral CortexDouble-Blind MethodElectroencephalographyEvoked PotentialsFemaleGABA ModulatorsHumansKetamineMalePain MeasurementPattern Recognition, VisualPhotic StimulationReaction TimeReceptors, GABA-BReceptors, N-Methyl-D-AspartateStatistics as TopicThiopentalYoung AdultConceptsPlacebo-controlled studyNMDA receptor systemSubanaesthetic dosesGABA neurotransmissionChallenge sessionsDrug effectsNMDA antagonismHealthy adultsNovel stimuliCortical processingReceptor systemPlaceboDrugsCounterbalanced orderKetaminePotential correlatesNeural correlatesP3a amplitudeNovelty processingP300 componentStandard stimuliStimulus processingStimuliTarget stimuliN2 amplitude
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
1999
Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation.
Chambers RA, Bremner JD, Moghaddam B, Southwick SM, Charney DS, Krystal JH. Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation. Seminars In Clinical Neuropsychiatry 1999, 4: 274-81. PMID: 10553033, DOI: 10.153/scnp00400274.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderGlutamate releaseNMDA antagonistsStress disorderN-methyl-D-aspartate (NMDA) subtypeDevelopment of PTSDDissociative symptomsStress exposureRecent preclinical dataTraumatic stress exposureHyperglutamatergic stateNeuroprotective potentialPreclinical dataNeural toxicityClinical studiesGlutamate receptorsTraumatized individualsPerceptual effectsPerceptual alterationsNeural plasticityAntagonistBrain functionSymptomsInfluence behaviorDrugs
1991
Mechanisms of action of atypical antipsychotic drugs Implications for novel therapeutic strategies for schizophrenia
Deutch A, Moghaddam B, Innis R, Krystal J, Aghajanian G, Bunney B, Charney D. Mechanisms of action of atypical antipsychotic drugs Implications for novel therapeutic strategies for schizophrenia. Schizophrenia Research 1991, 4: 121-156. PMID: 1674882, DOI: 10.1016/0920-9964(91)90030-u.Peer-Reviewed Original ResearchConceptsAtypical antipsychotic drugsAntipsychotic drugsDopamine D2 receptor antagonismD2 receptor antagonismAtypical profileNovel therapeutic strategiesDopamine D2 receptorsMechanism of actionAtypical agentsReceptor antagonismClinical dataD2 receptorsTherapeutic strategiesDrug profileDrugs implicationsMode of actionDrugsAntagonismClozapineRacloprideSerotoninSubtypesSchizophrenia
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 evidenceAntidepressantsProlactinDrugsDepressionSerotonin-Specific Drugs for Anxiety and Depressive Disorders
Charney DS, Krystal JH, Delgado PL, Heninger GR. Serotonin-Specific Drugs for Anxiety and Depressive Disorders. Annual Review Of Medicine 1990, 41: 437-446. PMID: 2139556, DOI: 10.1146/annurev.me.41.020190.002253.Peer-Reviewed Original Research
1989
Effects of alprazolam and clonidine on carbon dioxide-induced increases in anxiety ratings in healthy human subjects
Woods S, Krystal J, Heninger G, Charney D. Effects of alprazolam and clonidine on carbon dioxide-induced increases in anxiety ratings in healthy human subjects. Life Sciences 1989, 45: 233-242. PMID: 2503670, DOI: 10.1016/0024-3205(89)90255-5.Peer-Reviewed Original ResearchConceptsHealthy human subjectsClonidine 2 mcg/Pulse rateEffects of alprazolamAnxiety-like effectsHuman subjectsRatings of anxietyOral alprazolamHypotensive effectVentilatory responseMcg/Noradrenergic systemBenzodiazepine receptorsAnxiolytic propertiesNeurobiologic mechanismsClonidineNew drugsAlprazolamAnxiety ratingsSubjective anxietyDrugsAnxietyNormal functioningNeural systemsUseful model system