2023
CpH methylome analysis in human cortical neurons identifies novel gene pathways and drug targets for opioid use disorder
Nagamatsu S, Rompala G, Hurd Y, Núñez-Rios D, Montalvo-Ortiz J, Group T, Alvarez V, Benedek D, Che A, Cruz D, Davis D, Girgenti M, Hoffman E, Holtzheimer P, Huber B, Kaye A, Krystal J, Labadorf A, Keane T, Logue M, McKee A, Marx B, Mash D, Miller M, Noller C, JM-O, Scott W, Schnurr P, Stein T, Ursano R, Williamson D, Wolf E, Young K. CpH methylome analysis in human cortical neurons identifies novel gene pathways and drug targets for opioid use disorder. Frontiers In Psychiatry 2023, 13: 1078894. PMID: 36745154, PMCID: PMC9892724, DOI: 10.3389/fpsyt.2022.1078894.Peer-Reviewed Original ResearchOpioid use disorderOrbital frontal cortexDNA methylationKEGG enrichment analysisUse disordersMCPH lociTreatment of OUDGene OntologyEnrichment analysisOpioid-related drugsCpG sitesDrug targetsOxidative bisulfite sequencingImportant biological pathwaysDrug interaction analysisDrug-gene interaction databaseNervous system developmentSmoking statusBrain BankCortical neuronsFrontal cortexNeuronal nucleiHuman studiesGene regulationMethylome analysis
2021
Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants
Thompson SL, Gianessi CA, O'Malley SS, Cavallo DA, Shi JM, Tetrault JM, DeMartini KS, Gueorguieva R, Pittman B, Krystal JH, Taylor JR, Krishnan-Sarin S. Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants. Frontiers In Psychiatry 2021, 12: 709559. PMID: 34531767, PMCID: PMC8438169, DOI: 10.3389/fpsyt.2021.709559.Peer-Reviewed Original ResearchNMDA receptorsSrc/FynAlcohol consumptionEffect of saracatinibVehicle 2 hChronic alcohol useDays of treatmentDSM-IV criteriaMore effective treatmentsNumber of drinksGlutamatergic systemAdditional drinkAlcohol drinkingAdditional dosesEthanol exposureEffective treatmentNR2B subunitAlcohol abuseHuman studiesPriming drinkAlcohol cravingSaracatinibDrinking paradigmNovel pharmacotherapeuticsHuman participants
2020
Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence
Hillmer AT, Angarita GA, Esterlis I, Anderson JM, Nabulsi N, Lim K, Ropchan J, Carson RE, Krystal JH, Malley S, Cosgrove KP. Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence. Neuropsychopharmacology 2020, 46: 380-385. PMID: 32919411, PMCID: PMC7852514, DOI: 10.1038/s41386-020-00856-9.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsSmoking statusAlcohol abstinenceEarly abstinenceMGlu5 receptor negative allosteric modulatorReceptor negative allosteric modulatorChronic alcohol useCortical brain regionsAlcohol use disorderEmission Tomography ImagingPositron emission tomography (PET) imagingNegative allosteric modulatorsDSM-5 criteriaCue-induced reinstatementHealthy controlsPreclinical literatureGlutamate systemPreclinical modelsHuman evidenceReceptor drugsPET scansUse disordersHuman studiesReceptor availabilityStudy duration
2016
Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies
Averill LA, Purohit P, Averill CL, Boesl MA, Krystal JH, Abdallah CG. Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies. Neuroscience Letters 2016, 649: 147-155. PMID: 27916636, PMCID: PMC5482215, DOI: 10.1016/j.neulet.2016.11.064.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPsychiatric disordersStress-related psychiatric disordersAlternative pharmacologic treatmentsPutative neurobiological underpinningsGlutamate-modulating agentsTrauma-related disordersGlutamatergic abnormalitiesGlutamate dysregulationPharmacologic treatmentPharmacologic interventionsGlutamatergic functionGlutamate neurotransmissionMillions of individualsHuman studiesCardinal featuresStress disorderDisordersNeurobiological underpinningsRelated future directionsEvidenceChronicDysfunctionNeurotransmissionSubject data
2001
NMDA receptor regulation of memory and behavior in humans
Newcomer J, Krystal J. NMDA receptor regulation of memory and behavior in humans. Hippocampus 2001, 11: 529-542. PMID: 11732706, DOI: 10.1002/hipo.1069.Peer-Reviewed Original ResearchConceptsNMDA receptor hypofunctionReceptor hypofunctionN-methyl-D-aspartate (NMDA) receptor hypofunctionNMDA receptor antagonist drugsNMDA receptor systemAge-related decreaseNMDA receptor regulationReceptor antagonist drugsClinical syndromeNeuropathological featuresNMDA antagonistsNMDA receptorsNeurotoxic processesAntagonist drugsAdult brainHypofunctionBehavioral dysfunctionHuman studiesRange of effectsReceptor regulationReceptor systemBrain functionBrain ageAdverse effectsDisease conditions
1988
Biological Mechanisms in Posttraumatic Stress Disorder Relevance for Substance Abuse
Kosten T, Krystal J. Biological Mechanisms in Posttraumatic Stress Disorder Relevance for Substance Abuse. Recent Developments In Alcoholism 1988, 6: 49-68. PMID: 3283864, DOI: 10.1007/978-1-4615-7718-8_3.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderSubstance abuseHuman studiesEndogenous opioid systemCentral catecholaminesOpioid systemBrain catecholaminesEmotional response modelsTherapeutic approachesAnimal studiesSignificant biological contributionStress disorderNonhuman primatesBehavioral correlatesCatecholaminesRelevant animalBiological mechanismsRecent studiesAbuseIndirect measureSyndromeIncidenceStudy