2022
Matthew J. Friedman, M.D., Ph.D. and His Legacy of Leadership in the Field of Post-traumatic Stress Disorder
Krystal JH, Southwick SM, Girgenti MJ. Matthew J. Friedman, M.D., Ph.D. and His Legacy of Leadership in the Field of Post-traumatic Stress Disorder. Psychiatry 2022, 85: 161-170. PMID: 35588483, DOI: 10.1080/00332747.2022.2068931.Peer-Reviewed Original Research
2021
Posttraumatic Stress Disorder Brain Transcriptomics: Convergent Genomic Signatures Across Biological Sex
Wang J, Zhao H, Girgenti MJ. Posttraumatic Stress Disorder Brain Transcriptomics: Convergent Genomic Signatures Across Biological Sex. Biological Psychiatry 2021, 91: 6-13. PMID: 33840456, DOI: 10.1016/j.biopsych.2021.02.012.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBrainFemaleGenomicsHumansMaleSex CharacteristicsSex FactorsStress Disorders, Post-TraumaticTranscriptomeConceptsPosttraumatic stress disorderConvergent genomic signaturesSpecific cell typesGene regulationGenomic regulationGenomic signaturesGenomic technologiesMolecular determinantsCell typesBrains of malesMolecular effectsGABAergic signalingMolecular pathologyImmune functionPTSD brainsSex impactRegulationStress disorderStructural differencesEffects of sex
2020
Transcriptomic organization of the human brain in post-traumatic stress disorder
Girgenti MJ, Wang J, Ji D, Cruz DA, Stein M, Gelernter J, Young K, Huber B, Williamson D, Friedman M, Krystal J, Zhao H, Duman R. Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience 2020, 24: 24-33. PMID: 33349712, DOI: 10.1038/s41593-020-00748-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBrain ChemistryCohort StudiesDepressive Disorder, MajorFemaleGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterneuronsMaleMiddle AgedNerve Tissue ProteinsSex CharacteristicsStress Disorders, Post-TraumaticTranscriptomeYoung AdultConceptsGenome-wide association studiesSignificant gene networksDifferential gene expressionSystems-level evidenceSignificant genetic liabilityMajor depressive disorder cohortGene networksTranscriptomic organizationTranscriptomic landscapeDownregulated setsGenomic networksGene expressionAssociation studiesMolecular determinantsExtensive remodelingGenotype dataSexual dimorphismSignificant divergenceMolecular profileNetwork analysisELFN1TranscriptsDimorphismPostmortem tissueDivergenceStress and Its Impact on the Transcriptome
Girgenti MJ, Pothula S, Newton SS. Stress and Its Impact on the Transcriptome. Biological Psychiatry 2020, 90: 102-108. PMID: 33637305, PMCID: PMC8213869, DOI: 10.1016/j.biopsych.2020.12.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainFemaleHumansMaleStress Disorders, Post-TraumaticStress, PsychologicalTranscriptomeConceptsTranscriptomic dysregulationMajor gene expression changesGene expression changesDevelopmental time pointsAnimal modelsGenomic studiesNeuropsychiatric disordersTranscriptomic methodsAnimal kingdomComparable animal modelsGene expressionExpression changesEarly life stressPhenotypic signaturesSex-specific changesTransgenerational impactTranscriptomeSingle cellsEntire brain regionsPowerful approachDiseased brainBrain regionsChronic stressMolecular profileSame disorderCortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder
Stone LA, Girgenti MJ, Wang J, Ji D, Zhao H, Krystal JH, Duman R. Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder. The International Journal Of Neuropsychopharmacology 2020, 24: 118-129. PMID: 32951025, PMCID: PMC8611677, DOI: 10.1093/ijnp/pyaa072.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBody Mass IndexFemaleGene Regulatory NetworksGhrelinHumansMaleMiddle AgedNeuropeptide YOrexinsPrefrontal CortexStress Disorders, Post-TraumaticTranscriptomeConceptsUpstream regulatorGene co-expression network analysisCo-expression network analysisFunctional genomic studiesPutative upstream regulatorsIngenuity Pathway Analysis softwarePathway Analysis softwarePathway annotationGenomic studiesTranscriptomic modulesTranscriptomic dataTranscriptomic alterationsGene expressionPTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imaging
2018
Molecular and cellular studies of PTSD: Postmortem transcriptome analysis and novel therapeutic targets
Duman RS, Girgenti MJ. Molecular and cellular studies of PTSD: Postmortem transcriptome analysis and novel therapeutic targets. Journal Of Neuroscience Research 2018, 97: 292-299. PMID: 30136735, DOI: 10.1002/jnr.24306.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutopsyCerebral CortexExtinction, PsychologicalFearGene Expression ProfilingHumansMemoryStress Disorders, Post-TraumaticConceptsFear memoryPrefrontal cortexPTSD patientsFear memory processesNeurobiology of PTSDMemory processesInhibitory controlNeurobiological underpinningsPFC subregionsPTSD subjectsPTSDMemory studiesBrain regionsMemorySpecific gene expression alterationsNovel therapeutic targetPostmortem brain tissueEfficacious treatmentNeurobiologySynaptic alterationsSynapse numberEarlier findingsRodent modelsTherapeutic targetGene expression alterations
2017
Transcriptome Alterations in Posttraumatic Stress Disorder
Girgenti MJ, Duman RS. Transcriptome Alterations in Posttraumatic Stress Disorder. Biological Psychiatry 2017, 83: 840-848. PMID: 29128043, DOI: 10.1016/j.biopsych.2017.09.023.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderNext-generation sequencing technologiesAberrant gene expressionGene expression changesAmount of transcriptsGene expression studiesGene profiling studiesAlternative splicingTranscriptome alterationsTranscriptomic technologiesRNA sequencingSequencing technologiesTranscript identificationExpression studiesGene expressionExpression changesStress disorderBlood of patientsCellular mechanismsPeripheral blood cellsProfiling studiesHuman peripheral bloodPeripheral bloodLifetime prevalenceGeneral populationMolecular and Cellular Effects of Traumatic Stress: Implications for PTSD
Girgenti MJ, Hare BD, Ghosal S, Duman RS. Molecular and Cellular Effects of Traumatic Stress: Implications for PTSD. Current Psychiatry Reports 2017, 19: 85. PMID: 28944401, PMCID: PMC5907804, DOI: 10.1007/s11920-017-0841-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainGenomicsGlucocorticoidsHumansInflammationRatsSignal TransductionStress Disorders, Post-TraumaticConceptsPathophysiology of PTSDPreclinical modelsReviewPosttraumatic stress disorderPeripheral blood studiesMolecular changesGlucocorticoid receptor signalingPrimary brain regionsPeripheral bloodInflammatory systemBlood studiesGlucocorticoid signalingHuman studiesPTSD patientsMolecular alterationsBrain regionsStress disorderAltered gene expressionPathophysiologyReceptor signalingCellular pathophysiologyNeurobiological determinantsCellular effectsMechanistic evidencePTSDPatientsAltered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence
Holmes SE, Girgenti MJ, Davis MT, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Southwick S, Duman RS, Carson RE, Krystal JH, Esterlis I, Friedman M, Kowall N, Brady C, McKee A, Stein T, Huber B, Kaloupek D, Alvarez V, Benedek D, Ursano R, Williamson D, Cruz D, Young K, Duman R, Krystal J, Mash D, Hardegree M, Serlin G. Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 8390-8395. PMID: 28716937, PMCID: PMC5547601, DOI: 10.1073/pnas.1701749114.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMGluR5 availabilityPositron emission tomographyGlutamate systemMetabotropic glutamate receptor 5Treatment of PTSDHuman posttraumatic stress disorderGlutamate receptor 5Mechanism-based treatmentsExpression of FKBP5Promising treatment targetHuman postmortem tissueTargeted pharmacological treatmentStress psychopathologyPharmacological treatmentExpression of proteinsReceptor 5MGluR5Treatment targetsPostmortem tissueEmission tomographyStress disorderPostmortem samplesPromising targetDisorders
2016
Ketamine accelerates fear extinction via mTORC1 signaling
Girgenti MJ, Ghosal S, LoPresto D, Taylor JR, Duman RS. Ketamine accelerates fear extinction via mTORC1 signaling. Neurobiology Of Disease 2016, 100: 1-8. PMID: 28043916, PMCID: PMC5907920, DOI: 10.1016/j.nbd.2016.12.026.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderMedial prefrontal cortexTreatment of PTSDFear conditioningRetrieval of extinctionExpression of extinctionActivity-dependent effectsTraumatic memoriesStress disorderExtinction exposurePTSD patientsPrefrontal cortexEffects of ketamineGlutamate NMDA receptor antagonistSymptom severityConditioningInfusion of ketamineExtinctionCuesRodent modelsMemoryKetamine administrationReceptor antagonistPresent studyNMDA receptor antagonist