2025
Single-cell transcriptomic and chromatin dynamics of the human brain in PTSD
Hwang A, Skarica M, Xu S, Coudriet J, Lee C, Lin L, Terwilliger R, Sliby A, Wang J, Nguyen T, Li H, Wu M, Dai Y, Duan Z, Srinivasan S, Zhang X, Lin Y, Cruz D, Deans P, Huber B, Levey D, Glausier J, Lewis D, Gelernter J, Holtzheimer P, Friedman M, Gerstein M, Sestan N, Brennand K, Xu K, Zhao H, Krystal J, Young K, Williamson D, Che A, Zhang J, Girgenti M. Single-cell transcriptomic and chromatin dynamics of the human brain in PTSD. Nature 2025, 643: 744-754. PMID: 40533550, PMCID: PMC12267058, DOI: 10.1038/s41586-025-09083-y.Peer-Reviewed Original ResearchPost-traumatic stress disorderPrefrontal cortexDorsolateral prefrontal cortexHuman prefrontal cortexTraumatic stress responseHuman brainDepressive disorderStress disorderTrauma exposureCell type-specific contextRegulatory mechanismsGABAergic transmissionCell-type clusteringCell type-specific mannerMolecular regulatory mechanismsGlucocorticoid signalingGene expression changesChromatin dynamicsCredible variantsDisordersTranscriptional regulationEpigenetic dataCortexPersistent effectsPolygenic disorderThe left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes
Gui Y, Zhou G, Cui S, Li H, Lu H, Zhao H. The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes. Translational Psychiatry 2025, 15: 17. PMID: 39843917, PMCID: PMC11754786, DOI: 10.1038/s41398-025-03223-8.Peer-Reviewed Original ResearchConceptsLeft amygdala volumePolygenic risk scoresLeft amygdalaSex differencesBrain volumeMental disordersAmygdala volumeBrain anatomyEffect of polygenic risk scoresStudy of sex differencesExamined sex differencesPsychiatric Genomics ConsortiumMechanisms of sex differencesSex-specific genetic correlationsGenetic correlation analysisAmygdalaStructural MRI volumesSexually-dimorphicGenetic correlationsBrainDisordersRNA-seq dataGenomics ConsortiumCell-type compositionKnowledge of genetic basis
2024
Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood
Daskalakis N, Iatrou A, Chatzinakos C, Jajoo A, Snijders C, Wylie D, DiPietro C, Tsatsani I, Chen C, Pernia C, Soliva-Estruch M, Arasappan D, Bharadwaj R, Collado-Torres L, Wuchty S, Alvarez V, Dammer E, Deep-Soboslay A, Duong D, Eagles N, Huber B, Huuki L, Holstein V, Logue M, Lugenbühl J, Maihofer A, Miller M, Nievergelt C, Pertea G, Ross D, Sendi M, Sun B, Tao R, Tooke J, Wolf E, Zeier Z, Berretta S, Champagne F, Hyde T, Seyfried N, Shin J, Weinberger D, Nemeroff C, Kleinman J, Ressler K, Nievergelt C, Maihofer A, Atkinson E, Chen C, Choi K, Coleman J, Daskalakis N, Duncan L, Polimanti R, Aaronson C, Amstadter A, Andersen S, Andreassen O, Arbisi P, Ashley-Koch A, Austin S, Avdibegoviç E, Babić D, Bacanu S, Baker D, Batzler A, Beckham J, Belangero S, Benjet C, Bergner C, Bierer L, Biernacka J, Bierut L, Bisson J, Boks M, Bolger E, Brandolino A, Breen G, Bressan R, Bryant R, Bustamante A, Bybjerg-Grauholm J, Bækvad-Hansen M, Børglum A, Børte S, Cahn L, Calabrese J, Caldas-de-Almeida J, Chatzinakos C, Cheema S, Clouston S, Colodro-Conde L, Coombes B, Cruz-Fuentes C, Dale A, Dalvie S, Davis L, Deckert J, Delahanty D, Dennis M, Desarnaud F, DiPietro C, Disner S, Docherty A, Domschke K, Dyb G, Kulenović A, Edenberg H, Evans A, Fabbri C, Fani N, Farrer L, Feder A, Feeny N, Flory J, Forbes D, Franz C, Galea S, Garrett M, Gelaye B, Gelernter J, Geuze E, Gillespie C, Goleva S, Gordon S, Goçi A, Grasser L, Guindalini C, Haas M, Hagenaars S, Hauser M, Heath A, Hemmings S, Hesselbrock V, Hickie I, Hogan K, Hougaard D, Huang H, Huckins L, Hveem K, Jakovljević M, Javanbakht A, Jenkins G, Johnson J, Jones I, Jovanovic T, Karstoft K, Kaufman M, Kennedy J, Kessler R, Khan A, Kimbrel N, King A, Koen N, Kotov R, Kranzler H, Krebs K, Kremen W, Kuan P, Lawford B, Lebois L, Lehto K, Levey D, Lewis C, Liberzon I, Linnstaedt S, Logue M, Lori A, Lu Y, Luft B, Lupton M, Luykx J, Makotkine I, Maples-Keller J, Marchese S, Marmar C, Martin N, Martínez-Levy G, McAloney K, McFarlane A, McLaughlin K, McLean S, Medland S, Mehta D, Meyers J, Michopoulos V, Mikita E, Milani L, Milberg W, Miller M, Morey R, Morris C, Mors O, Mortensen P, Mufford M, Nelson E, Nordentoft M, Norman S, Nugent N, O'Donnell M, Orcutt H, Pan P, Panizzon M, Pathak G, Peters E, Peterson A, Peverill M, Pietrzak R, Polusny M, Porjesz B, Powers A, Qin X, Ratanatharathorn A, Risbrough V, Roberts A, Rothbaum A, Rothbaum B, Roy-Byrne P, Ruggiero K, Rung A, Runz H, Rutten B, de Viteri S, Salum G, Sampson L, Sanchez S, Santoro M, Seah C, Seedat S, Seng J, Shabalin A, Sheerin C, Silove D, Smith A, Smoller J, Sponheim S, Stein D, Stensland S, Stevens J, Sumner J, Teicher M, Thompson W, Tiwari A, Trapido E, Uddin M, Ursano R, Valdimarsdóttir U, Van Hooff M, Vermetten E, Vinkers C, Voisey J, Wang Y, Wang Z, Waszczuk M, Weber H, Wendt F, Werge T, Williams M, Williamson D, Winsvold B, Winternitz S, Wolf C, Wolf E, Xia Y, Xiong Y, Yehuda R, Young K, Young R, Zai C, Zai G, Zervas M, Zhao H, Zoellner L, Zwart J, deRoon-Cassini T, van Rooij S, van den Heuvel L, Stein M, Ressler K, Koenen K. Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood. Science 2024, 384: eadh3707. PMID: 38781393, PMCID: PMC11203158, DOI: 10.1126/science.adh3707.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPosttraumatic stress disorderMedial prefrontal cortexStudies of posttraumatic stress disorderStress-related disordersHippocampal dentate gyrusDorsolateral PFCPrefrontal cortexDepressive disorderStress disorderBrain regionsCentral nucleusDentate gyrusGenome-wide association studiesSynaptic regulationMolecular pathologyMultiomics studiesStress hormonesGene network analysisDisordersCell typesNon-neuronal cell typesSingle nucleus RNA sequencingGenomic structureFine-mapping
2022
Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults
Gui Y, Zhou X, Wang Z, Zhang Y, Wang Z, Zhou G, Zhao Y, Liu M, Lu H, Zhao H. Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults. Translational Psychiatry 2022, 12: 347. PMID: 36028495, PMCID: PMC9418275, DOI: 10.1038/s41398-022-02041-6.Peer-Reviewed Original ResearchConceptsCognitive functionFluid intelligenceCognitive traitsAdolescent Brain Cognitive Development (ABCD) studyPsychiatric disordersCognitive Development StudyMediation effectMost psychiatric disordersPolygenic risk scoresBrain functionBrain structuresBrain imagingEarly etiologySex differencesDevelopment studiesPsychiatric traitsChildrenIntelligenceDisordersSchizophreniaGenetic riskAdultsTraitsCognitionAutism
2021
Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder
Mundy J, Hübel C, Gelernter J, Levey D, Murray RM, Skelton M, Stein MB, Maihofer A, Nievergelt C, Baker D, Risborough V, Calabrese J, Galea S, Stein D, Koen N, Dalvie S, Aiello A, Roberts A, Koenen K, Solovieff N, Kranzler H, Zhao H, Gelernter J, Farrer L, Johnson E, Rice J, Bierut L, Saccone N, McFarlane A, Forbes D, Silove D, O'Donnell M, Bryant R, van Hooff M, Sponheim S, Disner S, Pietrzak R, Chen C, Smoller J, Stein M, Ursano R, Kessler R, Junglen A, Delahanty D, Amstadter A, Sheerin C, Ruggiero K, McLaughlin K, Peverill M, Caldas-de-Almeida J, Austin S, Gelaye B, Williams M, Sanchez S, Franz C, Panizzon M, Lyons M, Kremen W, Andreassen O, Dale A, Rutten B, Vinkers C, Schijven D, Geuze E, Vermetten E, Luykx J, Boks M, Ashley-Koch A, Beckham J, Garrett M, Hauser M, Dennis M, Kimbrel N, Qin X, Karstoft K, Andersen S, Borglum A, Hougaard D, Bybjerg-Grauholm J, Duncan L, Bµkvad-Hansen M, Nordentoft M, Mors O, Mortensen P, Werge T, Thompson W, Wang Y, Heath A, Nelson E, Martin N, Gordon S, Wolf E, Logue M, Miller M, McGlinchey R, Milberg W, Erbes C, Polusny M, Arbisi P, Peterson A, Williamson D, Young K, Maurer D, Rothbaum A, Zoellner L, Mavissakalian M, Feeny N, Roy-Byrne P, Rothbaum B, Maples-Keller J, Khan A, Wolff J, Lebois L, Teicher M, Kaufman M, Winternitz S, Bolger E, Seligowski A, Orcutt H, Evans A, Lugonja B, Lewis C, Jones I, Bisson J, McLean S, Linnstaedt S, Peters E, Rung A, Trapido E, Brashear M, Lori A, Smith A, Bradley B, Gillespie C, Guffanti G, Ressler K, Almli L, Jovanovic T, Bustamante A, Uddin M, van den Heuvel L, Seedat S, Hemmings S, Uka A, Kulenovic A, Wolf C, Babic D, Avdibegovic E, Deckert J, Domschke K, Jakovljevic M, Marmar C, Flory J, Jett M, Yehuda R, Hammamieh R, King A, Liberzon I, Seng J, Morris C, Mehta D, Voisey J, Lawford B, Young R, McLeay S, Daskalakis N, Norman S, Wang Z, Breen G, Coleman J, Klengel T, Torres K, Choi K, Levey D, Polimanti R, Atkinson E, Martin A, Neale B, Daly M, Ripke S, Ratanatharathorn A, Provost A, Haas M, Stevens J, Morey R, Harnal S, Mortensen P, Seedat S, Sumner J, Vassos E, Breen G, Coleman J. Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder. Psychological Medicine 2021, 52: 3975-3984. PMID: 34085609, PMCID: PMC8962503, DOI: 10.1017/s0033291721000830.Peer-Reviewed Original ResearchRecurrent major depressive disorderMajor depressive disorderPosttraumatic stress disorderSingle-episode major depressive disorderDepressive disorderTrauma exposureStress disorderPsychological trauma exposureLifetime major depressive disorderTrauma sensitivityGenetic loadingUK Biobank participantsKey risk factorsMental health consequencesRisk factorsMillion Veteran ProgramPolygenic risk scoresRisk scoreGenetic overlapHealth consequencesBiobank participantsTraumaDisordersVeteran ProgramPsychiatric Genomics Consortium
2018
Spatiotemporal transcriptomic divergence across human and macaque brain development
Zhu Y, Sousa AMM, Gao T, Skarica M, Li M, Santpere G, Esteller-Cucala P, Juan D, Ferrández-Peral L, Gulden FO, Yang M, Miller DJ, Marques-Bonet T, Imamura Kawasawa Y, Zhao H, Sestan N. Spatiotemporal transcriptomic divergence across human and macaque brain development. Science 2018, 362 PMID: 30545855, PMCID: PMC6900982, DOI: 10.1126/science.aat8077.Peer-Reviewed Original ResearchConceptsBrain developmentHuman nervous system developmentHuman brain developmentNervous system developmentPostnatal patternSingle-cell transcriptomic dataSpatiotemporal transcriptional regulationBrain regionsNeuropsychiatric disordersLate fetalPrefrontal cortexTranscriptomic programsHuman dataTranscriptomic divergenceTranscriptional regulationTranscriptomic differencesAutism spectrum disorderTranscriptomic dataDisordersTranscriptomic patternsSpectrum disorderIntegrative analysisPathogenesis
2015
Pervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS
Wang Q, Yang C, Gelernter J, Zhao H. Pervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS. Human Genetics 2015, 134: 1195-1209. PMID: 26340901, PMCID: PMC4630076, DOI: 10.1007/s00439-015-1596-8.Peer-Reviewed Original ResearchMeSH KeywordsArthritis, RheumatoidCentral Nervous SystemCrohn DiseaseGenetic PleiotropyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmune System DiseasesMental DisordersNerve Tissue ProteinsOrgan SpecificityPolymorphism, Single NucleotideQuantitative Trait LociSchizophreniaSystems IntegrationConceptsImmune disordersPsychiatric disordersCrohn's diseaseDisorder pairsMHC regionPervasive pleiotropyIntegrative analysisGenome-wide association studiesImmune dysregulationImmunological mechanismsTreatment strategiesTraits/diseasesEpidemiological observationsPsychiatric diseasesBrain disordersSame effect directionDiseaseDisordersGenomic regionsRealm of psychiatryMost allelesStrong pleiotropyAnnotation resourcesChromosome 6Association studies
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