2024
Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission
Stern S, Zhang L, Wang M, Wright R, Rosh I, Hussein Y, Stern T, Choudhary A, Tripathi U, Reed P, Sadis H, Nayak R, Shemen A, Agarwal K, Cordeiro D, Peles D, Hang Y, Mendes A, Baul T, Roth J, Coorapati S, Boks M, McCombie W, Hulshoff Pol H, Brennand K, Réthelyi J, Kahn R, Marchetto M, Gage F. Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission. Molecular Psychiatry 2024, 1-15. PMID: 38704507, DOI: 10.1038/s41380-024-02561-1.Peer-Reviewed Original ResearchCo-twinSchizophrenia patientsMonozygotic twinsHippocampal synaptic deficitsHealthy twinsSynapse-related genesDepressive disorderPsychiatric disordersSchizophreniaControl twinsTwin pairsSynaptic activitySynaptic deficitsTwin siblingsNeurophysiological abnormalitiesGroup of patientsSynaptic transmissionDiscordant twinsDisordersHippocampal neuronsNeuronsReprogrammed iPSCsIPSC modelsPatientsSiblings
2022
A bidirectional competitive interaction between circHomer1 and Homer1b within the orbitofrontal cortex regulates reversal learning
Hafez A, Zimmerman A, Papageorgiou G, Chandrasekaran J, Amoah S, Lin R, Lozano E, Pierotti C, Dell'Orco M, Hartley B, Alural B, Lalonde J, Esposito J, Berretta S, Squassina A, Chillotti C, Voloudakis G, Shao Z, Fullard J, Brennand K, Turecki G, Roussos P, Perlis R, Haggarty S, Perrone-Bizzozero N, Brigman J, Mellios N. A bidirectional competitive interaction between circHomer1 and Homer1b within the orbitofrontal cortex regulates reversal learning. Cell Reports 2022, 38: 110282. PMID: 35045295, PMCID: PMC8809079, DOI: 10.1016/j.celrep.2021.110282.Peer-Reviewed Original ResearchConceptsImportance of circRNAsRNA-binding proteinSynaptic gene expressionCircular RNAsGene expressionOrbitofrontal cortexCompetitive interactionsComplete rescuePsychiatric disordersKnockdownSynaptic expressionMechanistic insightsBrain functionMRNAHomer1bBehavioral flexibilityNeuronal culturesExpressionBiogenesisCircRNAsRNAProteinRegulatesReversal learningDisorders
2015
Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders
Brennand KJ, Marchetto MC, Benvenisty N, Brüstle O, Ebert A, Belmonte J, Kaykas A, Lancaster MA, Livesey FJ, McConnell MJ, McKay RD, Morrow EM, Muotri AR, Panchision DM, Rubin LL, Sawa A, Soldner F, Song H, Studer L, Temple S, Vaccarino FM, Wu J, Vanderhaeghen P, Gage FH, Jaenisch R. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders. Stem Cell Reports 2015, 5: 933-945. PMID: 26610635, PMCID: PMC4881284, DOI: 10.1016/j.stemcr.2015.10.011.Peer-Reviewed Original ResearchDifferential responses to lithium in hyperexcitable neurons from patients with bipolar disorder
Mertens J, Wang Q, Kim Y, Yu D, Pham S, Yang B, Zheng Y, Diffenderfer K, Zhang J, Soltani S, Eames T, Schafer S, Boyer L, Marchetto M, Nurnberger J, Calabrese J, Oedegaard K, McCarthy M, Zandi P, Alda M, Nievergelt C, Mi S, Brennand K, Kelsoe J, Gage F, Yao J. Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature 2015, 527: 95-99. PMID: 26524527, PMCID: PMC4742055, DOI: 10.1038/nature15526.Peer-Reviewed Original ResearchCharacterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells
Lee I, Carvalho C, Douvaras P, Ho S, Hartley B, Zuccherato L, Ladran I, Siegel A, McCarthy S, Malhotra D, Sebat J, Rapoport J, Fossati V, Lupski J, Levy D, Brennand K. Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells. Schizophrenia 2015, 1: 15019. PMID: 26985448, PMCID: PMC4789165, DOI: 10.1038/npjschz.2015.19.Peer-Reviewed Original ResearchClinical outcomesCNTNAP2 expressionHiPSC neural progenitor cellsDiscordant clinical outcomesHiPSC-derived neuronsOligodendrocyte precursor cellsNeural progenitor cellsContactin-associated proteinHuman neuronsAnimal modelsClinical settingGenetic deletionExpression patternsNeural cellsProgenitor cellsLarge heterozygous deletionsNeurodevelopmental disordersPrecursor cellsDisordersComplex disorderHeterozygous deletionSignificant differencesNeuronsStem cellsExon 14From “Directed Differentiation” to “Neuronal Induction”: Modeling Neuropsychiatric Disease
Ho S, Topol A, Brennand K. From “Directed Differentiation” to “Neuronal Induction”: Modeling Neuropsychiatric Disease. Biomarker Insights 2015, 10s1: bmi.s20066. PMID: 26045654, PMCID: PMC4444490, DOI: 10.4137/bmi.s20066.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNeuronal inductionSomatic cell reprogrammingNeuropsychiatric diseasesPsychiatric disordersPluripotent stem cell (iPSC) technologyCell reprogrammingDirected DifferentiationMost neurological diseasesStem cell technologyHuman postmortem samplesFunction of neuronsPolygenic originHuman neuronsDisease onsetAnimal modelsNeurological diseasesDisease initiationPostmortem samplesDiseaseNeuronsDifferentiationPrimary causeLimitless numberDisordersAberrant behavior
2012
Modeling psychiatric disorders at the cellular and network levels
Brennand K, Simone A, Tran N, Gage F. Modeling psychiatric disorders at the cellular and network levels. Molecular Psychiatry 2012, 17: 1239-1253. PMID: 22472874, PMCID: PMC3465628, DOI: 10.1038/mp.2012.20.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCell-based studiesPluripotent stem cell-derived neuronsStem cell-derived neuronsLive human neuronsCell-derived neuronsPsychiatric disordersBasic phenotypesGenetic backgroundHuman neuronsClinical symptomsComplex arrayBipolar disorderBrain regionsDisease statesNeuronsSingle neuronsDisordersLimitless numberAutism spectrum disorderSpectrum disorderPhenotypeFibroblastsPatientsSymptomsSchizophrenia