2021
Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk
Powell SK, O’Shea C, Townsley K, Prytkova I, Dobrindt K, Elahi R, Iskhakova M, Lambert T, Valada A, Liao W, Ho SM, Slesinger PA, Huckins LM, Akbarian S, Brennand KJ. Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk. Molecular Psychiatry 2021, 28: 1970-1982. PMID: 34493831, PMCID: PMC8898985, DOI: 10.1038/s41380-021-01273-0.Peer-Reviewed Original ResearchConceptsInduced dopaminergic neuronsDopaminergic neuronsMidbrain dopaminergic neuron developmentNeuron identityHuman induced pluripotent stem cellsCannabis use disorderDopaminergic neuron developmentAction potential durationGlutamatergic neuronsDopamine synthesisSpontaneous burstsPotential durationUse disordersNeuronal subtypesPsychiatric diseasesBipolar disorderElectrophysiological propertiesDisease riskHyperpolarization potentialPsychiatric disease riskNeuron developmentOscillatory activityNeuronsHeterogenous cell populationsCell populationsCircadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies
Mishra H, Ying N, Luis A, Wei H, Nguyen M, Nakhla T, Vandenburgh S, Alda M, Berrettini W, Brennand K, Calabrese J, Coryell W, Frye M, Gage F, Gershon E, McInnis M, Nievergelt C, Nurnberger J, Shilling P, Oedegaard K, Zandi P, Kelsoe J, Welsh D, McCarthy M. Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies. Molecular Psychiatry 2021, 26: 3383-3394. PMID: 33674753, PMCID: PMC8418615, DOI: 10.1038/s41380-021-01048-7.Peer-Reviewed Original ResearchConceptsNeuronal precursor cellsBipolar disorderCircadian rhythm abnormalitiesRhythm abnormalitiesBD groupCircadian rhythmPatient-derived neuronsMania/hypomaniaExpression of Per2Induced pluripotent stem cellsPER2 protein levelsGlutamatergic neuronsRecurrent episodesBD patientsControl neuronsLithium respondersEffective drugsNeuropsychiatric illnessLithium responsivenessPatient neuronsNeuronsLithium responseProtein levelsRhythm deficitsPrecursor cells
2020
A psychiatric disease-related circular RNA controls synaptic gene expression and cognition
Zimmerman AJ, Hafez AK, Amoah SK, Rodriguez BA, Dell’Orco M, Lozano E, Hartley BJ, Alural B, Lalonde J, Chander P, Webster MJ, Perlis RH, Brennand KJ, Haggarty SJ, Weick J, Perrone-Bizzozero N, Brigman JL, Mellios N. A psychiatric disease-related circular RNA controls synaptic gene expression and cognition. Molecular Psychiatry 2020, 25: 2712-2727. PMID: 31988434, PMCID: PMC7577899, DOI: 10.1038/s41380-020-0653-4.Peer-Reviewed Original ResearchConceptsSynaptic gene expressionCircular RNAsGene expressionAlternative mRNA transcriptsDisease-associated circRNAsHomolog 1Neuronal RNAMRNA transcriptsRNASynaptic expressionAge of onsetMammalian brainCircRNAsPotential involvementDorsolateral prefrontal cortexOrbitofrontal cortexBipolar disorderPrefrontal cortexKnockdownExpressionFrontal cortexSynaptic plasticityNeuronal culturesPsychiatric diseasesMouse orbitofrontal cortex
2018
Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder
McCarthy MJ, Wei H, Nievergelt CM, Stautland A, Maihofer AX, Welsh DK, Shilling P, Alda M, Alliey-Rodriguez N, Anand A, Andreasson OA, Balaraman Y, Berrettini WH, Bertram H, Brennand KJ, Calabrese JR, Calkin CV, Claasen A, Conroy C, Coryell WH, Craig DW, D’Arcangelo N, Demodena A, Djurovic S, Feeder S, Fisher C, Frazier N, Frye MA, Gage FH, Gao K, Garnham J, Gershon ES, Glazer K, Goes F, Goto T, Harrington G, Jakobsen P, Kamali M, Karberg E, Kelly M, Leckband SG, Lohoff F, McInnis MG, Mondimore F, Morken G, Nurnberger JI, Obral S, Oedegaard KJ, Ortiz A, Ritchey M, Ryan K, Schinagle M, Schoeyen H, Schwebel C, Shaw M, Shekhtman T, Slaney C, Stapp E, Szelinger S, Tarwater B, Zandi PP, Kelsoe JR. Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder. Neuropsychopharmacology 2018, 44: 620-628. PMID: 30487653, PMCID: PMC6333516, DOI: 10.1038/s41386-018-0273-8.Peer-Reviewed Original ResearchConceptsBipolar disorderEffects of lithiumMaintenance treatmentBD patientsCircadian rhythmMinority of patientsLithium maintenance treatmentMood stabilizer treatmentSerious mood disorderCircadian rhythm abnormalitiesCircadian rhythm parametersClinical responseCircadian rhythm functionLithium monotherapyClinical trialsMood disordersRhythm abnormalitiesMood symptomsPharmacological effectsPatientsEvening chronotypeStabilizer treatmentCommon genetic variationRhythm parametersMonotherapy
2016
The Pharmacogenomics of Bipolar Disorder study (PGBD): identification of genes for lithium response in a prospective sample
Oedegaard K, Alda M, Anand A, Andreassen O, Balaraman Y, Berrettini W, Bhattacharjee A, Brennand K, Burdick K, Calabrese J, Calkin C, Claasen A, Coryell W, Craig D, DeModena A, Frye M, Gage F, Gao K, Garnham J, Gershon E, Jakobsen P, Leckband S, McCarthy M, McInnis M, Maihofer A, Mertens J, Morken G, Nievergelt C, Nurnberger J, Pham S, Schoeyen H, Shekhtman T, Shilling P, Szelinger S, Tarwater B, Yao J, Zandi P, Kelsoe J. The Pharmacogenomics of Bipolar Disorder study (PGBD): identification of genes for lithium response in a prospective sample. BMC Psychiatry 2016, 16: 129. PMID: 27150464, PMCID: PMC4857276, DOI: 10.1186/s12888-016-0732-x.Peer-Reviewed Original ResearchConceptsLithium monotherapyBipolar disorderLithium responseMechanism of actionClinical managementValproic acidLithium respondersSingle nucleotide polymorphismsMethods/designThis studyCox proportional hazards modelProspective study sampleLarge prospective cohortLarge prospective studiesClinical Global ImpressionInitiation of treatmentMood-stabilizing medicationsBipolar Disorder (STEP-BD) studyProportional hazards modelResults of treatmentCommon psychiatric disordersMEq/L.Genome-wide association studiesClinical relapseProspective cohortRemitting course
2015
Erratum: Differential 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. Erratum: Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature 2015, 530: 242-242. PMID: 26605530, DOI: 10.1038/nature16182.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 Research
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