Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder
Open accessAbstract
Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide. Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity. Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models, such as reduced glial cell number in the prefrontal cortex of patients, upregulated activities of the protein kinase A and C pathways and changes in neurotransmission. However, the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease. Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge. The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach. Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder. Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca(2+) imaging, we have observed hyperactive action-potential firing. This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment. Therefore, hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.
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Neurons from people with bipolar disorder were hyperexcitable and their activity was selectively modified by in vitro lithium in accordance with clinical response.
“The neurons from people with BD were hyperexcitable and their activity was selectively modified by in vitro lithium in accordance with clinical response.419”
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Cites
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364 · see citing works
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221 · see citing works
Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in neurodegenerative diseases
Chen, H., & Chan, D. C. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp326 · Cited by 1,455 · see citing works
Modelling schizophrenia using human induced pluripotent stem cells
Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y., Chen, G., Yu, D., et al. (2011) · Nature · doi:10.1038/nature09915 · Cited by 1,375 · see citing works
Self-citationMarchetto, M. C. N., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., Chen, G., Gage, F. H., & Muotri, A. R. (2010) · Cell · doi:10.1016/j.cell.2010.10.016 · Cited by 1,329 · see citing works
Self-citationHigh-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision
Grewe, B. F., Langer, D., Kasper, H., Kampa, B. M., & Helmchen, F. (2010) · Nature Methods · doi:10.1038/nmeth.1453 · Cited by 525 · see citing works
Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia
Brennand, K., Savas, J. N., Kim, Y., Tran, N., Simone, A. D., Hashimoto‐Torii, K., Beaumont, K. G., Kim, H., Topol, A., Ladran, I., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.22 · Cited by 406 · see citing works
Self-citationDopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder
Berk, M., Dodd, S., Kauer‐Sant’Anna, M., Malhi, G. S., Bourin, M., Kapczinski, F., & Norman, T. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2007.01058.x · Cited by 396 · see citing works
Yuan, L., Adams, J. P., Swank, M. W., Sweatt, J. D., & Johnston, D. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-12-04860.2002 · Cited by 314 · see citing works
Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells
Yu, D. X., Giorgio, F. P. D., Yao, J., Marchetto, M. C., Brennand, K., Wright, R., Mei, A., McHenry, L. K., Lisuk, D., Grasmick, J. M., et al. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.01.009 · Cited by 264 · see citing works
Self-citationMotile axonal mitochondria contribute to the variability of presynaptic strength
Sun, T., Qiao, H., Pan, P.-Y., Chen, Y., & Sheng, Z.-H. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.040 · Cited by 263 · see citing works
Psychiatric Comorbidity in 36 Adults with Mitochondrial Cytopathies
Fattal, O., Link, J. N., Quinn, K. M., Cohen, B. H., & Franco, K. S. N. (2007) · CNS Spectrums · doi:10.1017/s1092852900015303 · Cited by 220 · see citing works
Bertolino, A., Frye, M. A., Callicott, J. H., Mattay, V. S., Rakow‐Penner, R., Shelton, J. R., Post, R. M., & Weinberger, D. R. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01911-x · Cited by 201 · see citing works
Mortality in affective disorder
Sharma, R., & Markar, H. (1994) · Journal of Affective Disorders · doi:10.1016/0165-0327(94)90112-0 · Cited by 159 · see citing works
Lower Concentration of Hippocampal N-Acetylaspartate in Familial Bipolar I Disorder
Deicken, R. F., Pegues, M., Anzalone, S., Feiwell, R., & Soher, B. J. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.5.873 · Cited by 153 · see citing works
Serotonin and bipolar disorder
Mahmood, T., & Silverstone, T. (2001) · Journal of Affective Disorders · doi:10.1016/s0165-0327(00)00226-3 · Cited by 126 · see citing works
Bipolar disorder: from genes to behavior pathways
Martinowich, K., Schloesser, R. J., & Manji, H. K. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37703 · Cited by 123 · see citing works
Immature Dentate Gyrus: An Endophenotype of Neuropsychiatric Disorders
Hagihara, H., Takao, K., Walton, N. M., Matsumoto, M., & Miyakawa, T. (2013) · Neural Plasticity · doi:10.1155/2013/318596 · Cited by 123 · see citing works
Decreased hippocampal NMDA, but not kainate or AMPA receptors in bipolar disorder
Scarr, E., Pavey, G., Sundram, S., Mackinnon, A. J., & Dean, B. (2003) · Bipolar Disorders · doi:10.1034/j.1399-5618.2003.00024.x · Cited by 121 · see citing works
Coque, L., Mukherjee, S., Cao, J.-L., Spencer, S., Marvin, M., Falcon, E., Sidor, M. M., Birnbaum, S. G., Graham, A., Neve, R. L., et al. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.33 · Cited by 120 · see citing works
Psychiatric disorders and mitochondrial dysfunctions.
Marazziti, D., Baroni, S., Picchetti, M., Landi, P., Silvestri, S., Vatteroni, E., & Dell’Osso, M. C. (2012) · PubMed · Cited by 83 · see citing works
Andreazza, A. C., & Young, L. T. (2013) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713000096 · Cited by 80 · see citing works
Bezchlibnyk, Y. B., & Young, L. T. (2002) · The Canadian Journal of Psychiatry · doi:10.1177/070674370204700203 · Cited by 75 · see citing works
Wang, H.-Y., & Friedman, E. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01147-7 · Cited by 53 · see citing works
Imaging Action Potentials with Calcium IndicatorsPreprint
Yuste, R., MacLean, J. N., Vogelstein, J. T., & Paninski, L. (2011) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot5650 · Cited by 48 · see citing works
Bipolar disorder: involvement of signaling cascades and AMPA receptor trafficking at synapses
Du, J., Quiroz, J. A., Yuan, P., Zarate, C. A., & Manji, H. K. (2004) · Neuron Glia Biology · doi:10.1017/s1740925x05000098 · Cited by 43 · see citing works
Chang, A. (2003) · Molecular Brain Research · doi:10.1016/s0169-328x(03)00211-0 · Cited by 37 · see citing works
Kobayashi, M., Sasabe, T., Shiohama, Y., & Koshikawa, N. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.10.047 · Cited by 21 · see citing works
Treatment Use and Costs Among Privately Insured Youths With Diagnoses of Bipolar Disorder
Dusetzina, S. B., Farley, J. F., Weinberger, M., Gaynes, B. N., Sleath, B. L., & Hansen, R. A. (2012) · Psychiatric Services · doi:10.1176/appi.ps.201100516 · Cited by 17 · see citing works
Szulczyk, B., Książek, A., Ladno, W., & Szulczyk, P. J. (2012) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2012-1907 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., Beaulieu, S., et al. (2018) · Bipolar Disorders · doi:10.1111/bdi.12609 · Cited by 1,852 · see citing works
Self-citationGenome-wide association study identifies 30 loci associated with bipolar disorder
eQTLGen Consortium, Stahl, E. A., BIOS Consortium, the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Breen, G., Forstner, A. J., McQuillin, A., Ripke, S., Trubetskoy, V., Mattheisen, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0397-8 · Cited by 1,519 · see citing works
Induced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525 · see citing works
Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior
Gonçalves, J. T., Schafer, S. T., & Gage, F. H. (2016) · Cell · doi:10.1016/j.cell.2016.10.021 · Cited by 1,122 · see citing works
Self-citationVieta, E., Berk, M., Schulze, T. G., Carvalho, A. F., Suppes, T., Calabrese, J. R., Gao, K., Miskowiak, K. W., & Grande, I. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.8 · Cited by 891 · see citing works
Self-citationThe use of brain organoids to investigate neural development and disease
Di Lullo, E., & Kriegstein, A. R. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.107 · Cited by 788 · see citing works
The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease
Berridge, M. J. (2016) · Physiological Reviews · doi:10.1152/physrev.00006.2016 · Cited by 757 · see citing works
Volpato, V., & Webber, C. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.042317 · Cited by 379 · see citing works
DOLPHIN, A. C. (2016) · The Journal of Physiology · doi:10.1113/jp272262 · Cited by 347 · see citing works
Therapeutic targeting of 3′,5′-cyclic nucleotide phosphodiesterases: inhibition and beyond
Baillie, G. S., Tejeda, G. S., & Kelly, M. P. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0033-4 · Cited by 348 · see citing works
Building Models of Brain Disorders with Three-Dimensional Organoids
Amin, N. D., & Paşca, S. P. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.007 · Cited by 312 · see citing works
Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience
Mertens, J., Marchetto, M. C., Bardy, C., & Gage, F. H. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.46 · Cited by 301 · see citing works
Self-citationThe promises and challenges of human brain organoids as models of neuropsychiatric disease
Quadrato, G., Brown, J., & Arlotta, P. (2016) · Nature Medicine · doi:10.1038/nm.4214 · Cited by 304 · see citing works
Advanced Photoacoustic Imaging Applications of Near‐Infrared Absorbing Organic Nanoparticles
Jiang, Y., & Pu, K. (2017) · Small · doi:10.1002/smll.201700710 · Cited by 277 · see citing works
The genetics of bipolar disorder
Gordovez, F. J. A., & McMahon, F. J. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0634-7 · Cited by 268 · see citing works
Wang, P., Mokhtari, R., Pedrosa, E., Kirschenbaum, M. A., Bayrak, C., Zheng, D., & Lachman, H. M. (2017) · Molecular Autism · doi:10.1186/s13229-017-0124-1 · Cited by 255 · see citing works
Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients
Mertens, J., Herdy, J. R., Traxler, L., Schafer, S. T., Schlachetzki, J. C. M., Böhnke, L., Reid, D. A., Lee, H., Zangwill, D., Fernandes, D. P., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.04.004 · Cited by 240 · see citing works
Self-citationThe Emerging Neurobiology of Bipolar Disorder
Harrison, P. J., Geddes, J. R., & Tunbridge, E. M. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.10.006 · Cited by 235 · see citing works
Mitochondria, Metabolism, and Redox Mechanisms in Psychiatric Disorders
Kim, Y., Vadodaria, K. C., Lenkei, Z., Kato, T., Gage, F. H., Marchetto, M. C., & Santos, R. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2018.7606 · Cited by 189 · see citing works
Self-citationTargeting Homeostatic Synaptic Plasticity for Treatment of Mood Disorders
Kavalali, E. T., & Monteggia, L. M. (2020) · Neuron · doi:10.1016/j.neuron.2020.05.015 · Cited by 179 · see citing works
Scaini, G., Mason, B. L., Díaz, A. P., Jha, M. K., Soares, J. C., Trivedi, M. H., & Quevedo, J. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01312-w · Cited by 183 · see citing works
Song, M., Yang, X., Ren, X., Maliskova, L., Li, B., Jones, I. R., Wang, C., Jacob, F., Wu, K. K.-Y., Traglia, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0472-1 · Cited by 167 · see citing works
Self-citationStern, S., Santos, R., Marchetto, M. C., Mendes, A. P. D., Rouleau, G. A., Biesmans, S., Wang, Q.-W., Yao, J., Charnay, P., Bang, A. G., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.260 · Cited by 163 · see citing works
Self-citationHuman induced pluripotent stem cells for modelling neurodevelopmental disorders
Ardhanareeswaran, K., Mariani, J., Coppola, G., Abyzov, A. S., & Vaccarino, F. M. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.45 · Cited by 160 · see citing works
Hoffman, G. E., Hartley, B. J., Flaherty, E. K., Ladran, I., Gochman, P., Ruderfer, D. M., Stahl, E. A., Rapoport, J. L., Sklar, P. B., & Brennand, K. (2017) · Nature Communications · doi:10.1038/s41467-017-02330-5 · Cited by 158 · see citing works
Self-citationPatient-derived induced pluripotent stem cells in cancer research and precision oncology
Papapetrou, E. P. (2016) · Nature Medicine · doi:10.1038/nm.4238 · Cited by 159 · see citing works
Duffy, A. C., Goodday, S., Keown‐Stoneman, C. D. G., & Grof, P. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.18040461 · Cited by 159 · see citing works
A psychiatric disease-related circular RNA controls synaptic gene expression and cognition
Zimmerman, A. J., Hafez, A. K., Amoah, S. K., Rodriguez, B. A., Dell’Orco, M., Lozano, E., Hartley, B. J., Alural, B., Lalonde, J., Chander, P. N., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0653-4 · Cited by 152 · see citing works
Self-citationThe role of mitochondria in mood disorders: from physiology to pathophysiology and to treatment
Giménez-Palomo, A., Dodd, S., Anmella, G., Carvalho, A. F., Scaini, G., Quevedo, J., Pacchiarotti, I., Vieta, E., & Berk, M. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.546801 · Cited by 140 · see citing works
Amare, A. T., Schubert, K. O., Hou, L., Clark, S. R., Papiol, S., Heilbronner, U., Degenhardt, F., Ayele, F. T., Hsu, Y., Shekhtman, T., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.3433 · Cited by 157 · see citing works
Self-citationComplex Tissue and Disease Modeling using hiPSCs
Passier, R., Orlova, V., & Mummery, C. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.02.011 · Cited by 142 · see citing works
Santos, R., Vadodaria, K. C., Jaeger, B. N., Mei, A., Lefcochilos-Fogelquist, S., Mendes, A. P. D., Erikson, G. A., Shokhirev, M. N., Randolph‐Moore, L., Fredlender, C., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.05.011 · Cited by 138 · see citing works
Self-citationTobe, B. T. D., Crain, A., Winquist, A., Calabrese, B., Makihara, H., Zhao, W., Lalonde, J., Nakamura, H., Konopaske, G. T., Sidor, M. M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700111114 · Cited by 138 · see citing works
Self-citationInflammatory signaling mechanisms in bipolar disorder
Jones, G. H., Vecera, C. M., Pinjari, O. F., & Machado‐Vieira, R. (2021) · Journal of Biomedical Science · doi:10.1186/s12929-021-00742-6 · Cited by 141 · see citing works
Kato, T. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12852 · Cited by 138 · see citing works
Therapeutic Mechanisms of Lithium in Bipolar Disorder: Recent Advances and Current Understanding
Malhi, G. S., & Outhred, T. (2016) · CNS Drugs · doi:10.1007/s40263-016-0380-1 · Cited by 133 · see citing works
Pluripotent stem cells in neuropsychiatric disorders
Soliman, M. A., Aboharb, F., Zeltner, N., & Studer, L. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.40 · Cited by 129 · see citing works
Buchsbaum, I. Y., & Cappello, S. (2019) · Development · doi:10.1242/dev.163766 · Cited by 128 · see citing works
Neurobiological basis of bipolar disorder: Mitochondrial dysfunction hypothesis and beyond
Kato, T. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.10.037 · Cited by 129 · see citing works
Phosphoinositides: Regulators of Nervous System Function in Health and Disease
Raghu, P., Joseph, A., Krishnan, H., Singh, P. K., & Saha, S. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00208 · Cited by 123 · see citing works
Sawada, T., Chater, T. E., Sasagawa, Y., Yoshimura, M., Fujimori-Tonou, N., Tanaka, K. Y., Benjamin, K. J., Paquola, A. C. M., Erwin, J. A., Goda, Y., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0844-z · Cited by 121 · see citing works
Advancing models of neural development with biomaterials
Roth, J. G., Huang, M. S., Li, T. L., Feig, V. R., Jiang, Y., Cui, B., Greely, H. T., Bao, Z., Pașca, S. P., & Heilshorn, S. C. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00496-y · Cited by 120 · see citing works
Molecular Mechanisms of Bipolar Disorder: Progress Made and Future Challenges
Kim, Y., Santos, R., Gage, F. H., & Marchetto, M. C. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00030 · Cited by 120 · see citing works
Self-citationLogan, S., Arzua, T., Canfield, S. G., Seminary, E. R., Sison, S. L., Ebert, A. D., & Bai, X. (2019) · Comprehensive physiology · doi:10.1002/cphy.c180025 · Cited by 139 · see citing works
Roles of mitochondria in neuronal development
Son, G., & Han, J. (2018) · BMB Reports · doi:10.5483/bmbrep.2018.51.11.226 · Cited by 117 · see citing works
Innovative approaches to bipolar disorder and its treatment
Harrison, P. J., Cipriani, A., Harmer, C. J., Nobre, A. C., Saunders, K. E. A., Goodwin, G. M., & Geddes, J. R. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13048 · Cited by 114 · see citing works
A Single-Cell Model for Synaptic Transmission and Plasticity in Human iPSC-Derived Neurons
Meijer, M., Rehbach, K., Brunner, J., Classen, J., Lammertse, H. C. A., van Linge, L. A., Schut, D., Krutenko, T., Hebisch, M., Cornelisse, L. N., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.058 · Cited by 111 · see citing works
Cipriani, A., Saunders, K. E. A., Attenburrow, M.-J., Stefaniak, J. D., Panchal, P., Stockton, S., Lane, T. A., Tunbridge, E. M., Geddes, J. R., & Harrison, P. J. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.86 · Cited by 111 · see citing works
Neurodevelopmental origins of bipolar disorder: iPSC models
O’Shea, K. S., & McInnis, M. G. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.11.006 · Cited by 107 · see citing works
Jaffe, A. E., Hoeppner, D. J., Saito, T., Blanpain, L. T., Ukaigwe, J., Burke, E. E., Collado‐Torres, L., Tao, R., Tajinda, K., Maynard, K. R., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0604-z · Cited by 95 · see citing works
Cellular calcium in bipolar disorder: systematic review and meta-analysis
Harrison, P. J., Hall, N., Mould, A. W., Al‐Juffali, N., & Tunbridge, E. M. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0622-y · Cited by 96 · see citing works
Altered serotonergic circuitry in SSRI-resistant major depressive disorder patient-derived neurons
Vadodaria, K. C., Ji, Y., Skime, M. K., Paquola, A. C. M., Nelson, T. J., Hall‐Flavin, D. K., Heard, K. J., Fredlender, C., Deng, Y., Elkins, J., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0377-5 · Cited by 95 · see citing works
Self-citationInduced pluripotent stem cells for neural drug discovery
Farkhondeh, A., Li, R., Gorshkov, K., Chen, K. G., Might, M., Rodems, S. M., Lo, D. C., & Zheng, W. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.01.007 · Cited by 90 · see citing works
Prediction of lithium response using clinical data
Nunes, A., Ardau, R., Berghöfer, A., Bocchetta, A., Chillotti, C., Deiana, V., Garnham, J. S., Grof, E., Hájek, T., Manchia, M., et al. (2019) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.13122 · Cited by 89 · see citing works
Self-citationRoss, C. A., & Margolis, R. L. (2019) · Complex Psychiatry · doi:10.1159/000501797 · Cited by 84 · see citing works
Goes, F. S. (2016) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2015.10.004 · Cited by 85 · see citing works
Modeling psychiatric disorders: from genomic findings to cellular phenotypes
Falk, A., Heine, V. M., Harwood, A. J., Sullivan, P. F., Peitz, M., Brüstle, O., Shen, S., Sun, Y.-M., Glover, J. C., Posthuma, D., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.89 · Cited by 86 · see citing works
Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons
Vadodaria, K. C., Ji, Y., Skime, M. K., Paquola, A. C. M., Nelson, T. J., Hall‐Flavin, D. K., Fredlender, C., Heard, K. J., Deng, Y., Le, A. T., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0363-y · Cited by 85 · see citing works
Self-citationModeling psychiatric disorders with patient-derived iPSCs
Wen, Z., Christian, K. M., Song, H., & Ming, G.-L. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.11.003 · Cited by 84 · see citing works
Puglisi‐Allegra, S., Ruggieri, S. A., & Fornai, F. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01492-7 · Cited by 84 · see citing works
Human pluripotent stem cell–derived models and drug screening in CNS precision medicine
Silva, M. C., & Haggarty, S. J. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14012 · Cited by 82 · see citing works
Haukvik, U. K., Gurholt, T. P., Nerland, S., Elvsåshagen, T., Akudjedu, T. N., Alda, M., Alnæs, D., Alonso-Lana, S., Bauer, J., Baune, B. T., et al. (2020) · Human Brain Mapping · doi:10.1002/hbm.25249 · Cited by 82 · see citing works
Self-citationKovács, Z., D’Agostino, D. P., Diamond, D. M., Kindy, M. S., Rogers, C. Q., & Ari, C. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00363 · Cited by 84 · see citing works
Chang, C.-W., Evans, M. D., Yu, X., Yu, G.-Q., & Mucke, L. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109855 · Cited by 81 · see citing works
iPlasticity: Induced juvenile‐like plasticity in the adult brain as a mechanism of antidepressants
Umemori, J., Winkel, F., Didio, G., Llach Pou, M., & Castrén, E. (2018) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12683 · Cited by 80 · see citing works
Advances toward precision medicine for bipolar disorder: mechanisms & molecules
Haggarty, S. J., Karmacharya, R., & Perlis, R. H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0831-4 · Cited by 77 · see citing works
Mitochondrial dysfunction as a critical event in the pathophysiology of bipolar disorder
Scaini, G., Andrews, T., Lima, C. N. D. C., Benevenuto, D., STRECK, E. L., & Quevedo, J. (2020) · Mitochondrion · doi:10.1016/j.mito.2020.12.002 · Cited by 77 · see citing works
High-Throughput and Cost-Effective Characterization of Induced Pluripotent Stem Cells
D’Antonio, M., Woodruff, G., Nathanson, J. L., D’Antonio‐Chronowska, A., Arias, A. D., Matsui, H., Williams, R. M., Herrera, C. M., Reyna, S. M., Yeo, G. W.-M., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.03.011 · Cited by 76 · see citing works
Modeling neuropsychiatric disorders using human induced pluripotent stem cells
Wang, M., Zhang, L., & Gage, F. H. (2019) · Protein & Cell · doi:10.1007/s13238-019-0638-8 · Cited by 75 · see citing works
Self-citationAdvances in development and application of human organoids
Shankaran, A., Prasad, K., Chaudhari, S., Brand, A. M., & Satyamoorthy, K. (2021) · 3 Biotech · doi:10.1007/s13205-021-02815-7 · Cited by 74 · see citing works
Wang, M., Zhang, L., Novak, S. W., Yu, J., Gallina, I. S., Xu, L. L., Lim, C. K., Fernandes, S., Shokhirev, M. N., Williams, A. E., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02157-8 · Cited by 74 · see citing works
Self-citationSantos, R., Linker, S. B., Stern, S., Mendes, A. P. D., Shokhirev, M. N., Erikson, G. A., Randolph‐Moore, L., Racha, V., Kim, Y., Kelsoe, J. R., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00981-3 · Cited by 65 · see citing works
Self-citationNew considerations for hiPSC-based models of neuropsychiatric disorders
Hoffman, G. E., Schrode, N., Flaherty, E. K., & Brennand, K. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0029-1 · Cited by 65 · see citing works
Self-citationPrediction of response to drug therapy in psychiatric disorders
Stern, S., Linker, S. B., Vadodaria, K. C., Marchetto, M. C., & Gage, F. H. (2018) · Open Biology · doi:10.1098/rsob.180031 · Cited by 65 · see citing works
Self-citationSeah, C., Breen, M. S., Rusielewicz, T., Bader, H. N., Xu, C., Hunter, C. J., McCarthy, B., Deans, P. J. M., Chattopadhyay, M., Goldberg, J., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01161-y · Cited by 67 · see citing works
Self-citationBipolar disorder: definition, differential diagnosis, clinical contexts and therapeutic approaches
Perrotta, G. (2019) · Neuroscience and Neurological Surgery · doi:10.31579/2578-8868/097 · Cited by 64 · see citing works
Mitochondrial Dysfunction in Schizophrenia
Ni, P., & Chung, S. (2020) · BioEssays · doi:10.1002/bies.201900202 · Cited by 63 · see citing works
New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview
Bortolozzi, A. A., Fico, G., Berk, M., Solmi, M., Fornaro, M., Quevedo, J., Zarate, C. A., Kessing, L. V., Vieta, E., & Carvalho, A. F. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000007 · Cited by 61 · see citing works
Geoffroy, P. A., Étain, B., Lajnef, M., Zerdazi, E., Brichant‐Petitjean, C., Heilbronner, U., Hou, L., Degenhardt, F. C., Rietschel, M., McMahon, F. J., et al. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12306 · Cited by 61 · see citing works
Depressive patient‐derived GABA interneurons reveal abnormal neural activity associated with HTR2C
Lu, K., Hong, Y., Tao, M., Shen, L., Zheng, Z., Fang, K.-H., Yuan, F., Xu, M., Wang, C., Zhu, D., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202216364 · Cited by 59 · see citing works
Stern, S., Sarkar, A., Stern, T., Mei, A., Mendes, A. P. D., Stern, Y., Goldberg, G., Galor, D., Nguyen, T., Randolph-Moore, L., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.09.018 · Cited by 59 · see citing works
Self-citationLi, M., Jiang, Z.-E., Ling-yun, S., Quan, Z., & Yu, H.-L. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2016.12.072 · Cited by 59 · see citing works
Lee, Y., Zhang, Y., Kim, S., & Han, K. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0028-y · Cited by 59 · see citing works
Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscaling
Gideons, E. S., Lin, P.-Y., Mahgoub, M., Kavalali, E. T., & Monteggia, L. M. (2017) · eLife · doi:10.7554/elife.25480 · Cited by 57 · see citing works
Licinio, J., & Wong, M. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.201 · Cited by 57 · see citing works
Metabolism navigates neural cell fate in development, aging and neurodegeneration
Traxler, L., Lagerwall, J., Eichhorner, S., Stefanoni, D., D’Alessandro, A., & Mertens, J. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.048993 · Cited by 57 · see citing works
Self-citationAdvancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models
Haggarty, S. J., Silva, M. C., Cross, A. J., Brandon, N. J., & Perlis, R. H. (2016) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2016.01.011 · Cited by 56 · see citing works
Next‐generation disease modeling with direct conversion: a new path to old neurons
Traxler, L., Edenhofer, F., & Mertens, J. (2019) · FEBS Letters · doi:10.1002/1873-3468.13678 · Cited by 55 · see citing works
Self-citationMcGhee, C. E., Yang, Z., Guo, W., Wu, Y., Lyu, M., DeLong, C. J., Hong, S., Ma, Y., McInnis, M. G., O’Shea, K. S., et al. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00843 · Cited by 55 · see citing works
Mitochondrial dysfunction in psychiatric disorders
Ni, P., Ma, Y., & Chung, S. (2022) · Schizophrenia Research · doi:10.1016/j.schres.2022.08.027 · Cited by 55 · see citing works
Emerging metallenes: synthesis strategies, biological effects and biomedical applications
Lu, C., Li, R., Miao, Z., Wang, F., & Zha, Z. (2023) · Chemical Society Reviews · doi:10.1039/d2cs00586g · Cited by 55 · see citing works
Osete, J. R., Akkouh, I. A., de Assis, D. R., Szabó, A., Frei, E., Hughes, T., Smeland, O. B., Steen, N. E., Andreassen, O. A., & Djurovic, S. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01164-4 · Cited by 56 · see citing works
Liu, Y., Xiao, X., Yang, Y., Yao, R., Yang, Q., Zhu, Y., Yang, X., Zhang, S., Shen, L. H., & Jiao, B. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14049 · Cited by 54 · see citing works
Drouin‐Ouellet, J., Pircs, K., Barker, R. A., Jakobsson, J., & Parmar, M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00530 · Cited by 54 · see citing works
Modeling Brain Disorders Using Induced Pluripotent Stem CellsPreprint
Vadodaria, K. C., Jones, J. R., Linker, S. B., & Gage, F. H. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035659 · Cited by 51 · see citing works
Self-citationDas, S. C., Hjelm, B., Rollins, B., Sequeira, A., Morgan, L. Z., Omidsalar, A. A., Schatzberg, A., Barchas, J., Lee, F., Myers, R., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02127-1 · Cited by 45 · see citing works
What Should a Psychiatrist Know About Genetics?
Nürnberger, J. I., Austin, J., Berrettini, W. H., Besterman, A. D., DeLisi, L. E., Grice, D. E., Kennedy, J. L., Moreno‐De‐Luca, D., Potash, J. B., Ross, D. A., et al. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.17nr12046 · Cited by 52 · see citing works
Geerts, H., Wikswo, J. P., van der Graaf, P. H., Bai, J. P. F., Gaiteri, C., Bennett, D. A., Swalley, S. E., Schuck, E. L., Kaddurah‐Daouk, R., Tsaioun, K., et al. (2019) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12478 · Cited by 49 · see citing works
Fiksinski, A., Hoftman, G. D., Vorstman, J. A. S., & Bearden, C. E. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01783-5 · Cited by 52 · see citing works
Ren, W., Fu, C.-L., Zhang, Y., Ju, X., Jiang, X., Song, J., Gong, M., Li, Z., Fan, W., Yao, J., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2403235121 · Cited by 50 · see citing works
Self-citation
- Authors
- Study, T. P. O. B. D., Mertens, J., Wang, Q.-W., Kim, Y., Yu, D. X., Pham, S., Yang, B., Zheng, Y., Diffenderfer, K. E., Zhang, J., Soltani, S., Eames, T., Schafer, S. T., Boyer, L., Marchetto, M. C., Nurnberger, J. I., Calabrese, J. R., Oedegaard, K. J., McCarthy, M. J., Zandi, P. P., Alda, M., Nievergelt, C. M., Mi, S., Brennand, K. J., Kelsoe, J. R., Gage, F. H., & Yao, J.
- Affiliations
- Center for Life Sciences (CN)
- Salk Institute for Biological Studies (US)
- Chinese Academy of Sciences (CN)
- Case Western Reserve University (US)
- Haukeland University Hospital (NO)
- University of California San Diego (US)
- Johns Hopkins University (US)
- Dalhousie University (CA)
- Icahn School of Medicine at Mount Sinai (US)
- Jiangsu Normal University (CN)
- Corresponding author
- Kelsoe, John R.
- Gage, Fred H.
- Yao, Jun
- ORCID
- Venue
- Nature
- Published
- 2015-10-28
- Volume
- 527
- Issue
- 7576
- Pages
- 95-99
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4742055
- OpenAlex
- W2139372806
- Cited by
- 562
- References
- 30
- Citations by year
- 2026: 20 · 2025: 50 · 2024: 45 · 2023: 37 · 2022: 54 · 2021: 60 · 2020: 58 · 2019: 68 · 2018: 50 · 2017: 54 · 2016: 58 · 2015: 5 · 2014: 2
- FWCI
- 45.23
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-11-25)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- PMC
- Funders
- U.S. Department of Veterans Affairs (I01CX000363)
- National Institute of Mental Health (R01MH106056, U01 MH92758, R01MH101454, MH106056, U01MH092758)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- bipolar disorder, lithium response, lithium resistance, neuronal hyperexcitability, iPSC-derived neurons, mitochondrial abnormalities, action potential firing, endophenotypes, iPSC disease models, mood stabilizers, calcium imaging, patch-clamp electrophysiology, drug response prediction, personalized medicine, mania
- MeSH terms
- Action Potentials, Bipolar Disorder, Humans, Male, Mitochondria, Neurons, Antipsychotic Agents, Lithium Compounds, Patch-Clamp Techniques, Dentate Gyrus, Calcium Signaling, Induced Pluripotent Stem Cells, Endophenotypes
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