DISC1 and PDE4B Are Interacting Genetic Factors in Schizophrenia That Regulate cAMP Signaling
Abstract
The disrupted in schizophrenia 1 ( DISC1 ) gene is a candidate susceptibility factor for schizophrenia, but its mechanistic role in the disorder is unknown. Here we report that the gene encoding phosphodiesterase 4B ( PDE4B ) is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness. The PDEs inactivate adenosine 3′,5′-monophosphate (cAMP), a second messenger implicated in learning, memory, and mood. We show that DISC1 interacts with the UCR2 domain of PDE4B and that elevation of cellular cAMP leads to dissociation of PDE4B from DISC1 and an increase in PDE4B activity. We propose a mechanistic model whereby DISC1 sequesters PDE4B in resting cells and releases it in an activated state in response to elevated cAMP.
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DISC1 normally provides negative feedback on cAMP signalling, but a mutation in DISC1 decreased the activity of the phosphodiesterase PDE4B in the presence of high concentrations of cAMP.
“For example, disrupted in schizophrenia 1 (DISC1) normally provides negative feedback on cAMP signalling, but a mutation in DISC1 decreased the activity of the phosphodiesterase PDE4B in the presence of high concentrations of cAMP128.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [128]
DISC1 anchors the phosphodiesterases (PDE4s) that catabolize cAMP and regulate its signaling.
“Particularly relevant to stress signaling in PFC, DISC1 anchors the phosphodiesterases (PDE4s) that catabolize cAMP and regulate its signaling121,125.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [121]
DISC1 is critical for regulation of the stress response in PFC.
“Emerging data indicate that the scaffolding protein Disrupted In Schizophrenia 1 (DISC1) is critical for regulation of the stress response in PFC, suggesting that genetic insults that interfere with the function of this protein increase the risk for stress-related psychiatric disorders.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [121]
Mutations in DISC1 are associated with high rates of mental illness.
“Mutations in DISC1 are associated with high rates of mental illness120,121, and more subtle polymorphisms are associated with decreased PFC gray matter and impaired working memory122,123.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [121]
Cites
Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence
Harrison, P. J., & Weinberger, D. R. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001558 · Cited by 2,020 · see citing works
Disruption of two novel genes by a translocation co-segregating with schizophrenia
Millar, J. K. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.9.1415 · Cited by 1,254 · see citing works
Self-citationHouslay, M. D., & Adams, D. R. (2003) · Biochemical Journal · doi:10.1042/bj20021698 · Cited by 764 · see citing works
Self-citationBlackwood, D., Fordyce, A., Walker, M. T., Clair, D. M. S., Porteous, D. J., & Muir, W. J. (2001) · The American Journal of Human Genetics · doi:10.1086/321969 · Cited by 734 · see citing works
Self-citationSette, C., & Conti, M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.28.16526 · Cited by 412 · see citing works
Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth
Miyoshi, K., Honda, A., Baba, K., Taniguchi, M., Oono, K., Fujita, T., Kuroda, S., Katayama, T., & Tohyama, M. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001352 · Cited by 314 · see citing works
Antidepressant effects of inhibitors of cAMP phosphodiesterase (PDE4)
O’Donnell, J. M., & Zhang, H. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.01.003 · Cited by 307 · see citing works
MacKenzie, S. J., Baillie, G. S., McPhee, I., MacKenzie, C., SEAMONS, R. A., McSorley, T., Millen, J. E., Beard, M., Heeke, G. V., & Houslay, M. D. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704743 · Cited by 261 · see citing works
Self-citationZhang, H. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(02)00344-5 · Cited by 228 · see citing works
Brandon, N. J., Handford, E. J., Schurov, I., Rain, J., Pelling, M., Duran-Jimenez, B., Camargo, L. M., Oliver, K. R., Beher, D., Shearman, M. S., et al. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2003.09.009 · Cited by 224 · see citing works
Self-citationJames, R., Adams, R. R., CHRISTIE, S., Buchanan, S. R., Porteous, D. J., & Millar, J. K. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.01.013 · Cited by 150 · see citing works
Self-citationThe cyclic AMP system andDrosophila learning
Davis, R. L., Cherry, J., Dauwalder, B., Han, P., & Skoulakis, E. M. C. (1995) · Molecular and Cellular Biochemistry · doi:10.1007/bf01076588 · Cited by 130 · see citing works
Beard, M., Olsen, A. E., Jones, R. E., Erdoğan, S., Houslay, M. D., & Bolger, G. B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10349 · Cited by 129 · see citing works
Self-citationMcCahill, A., McSorley, T., Huston, E., HILL, E., Lynch, M. J., Gall, I., Keryer, G., Lygren, B., Taskén, K., & Vanheeke, G. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.04.003 · Cited by 115 · see citing works
Self-citationCloning and characterization of Disc1, the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1).
Ma, L., Liu, Y., Ky, B., Shughrue, P., Austin, C., & Morris, J. A. (2002) · Genomics · doi:10.1006/geno.2002.7012 · Cited by 98 · see citing works
Lamprecht, R. (1999) · Cellular and Molecular Life Sciences · doi:10.1007/s000180050314 · Cited by 97 · see citing works
DISC1 (Disrupted in Schizophrenia-1) is expressed in limbic regions of the primate brain
Austin, C. P., Ma, L., Ky, B., Morris, J. A., & Shughrue, P. J. (2003) · Neuroreport · doi:10.1097/01.wnr.0000074342.81633.63 · Cited by 76 · see citing works
Hayashi, M. A. F., Portaro, F. C. V., Bastos, M. F., Guerreiro, J. R., Oliveira, V., Gorrão, S. S., Tambourgi, D. V., Sant’Anna, O. A., Whiting, P. J., Camargo, L. M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500330102 · Cited by 75 · see citing works
Self-citationOrchestration of synaptic plasticity through AKAP signaling complexes
Bauman, A. L., Goehring, A. S., & Scott, J. D. (2003) · Neuropharmacology · doi:10.1016/j.neuropharm.2003.09.016 · Cited by 61 · see citing works
Thomson, P. A., Wray, N. R., Millar, J. K., Evans, K. L., Hellard, S. L., Condie, A., Muir, W. J., Blackwood, D., & Porteous, D. J. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001699 · Cited by 22 · see citing works
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Global variation in copy number in the human genome
Redon, R., Ishikawa, S., Fitch, K. R., Feuk, L., Perry, G. H., Andrews, T. D., Fiegler, H., Shapero, M. H., Carson, A. R., Chen, W., et al. (2006) · Nature · doi:10.1038/nature05329 · Cited by 4,276 · see citing works
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299 · see citing works
Cyclic Nucleotide Phosphodiesterases: Molecular Regulation to Clinical Use
Bender, A. T., & Beavo, J. A. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.5 · Cited by 1,787 · see citing works
GERAD1 Consortium, Pardiñas, A. F., CRESTAR Consortium, Holmans, P., Pocklington, A. J., Escott-Price, V., Ripke, S., Carrera, N., Legge, S. E., Bishop, S., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0059-2 · Cited by 1,552 · see citing works
Self-citationConti, M., & Beavo, J. A. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060305.150444 · Cited by 1,188 · see citing works
The Neuropsychopharmacology of Fronto-Executive Function: Monoaminergic Modulation
Robbins, T. W., & Arnsten, A. F. T. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135535 · Cited by 957 · see citing works
Overview of PDEs and Their Regulation
Omori, K., & Kotera, J. (2007) · Circulation Research · doi:10.1161/01.res.0000256354.95791.f1 · Cited by 797 · see citing works
Advances in targeting cyclic nucleotide phosphodiesterases
Maurice, D. H., Ke, H., Ahmad, F., Wang, Y., Chung, J. H., & Manganiello, V. C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4228 · Cited by 789 · see citing works
Stress weakens prefrontal networks: molecular insults to higher cognition
Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752 · see citing works
Ross, C. A., Margolis, R. L., Reading, S. A. J., Pletnikov, M. V., & Coyle, J. T. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.015 · Cited by 697 · see citing works
Wang, M., Ramos, B. P., Paspalas, C. D., Shu, Y., Simen, A., Duque, A., Vijayraghavan, S., Brennan, A., Dudley, A., Nou, E., et al. (2007) · Cell · doi:10.1016/j.cell.2007.03.015 · Cited by 672 · see citing works
Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions
Francis, S. H., Blount, M. A., & Corbin, J. D. (2011) · Physiological Reviews · doi:10.1152/physrev.00030.2010 · Cited by 644 · see citing works
The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia
Howes, O. D., McCutcheon, R. A., Owen, M. J., & Murray, R. M. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.07.014 · Cited by 604 · see citing works
Gao, R., & Penzes, P. (2015) · Current Molecular Medicine · doi:10.2174/1566524015666150303003028 · Cited by 516 · see citing works
Arnsten, A. F. T., Wang, M. J., & Paspalas, C. D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.038 · Cited by 538 · see citing works
Behavioral phenotypes of Disc1 missense mutations in mice
Clapcote, S. J., Lipina, T. V., Millar, J. K., Mackie, S., Christie, S., Ogawa, F., Lerch, J. P., Trimble, K., Uchiyama, M., Sakuraba, Y., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.04.015 · Cited by 526 · see citing works
Self-citationPsychiatric genetics: progress amid controversy
Burmeister, M., McInnis, M. G., & Zöllner, S. K. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2381 · Cited by 522 · see citing works
The DISC locus in psychiatric illness
Chubb, J. E., Bradshaw, N. J., Soares, D. C., Porteous, D. J., & Millar, J. K. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002106 · Cited by 542 · see citing works
Self-citationUnderpinning compartmentalised cAMP signalling through targeted cAMP breakdown
Houslay, M. D. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.09.007 · Cited by 431 · see citing works
Self-citationLinking neurodevelopmental and synaptic theories of mental illness through DISC1
Brandon, N. J., & Sawa, A. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn3120 · Cited by 422 · see citing works
Self-citationHikida, T., Jaaro-Peled, H., Seshadri, S., Oishi, K., Hookway, C., Kong, S., Wu, D., Xue, R., Andradé, M., Tankou, S. K., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704774104 · Cited by 417 · see citing works
Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1
Hayashi-Takagi, A., Takaki, M., Graziane, N., Seshadri, S., Murdoch, H., Dunlop, A. J., Makino, Y., Seshadri, A. J., Ishizuka, K., Srivastava, D. P., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2487 · Cited by 399 · see citing works
Self-citationCamargo, L. M., Collura, V, Rain, J.-C., Mizuguchi, K., Hermjakob, H., Kerrien, S., Bonnert, T. P., Whiting, P. J., & Brandon, N. J. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001880 · Cited by 405 · see citing works
Self-citationBurgin, A. B., Magnússon, Ó. Þ., Singh, J., Witte, P., Staker, B. L., Björnsson, J. M., Þorsteinsdóttir, M., Hrafnsdóttir, S., Hagen, T. J., Kiselyov, A. S., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1598 · Cited by 396 · see citing works
Phosphodiesterases in the CNS: targets for drug development
Menniti, F. S., Faraci, W. S., & Schmidt, C. J. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2058 · Cited by 391 · see citing works
Horvath, A., Boikos, S., Giatzakis, C., Robinson-White, A., Groussin, L., Griffin, K. J., Stein, E., Levine, E., Delimpasi, G., Hsiao, H. P., et al. (2006) · Nature Genetics · doi:10.1038/ng1809 · Cited by 352 · see citing works
Pletnikov, M. V., Ayhan, Y., Nikolskaia, O. V., Xu, Y., Ovanesov, M. V., Huang, H., Mori, S., Moran, T. H., & Ross, C. A. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002079 · Cited by 339 · see citing works
Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia
Vacic, V., McCarthy, S., Malhotra, D., Murray, F., Chou, H.-H., Peoples, A., Makarov, V., Yoon, S., Bhandari, A., Corominas, R., et al. (2011) · Nature · doi:10.1038/nature09884 · Cited by 337 · see citing works
Clinical and Molecular Genetics of the Phosphodiesterases (PDEs)
Azevedo, M. F., Faucz, F. R., Bimpaki, E. I., Horvath, A., Levy, I., de Alexandre, R. B., Ahmad, F., Manganiello, V. C., & Stratakis, C. A. (2013) · Endocrine Reviews · doi:10.1210/er.2013-1053 · Cited by 326 · see citing works
Pathophysiologically based treatment interventions in schizophrenia
Lewis, D. A., & González‐Burgos, G. (2006) · Nature Medicine · doi:10.1038/nm1478 · Cited by 320 · see citing works
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Raker, V., Becker, C., & Steinbrink, K. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00123 · Cited by 321 · see citing works
Jaaro-Peled, H., Hayashi‐Takagi, A., Seshadri, S., Kamiya, A., Brandon, N. J., & Sawa, A. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.05.007 · Cited by 315 · see citing works
Self-citationcAMP-Specific Phosphodiesterase-4 Enzymes in the Cardiovascular System
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Lee, J. A., & Lupski, J. R. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.027 · Cited by 289 · see citing works
Nishimura, Y., Martin, C. L., Vazquez-Lopez, A., Spence, S. J., Alvarez-Retuerto, A. I., Sigman, M., Steindler, C., Pellegrini, S., Schanen, N. C., Warren, S. T., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm116 · Cited by 276 · see citing works
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Koike, H., Arguello, P. A., Kvajo, M., Karayiorgou, M., & Gogos, J. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511189103 · Cited by 276 · see citing works
Kvajo, M., McKellar, H., Arguello, P. A., Drew, L. J., Moore, H., MacDermott, A. B., Karayiorgou, M., & Gogos, J. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802615105 · Cited by 268 · see citing works
Sebat, J., Levy, D. L., & McCarthy, S. E. (2009) · Trends in Genetics · doi:10.1016/j.tig.2009.10.004 · Cited by 260 · see citing works
Schizophrenia-Related Neural and Behavioral Phenotypes in Transgenic Mice Expressing TruncatedDisc1
Shen, S., Lang, B., Nakamoto, C., Zhang, F., Pu, J., Kuan, S. L., Chatzi, C. A., He, S., Mackie, I., Brandon, N. J., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3299-08.2008 · Cited by 250 · see citing works
Self-citationHashimoto, R., Numakawa, T., Ohnishi, T., Kumamaru, E., Yagasaki, Y., Ishimoto, T., Mori, T., Nemoto, K., Adachi, N., Izumi, A., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl244 · Cited by 247 · see citing works
Mendelian disorders deserve more attention
Antonarakis, S. E., & Beckmann, J. S. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1826 · Cited by 241 · see citing works
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Snyder, M. A., & Gao, W. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00031 · Cited by 237 · see citing works
Ernst, C., Deleva, V., Deng, X., Sequeira, A., Pomarenski, A., Klempan, T., Ernst, N., Quirion, R., Gratton, A., Szyf, M., et al. (2009) · Archives of General Psychiatry · doi:10.1001/archpsyc.66.1.22 · Cited by 235 · see citing works
Li, Y., Cheng, Y., Huang, Y., Conti, M., Wilson, S. P., O’Donnell, J. M., & Zhang, H. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5236-10.2011 · Cited by 233 · see citing works
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Baillie, G. S. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.06926.x · Cited by 227 · see citing works
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Seshadri, S. S., DeStefano, A. L., Au, R., Massaro, J. M., Beiser, A., Kelly‐Hayes, M., Kase, C. S., D’Agostino, R. B., DeCarli, C. S., Atwood, L. D., et al. (2007) · BMC Medical Genetics · doi:10.1186/1471-2350-8-s1-s15 · Cited by 199 · see citing works
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Kilpinen, H., Ylisaukko‐oja, T., Hennah, W., Palo, O. M., Varilo, T., Vanhala, R., Wendt, T. N., von Wendt, L., Paunio, T., & Peltonen, L. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002031 · Cited by 193 · see citing works
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Bradshaw, N. J., & Porteous, D. J. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.12.027 · Cited by 188 · see citing works
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Nakata, K., Lipska, B. K., Hyde, T. M., Ye, T., Newburn, E. N., Morita, Y., Vakkalanka, R., Barenboim, M., Sei, Y., Weinberger, D. R., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903413106 · Cited by 182 · see citing works
Borovac, J., Bosch, M., & Okamoto, K. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.07.001 · Cited by 180 · see citing works
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Balu, D. T., & Coyle, J. T. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.005 · Cited by 182 · see citing works
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Zhang, H., Huang, Y., Masood, A., Stolinski, L. R., Li, Y., Zhang, L., Dlaboga, D., Jin, S.-L. C., Conti, M., & O’Donnell, J. M. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301537 · Cited by 180 · see citing works
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Self-citationKamiya, A., Tomoda, T., Chang, J., Takaki, M., Zhan, C., Morita, M., Cascio, M. B., Elashvili, S., Koizumi, H., Takanezawa, Y., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl407 · Cited by 171 · see citing works
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Lipska, B. K., Peters, T., Hyde, T. M., Halim, N., Horowitz, C., Mitkus, S., Weickert, C. S., Matsumoto, M., Sawa, A., Straub, R. E., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl040 · Cited by 168 · see citing works
Enomoto, A., Asai, N., Namba, T., Wang, Y., Kato, T., Tanaka, M., Tatsumi, H., Taya, S., Tsuboi, D., Kuroda, K., et al. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.015 · Cited by 167 · see citing works
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Hennah, W., Thomson, P. A., McQuillin, A., Bass, N. J., Loukola, A., Anjorin, A., Blackwood, D., Curtis, D., Deary, I. J., Harris, S. E., et al. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.22 · Cited by 165 · see citing works
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Arnsten, A. F. T., Paspalas, C. D., Gamo, N. J., Yang, Y., & Wang, M. (2010) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2010.05.003 · Cited by 160 · see citing works
Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders
Delhaye, S., & Bardoni, B. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00997-9 · Cited by 155 · see citing works
Rolipram: A specific phosphodiesterase 4 inhibitor with potential antipsychotic activity
Kanes, S., Tokarczyk, J., Siegel, S. J., Bilker, W. B., Abel, T. G., & Kelly, M. P. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.09.026 · Cited by 158 · see citing works
Murdoch, H., Mackie, S., Collins, D. M., Hill, E. V., Bolger, G. B., Klußmann, E., Porteous, D. J., Millar, J. K., & Houslay, M. D. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1493-07.2007 · Cited by 152 · see citing works
Self-citationAyhan, Y., Abazyan, B., Nomura, J., Kim, R., Ladenheim, B., Krasnova, I. N., Sawa, A., Margolis, R. L., Cadet, J. L., Mori, S., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2009.144 · Cited by 148 · see citing works
Mechanisms for the Modulation of Dopamine D1 Receptor Signaling in Striatal Neurons
Nishi, A., Kuroiwa, M., & Shuto, T. (2011) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2011.00043 · Cited by 148 · see citing works
PDE4 as a target for cognition enhancement
Richter, W., Menniti, F. S., Zhang, H., & Conti, M. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.818656 · Cited by 148 · see citing works
Stefan, E., Wiesner, B., Baillie, G. S., Mollajew, R., Henn, V., Lorenz, D., Furkert, J., Santamaria, K., Nedvetsky, P. I., Hundsrucker, C., et al. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006020132 · Cited by 148 · see citing works
Self-citationPark, Y.-U., Jeong, J., Lee, H., Mun, J. Y., Kim, J.-H., Lee, J. S., Nguyen, M. D., Han, S. S., Suh, P.-G., & Park, S. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004361107 · Cited by 143 · see citing works
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Singh, K. K., Ge, X., Mao, Y., Drane, L., Meletis, K., Samuels, B. A., & Tsai, L. (2010) · Neuron · doi:10.1016/j.neuron.2010.06.002 · Cited by 142 · see citing works
Glutamatergic dysfunction in schizophrenia: From basic neuroscience to clinical psychopharmacology
Paz, R. D., Tardito, S., Atzori, M., & Tseng, K. Y. (2008) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2008.06.005 · Cited by 142 · see citing works
Wang, Q., Charych, E. I., Pulito, V. L., Lee, J. B., Graziane, N., Crozier, R. A., Revilla-Sanchez, R., Kelly, M. P., Dunlop, A. J., Murdoch, H., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.87 · Cited by 141 · see citing works
Self-citationOberholzer, M., Marti, G., Barešić, M., Kunz, S., Hemphill, A. F., & Seebeck, T. (2006) · The FASEB Journal · doi:10.1096/fj.06-6818com · Cited by 139 · see citing works
Modeling cognitive endophenotypes of schizophrenia in mice
Kellendonk, C., Simpson, E. H., & Kandel, E. R. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.02.003 · Cited by 134 · see citing works
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Porteous, D. J., Millar, J. K., Brandon, N. J., & Sawa, A. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.09.002 · Cited by 137 · see citing works
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Acín‐Pérez, R., Russwurm, M., Günnewig, K., Gertz, M., Zoidl, G., Ramos, L. S., Buck, J., Levin, L. R., Rassow, J., Manfredi, G., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.266379 · Cited by 136 · see citing works
Paspalas, C. D., Wang, M., & Arnsten, A. F. T. (2013) · Cerebral Cortex · doi:10.1093/cercor/bhs152 · Cited by 136 · see citing works
Host Genetic Control of the Microbiota Mediates the Drosophila Nutritional Phenotype
Chaston, J. M., Dobson, A. J., Newell, P. D., & Douglas, A. E. (2015) · Applied and Environmental Microbiology · doi:10.1128/aem.03301-15 · Cited by 136 · see citing works
Scents and Nonsense: Olfactory Dysfunction in Schizophrenia
Turetsky, B. I., Hahn, C.-G., Borgmann‐Winter, K. E., & Moberg, P. J. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbp111 · Cited by 135 · see citing works
Kuroda, K., Yamada, S., Tanaka, M., Iizuka, M., Yano, H., Mori, D., Tsuboi, D., Nishioka, T., Namba, T., Iizuka, Y., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr400 · Cited by 135 · see citing works
Leliveld, S. R., Bader, V., Hendriks, P., Prikulis, I., Sajnani, G., Requena, J. R., & Korth, C. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5389-07.2008 · Cited by 133 · see citing works
PDE4B polymorphisms and decreased PDE4B expression are associated with schizophrenia
Fatemi, S. H., King, D. P., Reutiman, T. J., Folsom, T. D., Laurence, J. A., Lee, S. S., Fan, Y.-T., Paciga, S. A., Conti, M., & Menniti, F. S. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.01.029 · Cited by 133 · see citing works
Genetic Markers of Human Evolution Are Enriched in Schizophrenia
Srinivasan, S., Bettella, F., Mattingsdal, M., Wang, Y., Witoelar, A., Schork, A. J., Thompson, W. K., Zuber, V., Winsvold, B. S., Zwart, J.-A., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.10.009 · Cited by 129 · see citing works
DISC1: Structure, Function, and Therapeutic Potential for Major Mental Illness
Soares, D. C., Carlyle, B. C., Bradshaw, N. J., & Porteous, D. J. (2011) · ACS Chemical Neuroscience · doi:10.1021/cn200062k · Cited by 129 · see citing works
Self-citationGamo, N. J., & Arnsten, A. F. T. (2011) · Behavioral Neuroscience · doi:10.1037/a0023165 · Cited by 124 · see citing works
Hains, A. B., & Arnsten, A. F. T. (2008) · Learning & Memory · doi:10.1101/lm.921708 · Cited by 127 · see citing works
Increase in GSK3β gene copy number variation in bipolar disorder
Lachman, H. M., Pedrosa, E., Petruolo, O. A., Cockerham, M. S., Papolos, A., Novák, T., Papolos, D. F., & Stopková, P. (2007) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30498 · Cited by 127 · see citing works
Sachs, B. D., Baillie, G. S., McCall, J. R., Passino, M. A., Schachtrup, C., Wallace, D. A., Dunlop, A. J., MacKenzie, K. F., Klußmann, E., Lynch, M. J., et al. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200701040 · Cited by 126 · see citing works
Self-citationCommon DISC1 Polymorphisms Disrupt Wnt/GSK3β Signaling and Brain Development
Singh, K. K., Rienzo, G. D., Drane, L., Mao, Y., Flood, Z., Madison, J. M., Ferreira, M. A. R., Bergen, S. E., King, C. R., Sklar, P. B., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.030 · Cited by 125 · see citing works
Georgieva, L., Moskvina, V., Peirce, T., Norton, N., Bray, N. J., Jones, L., Holmans, P., MacGregor, S., Zammit, S., Wilkinson, J. C., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603029103 · Cited by 125 · see citing works
Human-Specific Histone Methylation Signatures at Transcription Start Sites in Prefrontal Neurons
Shulha, H. P., Crisci, J. L., Reshetov, D. A., Tushir, J. S., Cheung, I. K., Bharadwaj, R. A., Chou, H.-J., Houston, I. B., Peter, C. J., Mitchell, A., et al. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001427 · Cited by 123 · see citing works
- Authors
- Millar, J. K., Pickard, B. S., Mackie, S., James, R., Christie, S., Buchanan, S. R., Malloy, M. P., Chubb, J. E., Huston, E., Baillie, G. S., Thomson, P. A., Hill, E. V., Brandon, N. J., Rain, J.-C., Camargo, L. M., Whiting, P. J., Houslay, M. D., Blackwood, D. H. R., Muir, W. J., & Porteous, D. J.
- Affiliations
- Royal Edinburgh Hospital (GB)
- Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh EH4 2XU, UK.
- Corresponding author
- Millar, J. Kirsty
- ORCID
- Venue
- Science
- Published
- 2005-11-18
- Volume
- 310
- Issue
- 5751
- Pages
- 1187-1191
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2105051672
- Cited by
- 648
- References
- 20
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 12 · 2023: 11 · 2022: 14 · 2021: 13 · 2020: 14 · 2019: 19 · 2018: 21 · 2017: 24 · 2016: 28 · 2015: 47 · 2014: 39 · 2013: 24 · 2012: 35
- FWCI
- 20.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- DISC1, PDE4B, schizophrenia, cAMP signaling, phosphodiesterase 4, balanced translocation, protein-protein interaction, second messengers, genetic susceptibility, chronic mental illness
- MeSH terms
- Cyclic AMP, Adult, Affective Disorders, Psychotic, Animals, Cell Line, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 16, Enzyme Activation, Humans, Male, Nerve Tissue Proteins, Protein Binding, Schizophrenia, Translocation, Genetic, 3',5'-Cyclic-AMP Phosphodiesterases, Signal Transduction, Cadherins, Genetic Predisposition to Disease, Rats, Cyclic Nucleotide Phosphodiesterases, Type 4
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