Role of disrupted in schizophrenia 1 (DISC1) in stress-induced prefrontal cognitive dysfunction
Open accessAbstract
Recent genetic studies have linked mental illness to alterations in disrupted in schizophrenia 1 (DISC1), a multifunctional scaffolding protein that regulates cyclic adenosine monophosphate (cAMP) signaling via interactions with phosphodiesterase 4 (PDE4). High levels of cAMP during stress exposure impair function of the prefrontal cortex (PFC), a region gravely afflicted in mental illness. As stress can aggravate mental illness, genetic insults to DISC1 may worsen symptoms by increasing cAMP levels. The current study examined whether viral knockdown (KD) of the Disc1 gene in rat PFC increases susceptibility to stress-induced PFC dysfunction. Rats were trained in a spatial working memory task before receiving infusions of (a) an active viral construct that knocked down Disc1 in PFC (DISC1 KD group), (b) a 'scrambled' construct that had no effect on Disc1 (Scrambled group), or (c) an active construct that reduced DISC1 expression dorsal to PFC (Anatomical Control group). Data were compared with an unoperated Control group. Cognitive performance was assessed following mild restraint stress that had no effect on normal animals. DISC1 KD rats were impaired by 1 h restraint stress, whereas Scrambled, Control, and Anatomical Control groups were unaffected. Thus, knocking down Disc1 in PFC reduced the threshold for stress-induced cognitive dysfunction, possibly through disinhibited cAMP signaling at neuronal network synapses. These findings may explain why patients with DISC1 mutations may be especially vulnerable to the effects of stress.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Knockdown of DISC1 in rodent PFC increases sensitivity to stress-induced PFC cognitive deficits.
“Knockdown of DISC1 in rodent PFC increases cAMP signaling in PFC neurons129 and increases sensitivity to stress-induced PFC cognitive deficits130.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [130]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
An Integrative Theory of Prefrontal Cortex Function
Miller, E. K., & Cohen, J. D. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.167 · Cited by 12,803 · see citing works
Deep Brain Stimulation for Treatment-Resistant Depression
Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., Schwalb, J. M., & Kennedy, S. H. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.014 · Cited by 4,059 · 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
Self-citationCellular basis of working memory
Goldman-Rakic, P. S. (1995) · Neuron · doi:10.1016/0896-6273(95)90304-6 · Cited by 2,663 · see citing works
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
Goldman-Rakic, P. S. (1996) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1996.0129 · Cited by 1,072 · see citing works
Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory
Vijayraghavan, S., Wang, M., Birnbaum, S. G., Williams, G. V., & Arnsten, A. F. T. (2007) · Nature Neuroscience · doi:10.1038/nn1846 · Cited by 1,013 · see citing works
Self-citationZahrt, J., Taylor, J. R., Mathew, R. G., & Arnsten, A. F. T. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-21-08528.1997 · Cited by 796 · see citing works
Self-citationCognition in schizophrenia: core psychological and neural mechanisms
Barch, D. M., & Ceaser, A. E. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.11.015 · Cited by 752 · see citing works
Blackwood, 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
Association within a family of a balanced autosomal translocation with major mental illness
St Clair, D., Blackwood, D., Muir, W., Walker, M., St Clair, D., Muir, W., Carothers, A., Spowart, G., Gosden, C., & Evans, H. J. (1990) · The Lancet · doi:10.1016/0140-6736(90)91520-k · Cited by 727 · see citing works
Pathways modulating neural KCNQ/M (Kv7) potassium channels
Delmas, P., & Brown, D. A. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1785 · Cited by 686 · 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
Self-citationDISC1 and PDE4B Are Interacting Genetic Factors in Schizophrenia That Regulate cAMP Signaling
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., et al. (2005) · Science · doi:10.1126/science.1112915 · Cited by 648 · see citing works
Relation of Prefrontal Cortex Dysfunction to Working Memory and Symptoms in Schizophrenia
Perlstein, W. M., Carter, C. S., Noll, D. C., & Cohen, J. D. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.7.1105 · Cited by 647 · 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
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
Self-citationDisrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain
Duan, X., Chang, J. H., Ge, S., Faulkner, R. L., Kim, J. Y., Kitabatake, Y., Liu, X.-B., Yang, C.-H., Jordan, J. D., Ma, D. K., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.010 · Cited by 538 · see citing works
A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development
Kamiya, A., Kubo, K., Tomoda, T., Takaki, M., Youn, R., Ozeki, Y., Sawamura, N., Park, U., Kudo, C., Okawa, M., et al. (2005) · Nature Cell Biology · doi:10.1038/ncb1328 · Cited by 531 · see citing works
Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia
Callicott, J. H., Straub, R. E., Pezawas, L., Egan, M. F., Mattay, V. S., Hariri, A. R., Verchinski, B. A., Meyer‐Lindenberg, A., Balkissoon, R., Kolachana, B. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500515102 · Cited by 512 · see citing works
Wang, M., Yang, Y., Wang, C.-J., Gamo, N. J., Jin, L. E., Mazer, J. A., Morrison, J. H., Wang, X.-J., & Arnsten, A. F. T. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.032 · Cited by 489 · see citing works
Self-citationA Functional Magnetic Resonance Imaging Study of Bipolar Disorder
Blumberg, H. P., Leung, H., Skudlarski, P., Lacadie, C., Fredericks, C. A., Harris, B. C., Charney, D. S., Gore, J. C., Krystal, J. H., & Peterson, B. S. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.6.601 · Cited by 475 · see citing works
Hodgkinson, C. A., Goldman, D. A., Jaeger, J., Persaud, S. D., Kane, J. M., Lipsky, R. H., & Malhotra, A. K. (2004) · The American Journal of Human Genetics · doi:10.1086/425586 · Cited by 437 · see citing works
Linking 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
Hikida, 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
Rao, S. G., Williams, G. V., & Goldman-Rakic, P. S. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-01-00485.2000 · Cited by 407 · 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
Ozeki, Y., Tomoda, T., Kleiderlein, J. J., Kamiya, A., Bord, L., Fujii, K., Okawa, M., Yamada, N., Hatten, M. E., Snyder, S. H., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0136913100 · Cited by 388 · see citing works
Cannon, T. D., Hennah, W., van Erp, T. G. M., Thompson, P. M., Lonnqvist, J., Huttunen, M., Gasperoni, T., Tuulio-Henriksson, A., Pirkola, T., Toga, A. W., et al. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.11.1205 · Cited by 337 · see citing works
Rao, S. G., Williams, G. V., & Goldman, P. S. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.81.4.1903 · Cited by 335 · 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
Niwa, M., Kamiya, A., Murai, R., Kubo, K., Gruber, A. J., Tomita, K., Lu, L., Tomisato, S., Jaaro-Peled, H., Seshadri, S., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.019 · Cited by 291 · see citing works
Disc1 is mutated in the 129S6/SvEv strain and modulates working memory in mice
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
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
Hashimoto, 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
Li, W., Zhou, Y., Jentsch, J. D., Brown, R. A. M., Tian, X., Ehninger, D., Hennah, W., Peltonen, L., Lönnqvist, J. K., HUTTUNEN, M. O., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706900104 · Cited by 207 · see citing works
Arnsten, A. F. T. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhm033 · Cited by 200 · see citing works
Self-citationAssociation of DISC1 with autism and Asperger syndrome
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
A Review of Disrupted-in-Schizophrenia-1 (disc1): Neurodevelopment, Cognition, and Mental Conditions
Ishizuka, K., Paek, M., Kamiya, A., & Sawa, A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.065 · Cited by 190 · see citing works
The Genetics and Biology of Disc1—An Emerging Role in Psychosis and Cognition
Porteous, D. J., Thomson, P. A., Brandon, N. J., & Millar, J. K. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.008 · Cited by 172 · see citing works
Dynamic network connectivity: a new form of neuroplasticity
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
Self-citationHennah, W., Tuulio‐Henriksson, A., Paunio, T., Ekelund, J., Varilo, T., Partonen, T., Cannon, T. D., Lönnqvist, J. K., & Peltonen, L. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001731 · Cited by 156 · 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
Stress reactivity in bipolar patients and its relation to prior history of disorder
(1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.6.856 · Cited by 138 · 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
Self-citationGamo, N. J., & Arnsten, A. F. T. (2011) · Behavioral Neuroscience · doi:10.1037/a0023165 · Cited by 124 · see citing works
Self-citationDisc1 Point Mutations in Mice Affect Development of the Cerebral Cortex
Lee, F. H. F., Fadel, M. P., Preston-Maher, K., Cordes, S. P., Clapcote, S. J., Price, D. J., Roder, J., & Wong, A. H. C. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4219-10.2011 · Cited by 123 · see citing works
(1995) · American Psychiatric Press eBooks · Cited by 118 · see citing works
The effects of sex and hormonal status on restraint-stress-induced working memory impairment
Shansky, R. M., Rubinow, K., Brennan, A., & Arnsten, A. F. (2006) · Behavioral and Brain Functions · doi:10.1186/1744-9081-2-8 · Cited by 107 · see citing works
Self-citationMillar, J. K., Mackie, S., Clapcote, S. J., Murdoch, H., Pickard, B. S., Christie, S., Muir, W. J., Blackwood, D., Roder, J., Houslay, M. D., et al. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.140210 · Cited by 106 · see citing works
DISC1 and neurocognitive function in schizophrenia
Burdick, K. E., Hodgkinson, C. A., Szeszko, P. R., Lencz, T., Ekholm, J. M., Kane, J. M., Goldman, D. A., & Malhotra, A. K. (2005) · Neuroreport · doi:10.1097/01.wnr.0000175248.25535.f6 · Cited by 105 · see citing works
MacGregor, S., Visscher, P. M., Knott, S., Thomson, P. A., Porteous, D. J., Millar, J. K., Devon, R. S., Blackwood, D., & Muir, W. J. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001544 · Cited by 102 · see citing works
Disrupted In Schizophrenia 1 (DISC1): Subcellular targeting and induction of ring mitochondria
Millar, J. K., James, R., Christie, S., & Porteous, D. J. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.08.021 · Cited by 96 · see citing works
DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia
Szeszko, P. R., Hodgkinson, C. A., Robinson, D. G., DeRosse, P., Bilder, R. M., Lencz, T., Burdick, K. E., Napolitano, B., Betensky, J. D., Kane, J. M., et al. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2007.10.011 · Cited by 95 · see citing works
Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes
Carless, M. A., Glahn, D. C., Johnson, M. P., Curran, J. E., Bozaoglu, K., Dyer, T. D., Winkler, A. M., Cole, S. A., Almasy, L. A., MacCluer, J. W., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.37 · Cited by 84 · see citing works
Hennah, W., & Porteous, D. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004906 · Cited by 79 · see citing works
Murray, R. M. (1992) · Behaviour Research and Therapy · doi:10.1016/0005-7967(92)90085-u · Cited by 53 · see citing works
Two Genes Link Two Distinct Psychoses
Sawa, A., & Snyder, S. H. (2005) · Science · doi:10.1126/science.1121114 · Cited by 51 · see citing works
The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain morphology in schizophrenia
Takahashi, T., Suzuki, M., Tsunoda, M., Maeno, N., Kawasaki, Y., Zhou, S.-Y., Hagino, H., Niu, L., Tsuneki, H., Kobayashi, S., et al. (2009) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2009.01.005 · Cited by 48 · see citing works
Raznahan, A., Lee, Y., Long, R. T. L., GREENSTEIN, D. K., CLASEN, L. S., Addington, A. M., Rapoport, J. L., & Giedd, J. N. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.72 · Cited by 42 · see citing works
Song, W., Li, W., Noltner, K., Jin, Y., Green, E., Grozeva, D., Jones, I. R., Craddock, N. J., Longmate, J., Feng, J., et al. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.09.027 · Cited by 28 · see citing works
Variation in DISC1 is associated with anxiety, depression and emotional stability in elderly women
Harris, S. E., Hennah, W., Thomson, P. A., Michelle Luciano, A., Starr, J. M., Porteous, D. J., & Deary, I. J. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.88 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Self-citationThe 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
“Impairment of DISC1 reduces its ability to anchor PDE4A, and this in turn leads to a disinhibition of the stress response and accompanying PFC impairment (108).”
Neurodevelopment, GABA System Dysfunction, and Schizophrenia
Schmidt, M. J., & Mirnics, K. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.95 · Cited by 239 · see citing works
Gundersen, V., Storm‐Mathisen, J., & Bergersen, L. H. (2015) · Physiological Reviews · doi:10.1152/physrev.00024.2014 · Cited by 172 · see citing works
Abbott, P. W., Gumusoglu, S. B., Bittle, J., Beversdorf, D. Q., & Stevens, H. E. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.01.019 · Cited by 109 · see citing works
Molecular Influences on Working Memory Circuits in Dorsolateral Prefrontal Cortex
Arnsten, A. F. T., & Jin, L. E. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-420170-5.00008-8 · Cited by 79 · see citing works
Self-citationThe genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex
Arnsten, A. F. T., Datta, D., & Wang, M. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-00973-3 · Cited by 76 · see citing works
Self-citationJin, L. E., Wang, M., Yang, S.-T., Yang, Y., Galvin, V. C., Lightbourne, T. C., Ottenheimer, D. J., Zhong, Q., Stein, J., Raja, A., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.129 · Cited by 57 · see citing works
“45, 46 Insults to DISC1 and PDE4A are linked to increased risk of illness.”
Self-citationSchizophrenia and neurogenesis: A stem cell approach.
Iannitelli, A., Quartini, A., Tirassa, P., & Bersani, G. (2017) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.06.010 · Cited by 42 · see citing works
Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia
Lee, S.-A., & Huang, K.-C. (2016) · BMC Medical Genomics · doi:10.1186/s12920-016-0229-y · Cited by 46 · see citing works
Arnsten, A. F. T., Woo, E., Yang, S., Wang, M., & Datta, D. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.02.003 · Cited by 35 · see citing works
“DISC1 knockdown in rat medial PFC lowered the threshold for stress-induced deficits in working memory, with no effect under nonstress conditions (94).”
Self-citationDatta, D., & Arnsten, A. F. T. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00505 · Cited by 36 · see citing works
Self-citationPDE Inhibitors for the Treatment of Schizophrenia
Snyder, G. L., & Vanover, K. E. (2017) · Advances in neurobiology · doi:10.1007/978-3-319-58811-7_14 · Cited by 36 · see citing works
Xu, Y., Cao, W., Zhou, M., Li, C.-Q., Luo, Y., Wang, H., Zhao, R., Jiang, S., Yang, J., Liu, Y., et al. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.02.031 · Cited by 30 · see citing works
“[8] Gamo NJ, Duque A, Paspalas CD, Kata A, Fine R, Boven L, et al.”
BackgroundKassan, A., Egawa, J., Zhang, Z., Almenar‐Queralt, A., Nguyen, Q. M., Lajevardi, Y., Kim, K., Posadas, E., Jeste, D. V., Roth, D. M., et al. (2016) · Journal of Neurophysiology · doi:10.1152/jn.00481.2016 · Cited by 29 · see citing works
“, PDE4) in postsynaptic densities (Bradshaw et al. 2011; Gamo et al. 2013; Soda et al. 2013; Wang et al. 2008).”
BackgroundEl-Hassar, L., Simen, A. A., Duque, A., Patel, K. D., Kaczmarek, L. K., Arnsten, A. F. T., & Yeckel, M. F. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.12.019 · Cited by 30 · see citing works
Self-citationSynaptic dysfunction in schizophrenia
Mısır, E., & Akay, G. G. (2023) · Synapse · doi:10.1002/syn.22276 · Cited by 29 · see citing works
“Unanchoring with PDE4 that occurs in DISC1 mutation results in an increase in cAMP level, activation of HCN channel, and thus deterioration in prefrontal cortex function (Gamo et al., 2013).”
BackgroundExpression of Behavioral Phenotypes in Genetic and Environmental Mouse Models of Schizophrenia
Sultana, R., & Lee, C. C. (2020) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.00029 · Cited by 23 · see citing works
“Due to its synaptic localization with PDE4 and HCN channels it plays a vital role in maintaining working memory and other related behavioral phenotypes (Niwa et al., 2010; Gamo et al., 2013; Paspalas et al., 2013).”
Backgroundde Bartolomeis, A., Avagliano, C., Vellucci, L., D'Ambrosio, L., Manchia, M., D'Urso, G., Buonaguro, E., & Iasevoli, F. (2019) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.08.019 · Cited by 17 · see citing works
Olivero, P., Lozano, C., Sotomayor‐Zárate, R., Meza-Concha, N., Marcelo Arancibia, M., Córdova, C., González‐Arriagada, W. A., Ramírez-Barrantes, R., & Marchant, I. (2018) · Neural Plasticity · doi:10.1155/2018/6798712 · Cited by 20 · see citing works
“Disrupted in schizophrenia 1 (DISC1) is a scaffold protein involved in the regulation of neuronal proliferation, differentiation, migration, and cytoskeletal modulation [70] which has been extensively linked to schizophrenia and other major mental illnesses [71–73].”
BackgroundGender-Specific Associations betweenCHGBGenetic Variants and Schizophrenia in a Korean Population
Shin, J.-G., Kim, J., Park, C. S., Kim, B., Kim, J., Choi, I., Hwang, J., Shin, H. D., & Woo, S.-I. (2017) · Yonsei Medical Journal · doi:10.3349/ymj.2017.58.3.619 · Cited by 19 · see citing works
BDNF+/− rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders
Martis, L., Wiborg, O., Holmes, M. C., & Harris, A. P. (2018) · Genes Brain & Behavior · doi:10.1111/gbb.12546 · Cited by 18 · see citing works
Hikida, T., Morita, M., Kuroiwa, M., Macpherson, T., Shuto, T., Sotogaku, N., Niwa, M., Sawa, A., & Nishi, A. (2019) · Neuroscience Research · doi:10.1016/j.neures.2019.02.007 · Cited by 12 · see citing works
“Phosphodiesterase-4 (PDE4) is an important factor in the DISC1 interactome (Millar et al., 2005; Carlyle et al., 2011; Hikida et al., 2012; Gamo et al., 2013).”
BackgroundDisrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia
Norlelawati, A. T., Abdullah, K., Norsidah, K.-Z., Ramli, M., Tariq, A. R., & Taib, W. R. W. (2015) · Psychiatry Investigation · doi:10.4306/pi.2015.12.1.103 · Cited by 10 · see citing works
The Toxoplasma gondii Model of Schizophrenia
Webster, J. P., Lamberton, P. H. L., & McConkey, G. A. (2015) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-800981-9.00014-6 · Cited by 9 · see citing works
Deng, D., Jian, C., Lei, L., Zhou, Y., McSweeney, C., Dong, F., Shen, Y., Zou, D., Wang, Y., Wu, Y., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.21381 · Cited by 9 · see citing works
“Different from the approaches used in many other DISC1 mouse models [35, 36, 42-45], we directly targeted nestin positive NPCs with inducible DN-DISC1.”
BackgroundMethodBrandon, N. J. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.09.019 · Cited by 6 · see citing works
Ahmed, M. K., Abdou, K., Ibrahim, W. W., Mohamed, A. F., & El-Boghdady, N. A. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06940-6 · Cited by 4 · see citing works
“These aggregates disrupt dopamine signaling, cAMP signaling, and cytoskeletal architecture, leading to synaptic dysfunction and neurodevelopmental anomalies in schizophrenia ( Gamo et al. 2013; Trossbach et al. 2016).”
Zhang, B.-L., Chen, Y., Zhang, Y., Qiao, Y., Wu, Y., Zhang, Y., Lu, Y., You, X., Li, Y., Huang, H.-D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63747-x · Cited by 4 · see citing works
Wang, M., & Arnsten, A. F. T. (2015) · PubMed Central · doi:10.13918/j.issn.2095-8137.2015.6.314 · Cited by 4 · see citing works
“For example, viral knockdown of DISC1 (Disrupted In SChizophrenia) in rat medial PFC lowers the threshold for stress-induced PFC dysfunction, possibly by unanchoring PDE4A and dysregulating cAMP signaling (Gamo et al, 2013).”
BackgroundSelf-citationBriones-Aranda, A., Suárez-Santiago, J. E., Castellanos-Pérez, M., & Villa, V. M. V. (2015) · Psiquiatría Biológica · doi:10.1016/j.psiq.2015.03.001 · Cited by 2 · see citing works
Kay, L., Sangal, V., Black, G. W., & Soundararajan, M. (2018) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-018-3389-6 · Cited by 2 · see citing works
“Even more interestingly, DISC1 has been linked to stress-induced psychosis in schizophrenic individuals [24], a clinical feature that is presented more frequent in patients harbouring specific NEDD4 genotypes [21].”
Evaluation and characterisation of two zebrafish models of schizophrenia
Daggett, J. M. (2016) · St Andrews Research Repository (St Andrews Research Repository) · Cited by 2 · see citing works
Volgin, A. D., Cheresiz, S. V., Chizhova, N. D., Smirnova, K. V., Doroshkov, A. V., Galstya, D. S., de Abreu, M. S., Strekalova, T. V., Lipina, T. V., Pletnikov, M. V., et al. (2025) · Journal of Integrative Neuroscience · doi:10.31083/jin43162 · Cited by 1 · see citing works
“In Disc1 knockdown rats, a 1-h restraint stress impairs working memory, whereas in non-stressful conditions, the loss of Disc1 has no effects [127].”
Wang, M., Galvin, V. C., Joyce, M. K. P., Datta, D., Yang, S., Disney, A. A., & Arnsten, A. F. T. (2026) · Biological Psychiatry · doi:10.1016/j.biopsych.2026.06.008 · Cited by 1 · see citing works
Self-citationTwo Novel Photoactivatable Phosphodiesterases to Independently Hydrolyze cAMP and cGMP
Bergin, F. (2017) · TSpace (University of Toronto)
Arnsten, A. F. T. (2020) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780190069162.013.4
Self-citation
- Authors
- Gamo, N. J., Duque, A., Paspalas, C. D., Kata, A., Fine, R., Boven, L., Bryan, C., Lo, T., Anighoro, K., Bermudez, L., Peng, K., Annor, A., Raja, A., Mansson, E., Taylor, S. R., Patel, K., Simen, A. A., & Arnsten, A. F. T.
- Affiliations
- Yale University (US)
- Corresponding author
- Gamo, N J
- Venue
- Translational Psychiatry
- Published
- 2013-12-03
- Volume
- 3
- Issue
- 12
- Pages
- e328-e328
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4030323
- OpenAlex
- W2157444024
- Cited by
- 37
- References
- 64
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 1 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 3
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Translational Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute on Alcohol Abuse and Alcoholism (RL1AA017536)
- National Institute on Aging (P01AG030004)
- National Institute of Neurological Disorders and Stroke (NS-07224, T32 NS07224, T32NS007224)
- National Center for Research Resources (U54RR024350)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- DISC1, schizophrenia, prefrontal cortex, cAMP signaling, phosphodiesterase 4, restraint stress, spatial working memory, gene disruption
- MeSH terms
- Cyclic AMP, Animals, Cognition Disorders, Disease Models, Animal, Male, Memory, Short-Term, Nerve Tissue Proteins, Restraint, Physical, Schizophrenia, Stress, Psychological, Synapses, Signal Transduction, Rats, Sprague-Dawley, Prefrontal Cortex, Rats, Gene Knockdown Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
