The DISC locus in psychiatric illness
Abstract
The DISC locus is located at the breakpoint of a balanced t(1;11) chromosomal translocation in a large and unique Scottish family. This translocation segregates in a highly statistically significant manner with a broad diagnosis of psychiatric illness, including schizophrenia, bipolar disorder and major depression, as well as with a narrow diagnosis of schizophrenia alone. Two novel genes were identified at this locus and due to the high prevalence of schizophrenia in this family, they were named Disrupted-in-Schizophrenia-1 (DISC1) and Disrupted-in-Schizophrenia-2 (DISC2). DISC1 encodes a novel multifunctional scaffold protein, whereas DISC2 is a putative noncoding RNA gene antisense to DISC1. A number of independent genetic linkage and association studies in diverse populations support the original linkage findings in the Scottish family and genetic evidence now implicates the DISC locus in susceptibility to schizophrenia, schizoaffective disorder, bipolar disorder and major depression as well as various cognitive traits. Despite this, with the exception of the t(1;11) translocation, robust evidence for a functional variant(s) is still lacking and genetic heterogeneity is likely. Of the two genes identified at this locus, DISC1 has been prioritized as the most probable candidate susceptibility gene for psychiatric illness, as its protein sequence is directly disrupted by the translocation. Much research has been undertaken in recent years to elucidate the biological functio…
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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 [120]
Loss-of-function mutations in DISC1 are associated with a variety of mental illnesses, especially an increased incidence of depression.
“As loss-of-function mutations in DISC1 are associated with a variety of mental illnesses, especially an increased incidence of depression120, loss of spines may contribute to a variety of disorders, with symptoms related to the subcircuit(s) most affected—for example, changes in vmPFC increasing risk of depression and impairment of dlPFC circuits increasing risk of schizophrenia.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [120]
Cites
MACDONALD, M. (1993) · Cell · doi:10.1016/0092-8674(93)90585-e · Cited by 8,366 · see citing works
DISC1 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
Self-citationSynaptic plasticity and mood disorders
Duman, R. S. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001016 · Cited by 363 · 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
Tardito, D., Perez, J., Tiraboschi, E., Musazzi, L., Racagni, G., & Popoli, M. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.1.7 · Cited by 303 · see citing works
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Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800 · see citing works
Genetic Heterogeneity in Human Disease
McClellan, J., & King, M.-C. (2010) · Cell · doi:10.1016/j.cell.2010.03.032 · Cited by 981 · 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
Dendritic spine pathology in schizophrenia
Glausier, J. R., & Lewis, D. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.04.044 · Cited by 581 · 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
Linking oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in schizophrenia
Takahashi, N., Sakurai, T., Davis, K. L., & Buxbaum, J. D. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.09.004 · Cited by 337 · see citing works
Kim, J. Y., Duan, X., Liu, C. Y., Jang, M.-H., Guo, J. U., Pow-anpongkul, N., Kang, E., Song, H., & Ming, G.-L. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.008 · Cited by 319 · see citing works
Is Glycogen Synthase Kinase-3 a Central Modulator in Mood Regulation?
Li, X., & Jope, R. S. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.105 · Cited by 294 · see citing works
CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease
Bhat, S., Dao, D. T., Terrillion, C. E., Arad, M., Smith, R. J., Soldatov, N. M., & Gould, T. D. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.06.001 · Cited by 271 · 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
Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology
Abazyan, B., Nomura, J., Kannan, G., Ishizuka, K., Tamashiro, K. L., Nucifora, F., Pogorelov, V., Ladenheim, B., Yang, C., Krasnova, I. N., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.022 · Cited by 255 · see citing works
An epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy
Millan, M. J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.11.015 · Cited by 229 · see citing works
Understanding the Role of DISC1 in Psychiatric Disease and during Normal Development
Brandon, N. J., Millar, J. K., Korth, C., Sive, H., Singh, K. K., & Sawa, A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3355-09.2009 · Cited by 198 · see citing works
Self-citationMaternal immune activation in neurodevelopmental disorders
Solek, C. M., Farooqi, N., Verly, M., Lim, T. K., & Ruthazer, E. S. (2018) · Developmental Dynamics · doi:10.1002/dvdy.24612 · Cited by 168 · see citing works
Ayhan, 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
Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood
Ibi, D., Nagai, T., Koike, H., Kitahara, Y., Mizoguchi, H., Niwa, M., Jaaro-Peled, H., Nitta, A., Yoneda, Y., & Nabeshima, T. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.08.027 · Cited by 137 · see citing works
“We chose DISC1 as a genetic factor on which to focus, because its role during neurodevelopment is well characterized [6,13].”
BackgroundAnimal models of bipolar mania: The past, present and future
Logan, R. W., & McClung, C. A. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.08.041 · Cited by 136 · 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-citationHains, A. B., & Arnsten, A. F. T. (2008) · Learning & Memory · doi:10.1101/lm.921708 · Cited by 127 · see citing works
Genetic contributions to behavioural diversity at the gene-environment interface
Bendesky, A., & Bargmann, C. I. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3065 · Cited by 103 · see citing works
Common variant at 16p11.2 conferring risk of psychosis
Steinberg, S., de Jong, S., Mattheisen, M., Costas, J., Demontis, D., Jamain, S., Pietiläinen, O. P. H., Lin, K., Papiol, S., Huttenlocher, J., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2012.157 · Cited by 104 · see citing works
The Role of DNA Copy Number Variation in Schizophrenia
Tam, G. W. C., Redon, R., Carter, N. P., & Grant, S. G. N. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.07.027 · Cited by 98 · see citing works
Translational research in bipolar disorder: emerging insights from genetically based models
Chen, G., Henter, I. D., & Manji, H. K. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.3 · Cited by 95 · see citing works
Schumacher, J., Laje, G., Jamra, R. A., Becker, T., Mühleisen, T. W., Vasilescu, C., Mattheisen, M., Herms, S., Hoffmann, P., Hillmer, A. M., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp204 · Cited by 86 · see citing works
The effects of arousal on apical amplification and conscious state
Phillips, W. A., Larkum, M. E., Harley, C. W., & Silverstein, S. M. (2016) · Neuroscience of Consciousness · doi:10.1093/nc/niw015 · Cited by 75 · see citing works
Chen, S.-Y., Huang, P.-H., & Cheng, H.-J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018128108 · Cited by 73 · see citing works
Bader, V., Tomppo, L., Trossbach, S. V., Bradshaw, N. J., Prikulis, I., Leliveld, S. R., Lin, C.-Y., Ishizuka, K., Sawa, A., Ramos, A., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds273 · Cited by 70 · see citing works
Self-citationAn Emerging Role for Long Non-Coding RNA Dysregulation in Neurological Disorders
Fenoglio, C., Ridolfi, E., Galimberti, D., & Scarpini, E. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141020427 · Cited by 68 · see citing works
Tereshko, L., Gao, Y., Cary, B. A., Turrigiano, G. G., & Sengupta, P. (2021) · eLife · doi:10.7554/elife.65427 · Cited by 60 · see citing works
Genetic Markers of Comorbid Depression and Alcoholism in Women
Procopio, D. O., Saba, L. M., Walter, H., Lesch, O., Skala, K., Schlaff, G., Vanderlinden, L., Clapp, P., Hoffman, P. L., & Tabakoff, B. (2013) · Alcoholism: Clinical and Experimental Research · doi:10.1111/acer.12060 · Cited by 52 · see citing works
Wessman, J., Paunio, T., Tuulio-Henriksson, A., Koivisto, M., Partonen, T., Suvisaari, J., Turunen, J. A., Wedenoja, J., Hennah, W., Pietiläinen, O. P. H., et al. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.05.034 · Cited by 52 · see citing works
Abnormal interneuron development in disrupted-in-schizophrenia-1 L100P mutant mice
Lee, F. H., Zai, C. C., Cordes, S. P., Roder, J. C., & Wong, A. H. (2013) · Molecular Brain · doi:10.1186/1756-6606-6-20 · Cited by 49 · see citing works
Role of disrupted in schizophrenia 1 (DISC1) in stress-induced prefrontal cognitive dysfunction
Gamo, N. J., Duque, A., Paspalas, C. D., Kata, A., Fine, R., Boven, L., Bryan, C., Lo, T., Anighoro, K., Bermudez, L., et al. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.104 · Cited by 37 · see citing works
Rajkumar, A. P., Christensen, J. H., Mattheisen, M., Jacobsen, I., Bache, I., Pallesen, J., Grove, J., Qvist, P., McQuillin, A., Gurling, H. M., et al. (2015) · Bipolar Disorders · doi:10.1111/bdi.12239 · Cited by 24 · see citing works
- Authors
- Chubb, J. E., Bradshaw, N. J., Soares, D. C., Porteous, D. J., & Millar, J. K.
- Affiliations
- Western General Hospital (GB)
- Corresponding author
- Millar, J K
- Venue
- Molecular Psychiatry
- Published
- 2007-10-02
- Volume
- 13
- Issue
- 1
- Pages
- 36-64
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2047679528
- Cited by
- 542
- References
- 5
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 11 · 2023: 6 · 2022: 9 · 2021: 14 · 2020: 18 · 2019: 17 · 2018: 20 · 2017: 22 · 2016: 33 · 2015: 40 · 2014: 32 · 2013: 32 · 2012: 56
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- DISC1, schizophrenia, bipolar disorder, major depressive disorder, schizoaffective disorder, scaffold proteins, genetic linkage, genetic association, brain development, cytoskeletal function, cAMP signaling, genetic heterogeneity, cognitive characteristics
- MeSH terms
- Animals, Mental Disorders, Humans, Genetic Linkage, Nerve Tissue Proteins, RNA, Messenger, Genetic Predisposition to Disease, RNA, Long Noncoding
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