The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders
| العنوان: | The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders |
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| المؤلفون: | H, Chang, N, Hoshina, C, Zhang, Y, Ma, H, Cao, Y, Wang, D-d, Wu, S E, Bergen, M, Landén, C M, Hultman, M, Preisig, Z, Kutalik, E, Castelao, M, Grigoroiu-Serbanescu, A J, Forstner, J, Strohmaier, J, Hecker, T G, Schulze, B, Müller-Myhsok, A, Reif, P B, Mitchell, N G, Martin, P R, Schofield, S, Cichon, M M, Nöthen, H, Walter, S, Erk, A, Heinz, N, Amin, C M, van Duijn, A, Meyer-Lindenberg, H, Tost, X, Xiao, T, Yamamoto, M, Rietschel, M, Li, Louise, Frisén, Catharina, Lavebratt, Lena, Backlund, Martin, Schalling, Urban, Ösby, Thomas W, Mühleisen, Markus, Leber, Franziska, Degenhardt, Jens, Treutlein, Manuel, Mattheisen, Anna, Maaser, Sandra, Meier, Stefan, Herms, Per, Hoffmann, André, Lacour, Stephanie H, Witt, Fabian, Streit, Susanne, Lucae, Wolfgang, Maier, Markus, Schwarz, Helmut, Vedder, Jutta, Kammerer-Ciernioch, Andrea, Pfennig, Michael, Bauer, Martin, Hautzinger, Adam, Wright, Janice M, Fullerton, Grant W, Montgomery, Sarah E, Medland, Scott D, Gordon, Tim, Becker, Johannes, Schumacher, Peter, Propping, Group, The Swedish Bipolar Study, D. S. Bipolar Consortium, Moo |
| المساهمون: | Swedish Bipolar Study Group, MooDS Bipolar Consortium, Backlund, L., Frisén, L., Lavebratt, C., Schalling, M., Ösby, U., Mühleisen, T.W., Leber, M., Degenhardt, F., Treutlein, J., Mattheisen, M., Maaser, A., Meier, S., Herms, S., Hoffmann, P., Lacour, A., Witt, S.H., Streit, F., Lucae, S., Maier, W., Schwarz, M., Vedder, H., Kammerer-Ciernioch, J., Pfennig, A., Bauer, M., Hautzinger, M., Wright, A., Fullerton, J.M., Montgomery, G.W., Medland, S.E., Gordon, S.D., Becker, T., Schumacher, J., Propping, P., Epidemiology, The Swedish Bipolar Study Group |
| المصدر: | Molecular psychiatry, vol. 23, no. 2, pp. 400-412 Molecular Psychiatry, 23(2), 400-412. Nature Publishing Group Molecular Psychiatry MOLECULAR PSYCHIATRY Molecular psychiatry 23, 400–412 (2018). doi:10.1038/mp.2016.231 |
| بيانات النشر: | Springer Nature, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Dendritic spine, Bipolar Disorder, Genotype, Dendritic Spines, Genome-wide association study, Amygdala, Polymorphism, Single Nucleotide, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cognition, Risk Factors, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, ddc:610, Molecular Biology, Neurons, Depressive Disorder, Major, Neuronal Plasticity, Mood Disorders, Brain, Dendrites, Middle Aged, medicine.disease, Cadherins, 3. Good health, Psychiatry and Mental health, 030104 developmental biology, medicine.anatomical_structure, Mood disorders, Schizophrenia, Synapses, Major depressive disorder, Original Article, Female, Psychopharmacology, Psychology, Neuroscience, Personality, Amygdala/physiopathology, Bipolar Disorder/genetics, Brain/physiopathology, Cadherins/genetics, Cadherins/metabolism, Cognition/physiology, Depressive Disorder, Major/genetics, Genetic Predisposition to Disease/genetics, Mood Disorders/genetics, Personality/genetics, Polymorphism, Single Nucleotide/genetics, Synapses/genetics, Synapses/metabolism |
| الوصف: | Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes. |
| وصف الملف: | application/pdf; application/octet-stream |
| اللغة: | English |
| تدمد: | 1359-4184 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e3291c94015d4c14d6abc52a67d066bTest http://id.nii.ac.jp/1394/00001109Test/ |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6e3291c94015d4c14d6abc52a67d066b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13594184 |
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