The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders

Autor: 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
Přispěvatelé: 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
Jazyk: angličtina
Rok vydání: 2017
Předmět:
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
Zdroj: 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
ISSN: 1359-4184
DOI: 10.1038/mp.2016.231
Popis: 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.
Databáze: OpenAIRE
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