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The protocadherin 1...
The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders
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- Chang, H. (author)
- Karolinska Institutet
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Hoshina, N. (author)
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Zhang, C. (author)
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show more...
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Ma, Y. (author)
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Cao, H. (author)
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Wang, Y. (author)
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Wu, D. D. (author)
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- Bergen, S. E. (author)
- Karolinska Institutet
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- Landén, Mikael, 1966 (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Hultman, C. M. (author)
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Preisig, M. (author)
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Kutalik, Z. (author)
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Castelao, E. (author)
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Grigoroiu-Serbanescu, M. (author)
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Forstner, A. J. (author)
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Strohmaier, J. (author)
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Hecker, J. (author)
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Schulze, T. G. (author)
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Muller-Myhsok, B. (author)
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Reif, A. (author)
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Mitchell, P. B. (author)
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Martin, N. G. (author)
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Schofield, P. R. (author)
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Cichon, S. (author)
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Nothen, M. M. (author)
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Walter, H. (author)
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Erk, S. (author)
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Heinz, A. (author)
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Amin, N. (author)
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van Duijn, C. M. (author)
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Meyer-Lindenberg, A. (author)
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Tost, H. (author)
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Xiao, X. (author)
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Yamamoto, T. (author)
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Rietschel, M. (author)
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Li, M. (author)
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(creator_code:org_t)
- 2017-01-10
- 2018
- English.
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:2, s. 400-412
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https://www.nature.c...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- genome-wide association
- bipolar affective-disorder
- dendritic spine
- pathology
- educational-attainment
- hippocampal structure
- cadherin
- superfamily
- unipolar depression
- schizophrenia
- expression
- susceptibility
- Biochemistry & Molecular Biology
- Neurosciences & Neurology
- Psychiatry
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Chang, H.
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Hoshina, N.
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Zhang, C.
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Ma, Y.
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Cao, H.
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Wang, Y.
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show more...
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Wu, D. D.
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Bergen, S. E.
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Landén, Mikael, ...
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Hultman, C. M.
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Preisig, M.
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Kutalik, Z.
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Castelao, E.
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Grigoroiu-Serban ...
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Forstner, A. J.
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Strohmaier, J.
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Hecker, J.
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Schulze, T. G.
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Muller-Myhsok, B ...
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Reif, A.
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Mitchell, P. B.
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Martin, N. G.
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Schofield, P. R.
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Cichon, S.
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Nothen, M. M.
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Walter, H.
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Erk, S.
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Heinz, A.
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Amin, N.
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van Duijn, C. M.
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Meyer-Lindenberg ...
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Tost, H.
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Xiao, X.
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Yamamoto, T.
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Rietschel, M.
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Li, M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Psychiatry
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Molecular Psychi ...
- By the university
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University of Gothenburg
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Karolinska Institutet