TY  - JOUR
A1  - Chang, Hong
A1  - Hoshina, Naosuke
A1  - Zhang, Chen
A1  - Ma, Yina
A1  - Cao, Hongxin
A1  - Wang, Yaling
A1  - Wu, Dong-Dong
A1  - Bergen, Sarah E.
A1  - Landén, Mikael
A1  - Hultman, Christina M.
A1  - Preisig, Martin
A1  - Kutalik, Zoltán
A1  - Castelao, Enrique
A1  - Grigoroiu-Serbanescu, Maria
A1  - Forstner, Andreas Josef
A1  - Strohmaier, Jana
A1  - Hecker, Julian
A1  - Schulze, Thomas Gerd
A1  - Müller-Myhsok, Bertram
A1  - Reif, Andreas
A1  - Mitchell, Philip B.
A1  - Martin, Nicholas Gordon
A1  - Schofield, Peter R.
A1  - Cichon, Sven
A1  - Nöthen, Markus Maria
A1  - Walter, Henrik
A1  - Erk, Susanne
A1  - Heinz, Andreas
A1  - Amin, Najaf
A1  - Duijn, Cornelia M. van
A1  - Meyer-Lindenberg, Andreas
A1  - Tost, Heike
A1  - Xiao, Xiao
A1  - Yamamoto, Tadashi
A1  - Rietschel, Marcella
A1  - Li, Ming
T1  - The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders
T2  - Molecular psychiatry
N2  - 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.
KW  - Bipolar disorder
KW  - Depression
KW  - Genetics
KW  - Neuroscience
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/49143
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-491435
SN  - 1476-5578
SN  - 1359-4184
N1  - This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
VL  - 23
IS  - 2
SP  - 400
EP  - 412
PB  - Macmillan
CY  - London
ER  -