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| PMID |
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| TITLE |
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| The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders. |
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| ABSTRACT |
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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. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2016/06/07 |
| revised |
2016/10/27 |
| accepted |
2016/11/01 |
| pubmed |
2017/01/11 06:00 |
| medline |
2019/02/16 06:00 |
| entrez |
2017/01/11 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Chang H |
|
Chang |
H |
H |
|
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China. |
| Hoshina N |
|
Hoshina |
N |
N |
|
Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. |
| Zhang C |
|
Zhang |
C |
C |
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Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. |
| Ma Y |
|
Ma |
Y |
Y |
|
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China. |
| Cao H |
|
Cao |
H |
H |
|
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. |
| Wang Y |
|
Wang |
Y |
Y |
|
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. |
| Wu DD |
|
Wu |
D-D |
DD |
|
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. |
| Bergen SE |
|
Bergen |
S E |
SE |
|
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. |
| Landén M |
|
Landén |
M |
M |
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Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden. |
| Hultman CM |
|
Hultman |
C M |
CM |
|
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Preisig M |
|
Preisig |
M |
M |
|
Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland. |
| Kutalik Z |
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Kutalik |
Z |
Z |
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Swiss Institute of Bioinformatics, Lausanne, Switzerland. |
| Castelao E |
|
Castelao |
E |
E |
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Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland. |
| Grigoroiu-Serbanescu M |
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Grigoroiu-Serbanescu |
M |
M |
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Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania. |
| Forstner AJ |
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Forstner |
A J |
AJ |
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Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. |
| Strohmaier J |
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Strohmaier |
J |
J |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. |
| Hecker J |
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Hecker |
J |
J |
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Institute of Genomic Mathematics, University of Bonn, Bonn, Germany. |
| Schulze TG |
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Schulze |
T G |
TG |
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Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany. |
| Müller-Myhsok B |
|
Müller-Myhsok |
B |
B |
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University of Liverpool, Institute of Translational Medicine, Liverpool, UK. |
| Reif A |
|
Reif |
A |
A |
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Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany. |
| Mitchell PB |
|
Mitchell |
P B |
PB |
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Black Dog Institute, Sydney, NSW, Australia. |
| Martin NG |
|
Martin |
N G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Schofield PR |
|
Schofield |
P R |
PR |
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School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. |
| Cichon S |
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Cichon |
S |
S |
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Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Centre Jülich, Jülich, Germany. |
| Nöthen MM |
|
Nöthen |
M M |
MM |
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Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. |
|
Swedish Bipolar Study Group |
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MooDS Bipolar Consortium |
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| Walter H |
|
Walter |
H |
H |
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Department of Psychiatry and Psychotherapy, Universitätsmedizin Charité, Berlin, Germany. |
| Erk S |
|
Erk |
S |
S |
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Department of Psychiatry and Psychotherapy, Universitätsmedizin Charité, Berlin, Germany. |
| Heinz A |
|
Heinz |
A |
A |
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Department of Psychiatry and Psychotherapy, Universitätsmedizin Charité, Berlin, Germany. |
| Amin N |
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Amin |
N |
N |
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Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. |
| van Duijn CM |
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van Duijn |
C M |
CM |
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Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. |
| Meyer-Lindenberg A |
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Meyer-Lindenberg |
A |
A |
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Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. |
| Tost H |
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Tost |
H |
H |
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Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. |
| Xiao X |
|
Xiao |
X |
X |
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Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China. |
| Yamamoto T |
|
Yamamoto |
T |
T |
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Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan. |
| Rietschel M |
|
Rietschel |
M |
M |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. |
| Li M |
|
Li |
M |
M |
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Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China. |
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| INVESTIGATORS |
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| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Backlund |
Lena |
L |
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| Frisén |
Louise |
L |
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| Lavebratt |
Catharina |
C |
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| Schalling |
Martin |
M |
|
| Ösby |
Urban |
U |
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| Mühleisen |
Thomas W |
TW |
|
| Leber |
Markus |
M |
|
| Degenhardt |
Franziska |
F |
|
| Treutlein |
Jens |
J |
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| Mattheisen |
Manuel |
M |
|
| Maaser |
Anna |
A |
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| Meier |
Sandra |
S |
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| Herms |
Stefan |
S |
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| Hoffmann |
Per |
P |
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| Lacour |
André |
A |
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| Witt |
Stephanie H |
SH |
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| Streit |
Fabian |
F |
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| Lucae |
Susanne |
S |
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| Maier |
Wolfgang |
W |
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| Schwarz |
Markus |
M |
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| Vedder |
Helmut |
H |
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| Kammerer-Ciernioch |
Jutta |
J |
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| Pfennig |
Andrea |
A |
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| Bauer |
Michael |
M |
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| Hautzinger |
Martin |
M |
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| Wright |
Adam |
A |
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| Fullerton |
Janice M |
JM |
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| Montgomery |
Grant W |
GW |
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| Medland |
Sarah E |
SE |
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| Gordon |
Scott D |
SD |
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| Becker |
Tim |
T |
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| Schumacher |
Johannes |
J |
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| Propping |
Peter |
P |
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| JOURNAL |
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| VOLUME: 23 |
| ISSUE: 2 |
| TITLE: Molecular psychiatry |
| ISOABBREVIATION: Mol Psychiatry |
| YEAR: 2018 |
| MONTH: 02 |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1476-5578 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Mol Psychiatry |
| COUNTRY: England |
| ISSNLINKING: 1359-4184 |
| NLMUNIQUEID: 9607835 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Meta-Analysis |
| Research Support, Non-U.S. Gov't |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| MESH HEADINGS |
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| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
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| Amygdala |
physiopathology |
| Bipolar Disorder |
genetics |
| Brain |
physiopathology |
| Cadherins |
metabolism |
| Cognition |
physiology |
| Dendrites |
physiology |
| Dendritic Spines |
physiology |
| Depressive Disorder, Major |
genetics |
| Female |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Genotype |
genetics |
| Humans |
genetics |
| Male |
genetics |
| Middle Aged |
genetics |
| Mood Disorders |
genetics |
| Neuronal Plasticity |
genetics |
| Neurons |
genetics |
| Personality |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Risk Factors |
genetics |
| Synapses |
metabolism |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Cadherins |
| 0 |
protocadherin 17, human |
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| OTHER ID's |
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