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| PMID |
|
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| TITLE |
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| Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders. |
|
| ABSTRACT |
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| Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. |
| Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2014/10/20 |
| revised |
2015/03/26 |
| accepted |
2015/05/13 |
| entrez |
2015/06/08 06:00 |
| pubmed |
2015/06/08 06:00 |
| medline |
2015/08/25 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Arloth J |
|
Arloth |
Janine |
J |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Bogdan R |
|
Bogdan |
Ryan |
R |
|
Department of Psychology, Washington University in St. Louis, St. Louis, MO 63130, USA. |
| Weber P |
|
Weber |
Peter |
P |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Frishman G |
|
Frishman |
Goar |
G |
|
Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany. |
| Menke A |
|
Menke |
Andreas |
A |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Wagner KV |
|
Wagner |
Klaus V |
KV |
|
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Balsevich G |
|
Balsevich |
Georgia |
G |
|
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Schmidt MV |
|
Schmidt |
Mathias V |
MV |
|
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Karbalai N |
|
Karbalai |
Nazanin |
N |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Czamara D |
|
Czamara |
Darina |
D |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Altmann A |
|
Altmann |
Andre |
A |
|
Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Palo Alto, CA 94304, USA. |
| Trümbach D |
|
Trümbach |
Dietrich |
D |
|
Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany. |
| Wurst W |
|
Wurst |
Wolfgang |
W |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany; Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany; Technische Universität München, c/o Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Developmental Genetics, Neuherberg 85764, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), Site Munich, Munich 80336, Germany. |
| Mehta D |
|
Mehta |
Divya |
D |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Uhr M |
|
Uhr |
Manfred |
M |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Klengel T |
|
Klengel |
Torsten |
T |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Erhardt A |
|
Erhardt |
Angelika |
A |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Carey CE |
|
Carey |
Caitlin E |
CE |
|
Department of Psychology, Washington University in St. Louis, St. Louis, MO 63130, USA. |
| Conley ED |
|
Conley |
Emily Drabant |
ED |
|
23andMe, Mountain View, CA 94043, USA. |
|
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (PGC) |
|
|
|
|
|
| Ruepp A |
|
Ruepp |
Andreas |
A |
|
Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany. |
| Müller-Myhsok B |
|
Müller-Myhsok |
Bertram |
B |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany. |
| Hariri AR |
|
Hariri |
Ahmad R |
AR |
|
Department of Psychology and Neuroscience, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA. |
| Binder EB |
|
Binder |
Elisabeth B |
EB |
|
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA. Electronic address: binder@psych.mpg.de. |
|
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium PGC |
|
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|
|
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| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Ripke |
Stephan |
S |
|
| Wray |
Naomi R |
NR |
|
| Lewis |
Cathryn M |
CM |
|
| Hamilton |
Steven P |
SP |
|
| Weissman |
Myrna M |
MM |
|
| Breen |
Gerome |
G |
|
| Byrne |
Enda M |
EM |
|
| Blackwood |
Douglas H R |
DH |
|
| Boomsma |
Dorret I |
DI |
|
| Cichon |
Sven |
S |
|
| Heath |
Andrew C |
AC |
|
| Holsboer |
Florian |
F |
|
| Lucae |
Susanne |
S |
|
| Madden |
Pamela A F |
PA |
|
| Martin |
Nicholas G |
NG |
|
| McGuffin |
Peter |
P |
|
| Muglia |
Pierandrea |
P |
|
| Noethen |
Markus M |
MM |
|
| Penninx |
Brenda P |
BP |
|
| Pergadia |
Michele L |
ML |
|
| Potash |
James B |
JB |
|
| Rietschel |
Marcella |
M |
|
| Lin |
Danyu |
D |
|
| Müller-Myhsok |
Bertram |
B |
|
| Shi |
Jianxin |
J |
|
| Steinberg |
Stacy |
S |
|
| Grabe |
Hans J |
HJ |
|
| Lichtenstein |
Paul |
P |
|
| Magnusson |
Patrik |
P |
|
| Perlis |
Roy H |
RH |
|
| Preisig |
Martin |
M |
|
| Smoller |
Jordan W |
JW |
|
| Stefansson |
Kari |
K |
|
| Uher |
Rudolf |
R |
|
| Kutalik |
Zoltan |
Z |
|
| Tansey |
Katherine E |
KE |
|
| Teumer |
Alexander |
A |
|
| Viktorin |
Alexander |
A |
|
| Barnes |
Michael R |
MR |
|
| Bettecken |
Thomas |
T |
|
| Binder |
Elisabeth B |
EB |
|
| Breuer |
René |
R |
|
| Castro |
Victor M |
VM |
|
| Churchill |
Susanne E |
SE |
|
| Coryell |
William H |
WH |
|
| Craddock |
Nick |
N |
|
| Craig |
Ian W |
IW |
|
| Czamara |
Darina |
D |
|
| De Geus |
Eco J |
EJ |
|
| Degenhardt |
Franziska |
F |
|
| Farmer |
Anne E |
AE |
|
| Fava |
Maurizio |
M |
|
| Frank |
Josef |
J |
|
| Gainer |
Vivian S |
VS |
|
| Gallagher |
Patience J |
PJ |
|
| Gordon |
Scott D |
SD |
|
| Goryachev |
Sergey |
S |
|
| Gross |
Magdalena |
M |
|
| Guipponi |
Michel |
M |
|
| Henders |
Anjali K |
AK |
|
| Herms |
Stefan |
S |
|
| Hickie |
Ian B |
IB |
|
| Hoefels |
Susanne |
S |
|
| Hoogendijk |
Witte |
W |
|
| Hottenga |
Jouke Jan |
JJ |
|
| Iosifescu |
Dan V |
DV |
|
| Ising |
Marcus |
M |
|
| Jones |
Ian |
I |
|
| Jones |
Lisa |
L |
|
| Jung-Ying |
Tzeng |
T |
|
| Knowles |
James A |
JA |
|
| Kohane |
Isaac S |
IS |
|
| Kohli |
Martin A |
MA |
|
| Korszun |
Ania |
A |
|
| Landen |
Mikael |
M |
|
| Lawson |
William B |
WB |
|
| Lewis |
Glyn |
G |
|
| MacIntyre |
Donald |
D |
|
| Maier |
Wolfgang |
W |
|
| Mattheisen |
Manuel |
M |
|
| McGrath |
Patrick J |
PJ |
|
| McIntosh |
Andrew |
A |
|
| McLean |
Alan |
A |
|
| Middeldorp |
Christel M |
CM |
|
| Middleton |
Lefkos |
L |
|
| Montgomery |
Grant M |
GM |
|
| Murphy |
Shawn N |
SN |
|
| Nauck |
Matthias |
M |
|
| Nolen |
Willem A |
WA |
|
| Nyholt |
Dale R |
DR |
|
| O'Donovan |
Michael |
M |
|
| Oskarsson |
Högni |
H |
|
| Pedersen |
Nancy |
N |
|
| Scheftner |
William A |
WA |
|
| Schulz |
Andrea |
A |
|
| Schulze |
Thomas G |
TG |
|
| Shyn |
Stanley I |
SI |
|
| Sigurdsson |
Engilbert |
E |
|
| Slager |
Susan L |
SL |
|
| Smit |
Johannes H |
JH |
|
| Stefansson |
Hreinn |
H |
|
| Steffens |
Michael |
M |
|
| Thorgeirsson |
Thorgeir |
T |
|
| Tozzi |
Federica |
F |
|
| Treutlein |
Jens |
J |
|
| Uhr |
Manfred |
M |
|
| van den Oord |
Edwin J C G |
EJ |
|
| Van Grootheest |
Gerard |
G |
|
| Völzke |
Henry |
H |
|
| Weilburg |
Jeffrey B |
JB |
|
| Willemsen |
Gonneke |
G |
|
| Zitman |
Frans G |
FG |
|
| Neale |
Benjamin |
B |
|
| Daly |
Mark |
M |
|
| Levinson |
Douglas F |
DF |
|
| Sullivan |
Patrick F |
PF |
|
|
| JOURNAL |
|
| VOLUME: 86 |
| ISSUE: 5 |
| TITLE: Neuron |
| ISOABBREVIATION: Neuron |
| YEAR: 2015 |
| MONTH: Jun |
| DAY: 3 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1097-4199 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Neuron |
| COUNTRY: United States |
| ISSNLINKING: 0896-6273 |
| NLMUNIQUEID: 8809320 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
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|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 104036 |
Wellcome Trust |
United Kingdom |
| R01 DA033369 |
NIDA NIH HHS |
United States |
| R01-DA031579 |
NIDA NIH HHS |
United States |
| R01-DA033369 |
NIDA NIH HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Animals |
|
| Brain |
physiology |
| Cohort Studies |
physiology |
| Forecasting |
physiology |
| Gene Regulatory Networks |
genetics |
| Genetic Variation |
genetics |
| Humans |
genetics |
| Male |
genetics |
| Mental Disorders |
genetics |
| Mice |
genetics |
| Mice, Inbred C57BL |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Risk Factors |
genetics |
| Stress, Psychological |
genetics |
| Transcriptome |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| PMC4490780 |
NLM |
|
|
