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rdf:type |
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lifeskim:mentions |
umls-concept:C0003289,
umls-concept:C0011581,
umls-concept:C0034897,
umls-concept:C0087111,
umls-concept:C0205217,
umls-concept:C0332281,
umls-concept:C0439831,
umls-concept:C0871261,
umls-concept:C1414627,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1882417,
umls-concept:C2911692
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pubmed:issue |
12
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pubmed:dateCreated |
2004-11-26
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pubmed:abstractText |
The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1061-4036
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pubmed:author |
pubmed-author:BaghaiThomasT,
pubmed-author:BetteckenThomasT,
pubmed-author:BinderElisabeth BEB,
pubmed-author:BondyBrigittaB,
pubmed-author:BrücklTanjaT,
pubmed-author:BrunnerJürgenJ,
pubmed-author:DabitzHeikeH,
pubmed-author:DeimlTobiasT,
pubmed-author:FuchsBrigitteB,
pubmed-author:HolsboerFlorianF,
pubmed-author:IsingMarcusM,
pubmed-author:KöhnleinOliverO,
pubmed-author:KünzelHeike EHE,
pubmed-author:KernNikolaN,
pubmed-author:KohliMartin AMA,
pubmed-author:LõhmussaarElinE,
pubmed-author:LichtnerPeterP,
pubmed-author:LiebRoselindR,
pubmed-author:LucaeSusanneS,
pubmed-author:MüllerNinaN,
pubmed-author:MajerMatthiasM,
pubmed-author:MeitingerThomasT,
pubmed-author:MesserThomasT,
pubmed-author:ModellSieglindeS,
pubmed-author:MuellerJakob CJC,
pubmed-author:Muller-MyhsokBertramB,
pubmed-author:NickelThomasT,
pubmed-author:PützBennoB,
pubmed-author:PapiolSergiS,
pubmed-author:PfennigAndreaA,
pubmed-author:PfisterHildegardH,
pubmed-author:ReinTheoT,
pubmed-author:RupprechtRainerR,
pubmed-author:SalyakinaDariaD,
pubmed-author:SeamanShaunS,
pubmed-author:StromTim MTM,
pubmed-author:UhrManfredM,
pubmed-author:WochnikGabriele MGM,
pubmed-author:ZillPeterP
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pubmed:issnType |
Print
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1319-25
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15565110-Adult,
pubmed-meshheading:15565110-Analysis of Variance,
pubmed-meshheading:15565110-Antidepressive Agents,
pubmed-meshheading:15565110-Blotting, Western,
pubmed-meshheading:15565110-Corticotropin-Releasing Hormone,
pubmed-meshheading:15565110-Depression,
pubmed-meshheading:15565110-Fluorescence,
pubmed-meshheading:15565110-Gene Frequency,
pubmed-meshheading:15565110-Genotype,
pubmed-meshheading:15565110-Germany,
pubmed-meshheading:15565110-HSP90 Heat-Shock Proteins,
pubmed-meshheading:15565110-Humans,
pubmed-meshheading:15565110-Hypothalamo-Hypophyseal System,
pubmed-meshheading:15565110-Lymphocytes,
pubmed-meshheading:15565110-Neurophysins,
pubmed-meshheading:15565110-Pituitary-Adrenal System,
pubmed-meshheading:15565110-Polymorphism, Single Nucleotide,
pubmed-meshheading:15565110-Protein Precursors,
pubmed-meshheading:15565110-Receptors, Glucocorticoid,
pubmed-meshheading:15565110-Regression Analysis,
pubmed-meshheading:15565110-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15565110-Vasopressins
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pubmed:year |
2004
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pubmed:articleTitle |
Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.
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