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The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events
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Won, Eun Soo
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Korea Univ, Phamacogenet Res Ctr Psychotrop Drugs, Seoul 136705, South Korea
Korea Univ, Coll Med, Dept Psychiat, Seoul 136705, South Korea
Korea Univ, Coll Med, Anam Hosp, Dept Psychiat, Seoul 136705, South Korea Soonchunhyang Univ, Grad Sch, Dept Med Biosci, Puchon 420767, South Korea

Lee, Hwa-Young
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Soonchunhyang Univ, Coll Med, Dept Psychiat, Cheonan 330721, South Korea Soonchunhyang Univ, Grad Sch, Dept Med Biosci, Puchon 420767, South Korea

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Kim, Yong-Gu
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Korea Univ, Phamacogenet Res Ctr Psychotrop Drugs, Seoul 136705, South Korea
Korea Univ, Coll Med, Dept Psychiat, Seoul 136705, South Korea
Korea Univ, Coll Med, Anam Hosp, Dept Psychiat, Seoul 136705, South Korea Soonchunhyang Univ, Grad Sch, Dept Med Biosci, Puchon 420767, South Korea

Lee, Min-Soo
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Korea Univ, Phamacogenet Res Ctr Psychotrop Drugs, Seoul 136705, South Korea
Korea Univ, Coll Med, Dept Psychiat, Seoul 136705, South Korea
Korea Univ, Coll Med, Anam Hosp, Dept Psychiat, Seoul 136705, South Korea Soonchunhyang Univ, Grad Sch, Dept Med Biosci, Puchon 420767, South Korea
机构:
[1] Soonchunhyang Univ, Grad Sch, Dept Med Biosci, Puchon 420767, South Korea
[2] Korea Univ, Phamacogenet Res Ctr Psychotrop Drugs, Seoul 136705, South Korea
[3] Korea Univ, Coll Med, Dept Psychiat, Seoul 136705, South Korea
[4] Korea Univ, Coll Med, Anam Hosp, Dept Psychiat, Seoul 136705, South Korea
[5] Soonchunhyang Univ, Coll Med, Dept Psychiat, Cheonan 330721, South Korea
关键词:
Proopiomelanocortin;
Genetic polymorphism;
Life stress;
Treatment outcome;
Antidepressant;
Major depressive disorder;
CORTICOTROPIN-RELEASING HORMONE;
RECEPTOR GENE;
POPULATION;
HAPLOTYPE;
SEVERITY;
SYSTEM;
ACTH;
METAANALYSIS;
REPLICATION;
VARIANTS;
D O I:
10.1007/s00702-014-1333-9
中图分类号:
R74 [神经病学与精神病学];
学科分类号:
摘要:
Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is among the most consistent neuroendocrine abnormalities in major depressive disorder (MDD). The peptide adrenocorticotropin hormone (ACTH) mediates HPA axis function during stress and is encoded by the proopiomelanocortin (POMC) gene polycistronically. After screening 39 POMC polymorphisms, we evaluated the association of polymorphisms with susceptibility to MDD in 145 MDD patients and 193 normal subjects; in patients, we also evaluated the response to treatment with antidepressants. Additionally, we investigated the role of gene-environment interaction between POMC haplotypes and stressful life events (SLE) in the treatment response. Although genotypes and haplotypes were not significantly associated with the risk of MDD, non-remitters were more likely to carry haplotype 1 (ht1) and to have no ht2 than were remitters (corrected P = 0.010-0.035). Although observations were limited in patients without SLE, a significant haplotype-SLE interaction was observed (P = 0.020). Additionally, at 1, 2, and 8 weeks of treatment, the 21-item Hamilton Depression Rating scores of MDD subjects with POMC ht2 were significantly (P = 0.003-0.044) lower than those of patients with ht1 in subjects those did not experience SLE. MDD subjects possessing POMC ht2 achieved remission significantly (P = 0.013; survival analysis) faster than patients with ht1. This study suggests that POMC haplotypes, via an interaction with SLE, are associated with antidepressant treatment outcomes in MDD patients. Regarding SLE, haplotypes of the POMC gene could be useful markers for predicting the response to antidepressant treatment in MDD patients.
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页码:59 / 68
页数:10
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机构: COLL FRANCE, INSERM, U36, PARIS, FRANCE

Lenne, F
论文数: 0 引用数: 0
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机构: COLL FRANCE, INSERM, U36, PARIS, FRANCE

Auzan, C
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h-index: 0
机构: COLL FRANCE, INSERM, U36, PARIS, FRANCE

Jegou, S
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h-index: 0
机构: COLL FRANCE, INSERM, U36, PARIS, FRANCE

Rene, P
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机构: COLL FRANCE, INSERM, U36, PARIS, FRANCE

Vaudry, H
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h-index: 0
机构: COLL FRANCE, INSERM, U36, PARIS, FRANCE

Kuhn, JM
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h-index: 0
机构: COLL FRANCE, INSERM, U36, PARIS, FRANCE

Luton, JP
论文数: 0 引用数: 0
h-index: 0
机构: COLL FRANCE, INSERM, U36, PARIS, FRANCE

Clauser, E
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h-index: 0
机构: COLL FRANCE, INSERM, U36, PARIS, FRANCE

Bertagna, X
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机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Burcescu, Irina
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Wigg, Karen
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Kiss, Eniko
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Baji, Ildiko
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Gadoros, Julia
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Tamas, Zsuzsanna
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Kennedy, James L.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Vetro, Agnes
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Kovacs, Maria
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada

Barr, Cathy L.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Hlth Network, Toronto Westren Res Inst, Genet & Dev Div, Toronto, ON, Canada