The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression

被引：170

作者：

Kohli, Martin A. ^{[1
]}

Lucae, Susanne ^{[1
]}

Saemann, Philipp G. ^{[1
]}

Schmidt, Mathias V. ^{[1
]}

Demirkan, Ayse ^{[2
]}

Hek, Karin ^{[2
]}

Czamara, Darina ^{[1
]}

Alexander, Michael ^{[3
]}

Salyakina, Daria ^{[1
]}

Ripke, Stephan ^{[1
]}

Hoehn, David ^{[1
]}

Specht, Michael ^{[1
]}

Menke, Andreas ^{[1
]}

Hennings, Johannes ^{[1
]}

Heck, Angela ^{[1
]}

Wolf, Christiane ^{[1
]}

Ising, Marcus ^{[1
]}

Schreiber, Stefan ^{[4
]}

Czisch, Michael ^{[1
]}

Mueller, Marianne B. ^{[1
]}

Uhr, Manfred ^{[1
]}

Bettecken, Thomas ^{[1
]}

Becker, Albert ^{[1
,5
]}

Schramm, Johannes ^{[6
]}

Rietschel, Marcella ^{[7
]}

Maier, Wolfgang ^{[8
]}

Bradley, Bekh ^{[9
,10
]}

Ressler, Kerry J. ^{[9
,11
,13
]}

Noethen, Markus M. ^{[12
]}

Cichon, Sven ^{[3
,14
]}

Craig, Ian W. ^{[15
]}

Breen, Gerome ^{[15
]}

Lewis, Cathryn M. ^{[15
]}

Hofman, Albert ^{[2
]}

Tiemeier, Henning ^{[2
]}

van Duijn, Cornelia M. ^{[2
]}

Holsboer, Florian ^{[1
]}

Mueller-Myhsok, Bertram ^{[1
]}

Binder, Elisabeth B. ^{[1
]}

机构：

[1] Max Planck Inst Psychiat, D-80804 Munich, Germany

[2] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-300 CA Rotterdam, Netherlands

[3] Univ Bonn, Dept Genom, Life & Brain Ctr, Inst Human Genet, D-53127 Bonn, Germany

[4] Univ Kiel, Dept Gen Internal Med, D-24105 Kiel, Germany

[5] Univ Clin Bonn, Inst Neuropathol, D-53127 Bonn, Germany

[6] Univ Clin Bonn, Dept Neurosurg, D-53127 Bonn, Germany

[7] Heidelberg Univ, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68159 Mannheim, Germany

[8] Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany

[9] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA

[10] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[11] Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA

[12] Univ Bonn, Inst Human Genet, D-53115 Bonn, Germany

[13] Atlanta VA Med Ctr, Atlanta, GA 30033 USA

[14] Forschungszentrum Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany

[15] Kings Coll London, Inst Psychiat, London SE5 8AF, England

来源：

NEURON | 2011年 / 70卷 / 02期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; CHRONIC SOCIAL STRESS; HIPPOCAMPAL VOLUME; HOSPITAL ANXIETY; V7-3; SLC6A15; DISORDER; SYMPTOMS; NEUROENDOCRINE; POLYMORPHISMS; MECHANISMS;

D O I：

10.1016/j.neuron.2011.04.005

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Major depression (MD) is one of the most prevalent psychiatric disorders and a leading cause of loss in work productivity. A combination of genetic and environmental risk factors probably contributes to MD. We present data from a genome-wide association study revealing a neuron-specific neutral amino acid transporter (SLC6A15) as a susceptibility gene for MD. Risk allele carrier status in humans and chronic stress in mice were associated with a down-regulation of the expression of this gene in the hippocampus, a brain region implicated in the pathophysiology of MD. The same polymorphisms also showed associations with alterations in hippocampal volume and neuronal integrity. Thus, decreased SLC6A15 expression, due to genetic or environmental factors, might alter neuronal circuits related to the susceptibility for MD. Our convergent data from human genetics, expression studies, brain imaging, and animal models suggest a pathophysiological mechanism for MD that may be accessible to drug targeting.

引用

页码：252 / 265

页数：14

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