The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression

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• 作者：Martin  ; A. Kohli¹ ; ¹⁶ ; ^{mkohli@med.miami.edu"" rel=""nofollow} ; Susanne Lucae¹ ; ¹⁶ ; Philipp  ; G. Saemann¹ ; Mathias  ; V. Schmidt¹ ; Ayse Demirkan² ; Karin Hek² ; Darina Czamara¹ ; Michael Alexander³ ; Daria Salyakina¹ ; Stephan Ripke¹ ; David Hoehn¹ ; Michael Specht¹ ; Andreas Menke¹ ; Johannes Hennings¹ ; Angela Heck¹ ; Christiane Wolf¹ ; Marcus Ising¹ ; Stefan Schreiber⁴ ; Michael Czisch¹ ; Marianne  ; B. M&#xfc ; ller¹ ; Manfred Uhr¹ ; Thomas Bettecken¹ ; Albert Becker⁵ ; Johannes Schramm⁶ ; Marcella Rietschel⁷ ; Wolfgang Maier⁸ ; Bekh Bradley⁹ ; ¹⁰ ; Kerry  ; J. Ressler⁹ ; ¹¹ ; ¹² ; Markus  ; M. Nö ; then¹³ ; Sven Cichon³ ; ¹⁴ ; Ian  ; W. Craig¹⁵ ; Gerome Breen¹⁵ ; Cathryn  ; M. Lewis¹⁵ ; Albert Hofman² ; Henning Tiemeier² ; Cornelia  ; M. van  ; Duijn² ; Florian Holsboer¹ ; Bertram M&#xfc ; ller-Myhsok¹ ; ¹⁷ ; Elisabeth  ; B. Binder¹ ; ⁹ ; ¹⁷ ; ^{binder@mpipsykl.mpg.de"" rel=""nofollow}
• 刊名：Neuron
• 出版年：2011
• 出版时间：28 April 2011
• 年：2011
• 卷：70
• 期：2
• 页码：252-265
• 全文大小：983 K

文摘

Summary

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 downregulation 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.