title: The neuronal transporter gene SLC6A15 confers risk to major depression.
abstract: 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.
authors.affiliation: Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Kohli
authors.forename: Susanne
authors.initials: S
authors.lastname: Lucae
authors.forename: Philipp G
authors.initials: PG
authors.lastname: Saemann
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
authors.forename: Ayse
authors.initials: A
authors.lastname: Demirkan
authors.forename: Karin
authors.initials: K
authors.lastname: Hek
authors.forename: Darina
authors.initials: D
authors.lastname: Czamara
authors.forename: Michael
authors.initials: M
authors.lastname: Alexander
authors.forename: Daria
authors.initials: D
authors.lastname: Salyakina
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.forename: David
authors.initials: D
authors.lastname: Hoehn
authors.forename: Michael
authors.initials: M
authors.lastname: Specht
authors.forename: Andreas
authors.initials: A
authors.lastname: Menke
authors.forename: Johannes
authors.initials: J
authors.lastname: Hennings
authors.forename: Angela
authors.initials: A
authors.lastname: Heck
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolf
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Michael
authors.initials: M
authors.lastname: Czisch
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Müller
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Thomas
authors.initials: T
authors.lastname: Bettecken
authors.forename: Albert
authors.initials: A
authors.lastname: Becker
authors.forename: Johannes
authors.initials: J
authors.lastname: Schramm
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Bekh
authors.initials: B
authors.lastname: Bradley
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Ian W
authors.initials: IW
authors.lastname: Craig
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
mesh_terms: D000328:Adult; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D015201:Meta-Analysis as Topic; D051379:Mice; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology; D014316:Tritium; D006113:United Kingdom
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C506212:SLC6A15 protein, human; D014316:Tritium; D001224:Aspartic Acid; C000179:N-acetylaspartate