The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression

MA Kohli; S Lucae; PG Saemann; MV Schmidt; Ayse Demirkan; Karin Hek; D Czamara; M Alexander; D Salyakina; S Ripke; D Hoehn; M Specht; A Menke; J Hennings; A Heck; C Wolf; M Ising; S Schreiber; M Czisch; MB Muller; M Uhr; T Bettecken; A Becker; J Schramm; M Rietschel; W Maier; B Bradley; KJ Ressler; MM Nothen; S Cichon; IW Craig; G Breen; CM Lewis; Bert Hofman; Henning Tiemeier; Cornelia Duijn; F Holsboer; B Muller-Myhsok; EB Binder

doi:10.1016/j.neuron.2011.04.005

The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression

MA Kohli, S Lucae, PG Saemann, MV Schmidt, Ayse Demirkan, Karin Hek, D Czamara, M Alexander, D Salyakina, S Ripke, D Hoehn, M Specht, A Menke, J Hennings, A Heck, C Wolf, M Ising, S Schreiber, M Czisch, MB MullerM Uhr, T Bettecken, A Becker, J Schramm, M Rietschel, W Maier, B Bradley, KJ Ressler, MM Nothen, S Cichon, IW Craig, G Breen, CM Lewis, Bert Hofman, Henning Tiemeier, Cornelia Duijn, F Holsboer, B Muller-Myhsok, EB Binder

Research output: Contribution to journal › Article › Academic › peer-review

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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 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.

Original language	Undefined/Unknown
Pages (from-to)	252-265
Number of pages	14
Journal	Neuron
Volume	70
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2011.04.005
Publication status	Published - 2011

Research programs

EMC NIHES-01-64-01
EMC NIHES-01-64-02
EMC OR-01-58-01

Access to Document

10.1016/j.neuron.2011.04.005

http://hdl.handle.net/1765/26434

Cite this

Kohli, MA., Lucae, S., Saemann, PG., Schmidt, MV., Demirkan, A., Hek, K., Czamara, D., Alexander, M., Salyakina, D., Ripke, S., Hoehn, D., Specht, M., Menke, A., Hennings, J., Heck, A., Wolf, C., Ising, M., Schreiber, S., Czisch, M., ... Binder, EB. (2011). The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression. Neuron, 70(2), 252-265. https://doi.org/10.1016/j.neuron.2011.04.005

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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 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.",

author = "MA Kohli and S Lucae and PG Saemann and MV Schmidt and Ayse Demirkan and Karin Hek and D Czamara and M Alexander and D Salyakina and S Ripke and D Hoehn and M Specht and A Menke and J Hennings and A Heck and C Wolf and M Ising and S Schreiber and M Czisch and MB Muller and M Uhr and T Bettecken and A Becker and J Schramm and M Rietschel and W Maier and B Bradley and KJ Ressler and MM Nothen and S Cichon and IW Craig and G Breen and CM Lewis and Bert Hofman and Henning Tiemeier and Cornelia Duijn and F Holsboer and B Muller-Myhsok and EB Binder",

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doi = "10.1016/j.neuron.2011.04.005",

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Kohli, MA, Lucae, S, Saemann, PG, Schmidt, MV, Demirkan, A, Hek, K, Czamara, D, Alexander, M, Salyakina, D, Ripke, S, Hoehn, D, Specht, M, Menke, A, Hennings, J, Heck, A, Wolf, C, Ising, M, Schreiber, S, Czisch, M, Muller, MB, Uhr, M, Bettecken, T, Becker, A, Schramm, J, Rietschel, M, Maier, W, Bradley, B, Ressler, KJ, Nothen, MM, Cichon, S, Craig, IW, Breen, G, Lewis, CM, Hofman, B, Tiemeier, H, Duijn, C, Holsboer, F, Muller-Myhsok, B & Binder, EB 2011, 'The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression', Neuron, vol. 70, no. 2, pp. 252-265. https://doi.org/10.1016/j.neuron.2011.04.005

TY - JOUR

T1 - The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression

AU - Kohli, MA

AU - Lucae, S

AU - Saemann, PG

AU - Schmidt, MV

AU - Demirkan, Ayse

AU - Hek, Karin

AU - Czamara, D

AU - Alexander, M

AU - Salyakina, D

AU - Ripke, S

AU - Hoehn, D

AU - Specht, M

AU - Menke, A

AU - Hennings, J

AU - Heck, A

AU - Wolf, C

AU - Ising, M

AU - Schreiber, S

AU - Czisch, M

AU - Muller, MB

AU - Uhr, M

AU - Bettecken, T

AU - Becker, A

AU - Schramm, J

AU - Rietschel, M

AU - Maier, W

AU - Bradley, B

AU - Ressler, KJ

AU - Nothen, MM

AU - Cichon, S

AU - Craig, IW

AU - Breen, G

AU - Lewis, CM

AU - Hofman, Bert

AU - Tiemeier, Henning

AU - Duijn, Cornelia

AU - Holsboer, F

AU - Muller-Myhsok, B

AU - Binder, EB

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1016/j.neuron.2011.04.005

DO - 10.1016/j.neuron.2011.04.005

M3 - Article

C2 - 21521612

SN - 0896-6273

VL - 70

SP - 252

EP - 265

JO - Neuron

JF - Neuron

IS - 2

ER -