|Citation||Kohli MA, 2011 PubMed
|Full Info||Kohli MA, Lucae S, Saemann PG, Schmidt MV, Demirkan A, Hek K et al. The neuronal transporter gene SLC6A15 confers risk to major depression. Neuron 2011; 70(2): 252-265.
|Hypothesis or Background
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.
|Sample Information||sample of MD inpatients of a tertiary clinic in Munich, Germany, and matched controls devoid of any life-time psychiatric diagnoses (n = 353/366) recruited for the Munich, animal model|
|Method Keywords||genotyping; magnetic resonance imaging (MRI)
|Result||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.
|Conclusions||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.
Relationships reported by Kohli MA, 2011