A variant of the neuronal amino acid transporter SLC6A15 is associated with ACTH and cortisol responses and cognitive performance in unipolar depression

作者：Schuhmacher Anna^*; Lennertz Leonhard; Wagner Michael; Hoefels Susanne; Pfeiffer Ute; Guttenthaler Vera; Maier Wolfgang; Zobel Astrid; Moessner Rainald

来源：International Journal of Neuropsychopharmacology, 2013, 16(1): 83-90.

DOI：10.1017/S1461145712000223

• Attention
• cognition
• cortisol
• depression
• Dex/CRH test
• HPA
• memory
• rs1545843
• SLC6A15

Major depressive disorder (MDD) is accompanied by both cognitive impairments and a hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system, resulting in an enhanced glucocorticoid secretion. Cortisol acts via mineralocorticoid and glucocorticoid receptors densely located in the hippocampus, a brain area that is important regarding cognitive functions and especially memory functions. Recently, a variant (rs1545843) affecting transcription of the human SLC6A15 gene has been associated with depression in a genome-wide association study. In an animal model, the neuronal amino acid transporter SLC6A15 was found to be decreased in stress-susceptible mice. Against the background of stress impacting on the activity of the HPA axis, we have investigated alterations of adrenocorticotropic hormone (ACTH) and cortisol secretion in the combined dexamethasone/corticotrophin-releasing hormone (Dex/CRH) test as well as memory and attention performance in a sample of 248 patients with unipolar depression and 172 healthy control subjects genotyped for rs1545843. MDD patients carrying the depression-associated AA genotype showed enhanced maximum and area under the curve ACTH and cortisol answers (p=0.03) as well as an impaired memory and impaired sustained attention performance (p=0.04) compared to carriers of at least one G allele. No effects of the SLC6A15 variant were found in the healthy control group. Our findings argue for a role of the SLC6A15 gene in ACTH and cortisol secretion during the Dex/CRH test and furthermore in the occurrence of cognitive impairments in unipolar depression.

• 出版日期2013-2