title: A variant of the neuronal amino acid transporter SLC6A15 is associated with ACTH and cortisol responses and cognitive performance in unipolar depression.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Germany. anna.schuhmacher@ukb.uni-bonn.de
authors.forename: Anna
authors.initials: A
authors.lastname: Schuhmacher
authors.forename: Leonhard
authors.initials: L
authors.lastname: Lennertz
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Susanne
authors.initials: S
authors.lastname: Höfels
authors.forename: Ute
authors.initials: U
authors.lastname: Pfeiffer
authors.forename: Vera
authors.initials: V
authors.lastname: Guttenthaler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Astrid
authors.initials: A
authors.lastname: Zobel
authors.forename: Rainald
authors.initials: R
authors.lastname: Mössner
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000378:metabolism; D000328:Adult; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D003071:Cognition / Q000502:physiology*; D003866:Depressive Disorder / Q000097:blood* / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D015415:Biomarkers; D009419:Nerve Tissue Proteins; C506212:SLC6A15 protein, human; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone