The International Journal of Neuropsychopharmacology

Table of Contents - February 2013 - Volume 16, Issue 01  

Research Article

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

Anna Schuhmachera1 c1 *, Leonhard Lennertza1 *, Michael Wagnera1, Susanne Höfelsa1, Ute Pfeiffera1, Vera Guttenthalera1, Wolfgang Maiera1, Astrid Zobela1 * and Rainald Mössnera1 *

a1 Department of Psychiatry and Psychotherapy, University of Bonn, Germany

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.

(Received September 27 2011)

(Reviewed November 26 2011)

(Revised February 02 2012)

(Accepted February 17 2012)

(Online publication April 04 2012)

Key words

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

Correspondence:

c1 Address for correspondence: Dr A. Schuhmacher, Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany. Tel.: +49 228 287 15717 Fax: +49 228 287 16097 Email: anna.schuhmacher@ukb.uni-bonn.de

Footnotes

*  These authors contributed equally to this work.

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