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Expression of glucocorticoid inducible genes is associated with reductions in cornu ammonis and dentate gyrus volumes in patients with major depressive disorder

Published online by Cambridge University Press:  25 November 2014

Thomas Frodl ,
Angela Carballedo ,
Eva-Maria Frey ,
Veronica O'Keane ,
Norbert Skokauskas ,
Derrek Morris ,
Michael Gill ,
Martina Mary Hughes ,
Andrew Harkin  and
Thomas Connor
Thomas Frodl*
Affiliation:
Trinity College Dublin University of Regensburg
Angela Carballedo
Affiliation:
Trinity College Dublin
Eva-Maria Frey
Affiliation:
University of Regensburg
Veronica O'Keane
Affiliation:
Trinity College Dublin
Norbert Skokauskas
Affiliation:
Trinity College Dublin Norwegian University of Science and Technology
Derrek Morris
Affiliation:
Trinity College Dublin
Michael Gill
Affiliation:
Trinity College Dublin
Martina Mary Hughes
Affiliation:
Trinity College Dublin
Andrew Harkin
Affiliation:
Trinity College Dublin
Thomas Connor
Affiliation:
Trinity College Dublin
*
Address correspondence and reprint requests to: Thomas Frodl, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland; E-mail: frodlt@tcd.ie.
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Abstract

Alterations of the glucocorticoid system and of hippocampal volumes have consistently been reported in patients with major depressive disorders (MDD). The aim of the present study was to investigate whether the messenger RNA (mRNA) expression of glucocorticoid inducible genes is associated with changes in the cornu ammonis (CA) and dentate gyrus subfields. Forty-three patients with MDD and 43 healthy controls were recruited and investigated with high resolution magnetic resonance imaging. Hippocampal subfields were measured using freesurfer. Measurement of whole blood mRNA expression of glucocorticoid inducible genes serum and glucocorticoid-regulated kinase 1 (SGK1), FK506 binding protein 5 (FKBP5), and glucocorticoid induced leucine zipper (GILZ) was performed. Patients with MDD had significantly smaller volumes of CA1, CA2/3, CA4/DG, and subiculum compared to healthy controls. In the regression analysis, the factor diagnosis had a significant moderating effect on the association of SGK1 and hippocampal volumes. Patients with low expression of SGK1 had significantly smaller CA2/3 and CA4/DG volumes compared to patients with high expression of SGK1 mRNA and to healthy controls with low/high expression of SGK1, respectively. Therefore, a lack of mRNA expression of glucocorticoid inducible genes in patients with MDD that seems to correspond to a blunted cortisol response is associated with smaller hippocampal CA and dentate gyrus volumes. SGK1 seems to be particularly relevant for stress-related mental disorders.

Type
Regular Articles
Information
Development and Psychopathology , Volume 26 , Special Issue 4pt2: Multilevel Developmental Perspectives Toward Understanding Internalizing Psychopathology: Current Research and Future Directions , November 2014 , pp. 1209 - 1217
Copyright
Copyright © Cambridge University Press 2014 

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