Psychological Medicine

Original Articles

Regulation of mRNA expression encoding chaperone and co-chaperone proteins of the glucocorticoid receptor in peripheral blood: association with depressive symptoms during pregnancy

E. R. Katza1, Z. N. Stowea1a3, D. J. Newporta1, M. E. Kelleya2, T. W. Pacea1, J. F. Cubellsa1a4 and E. B. Bindera1a5 c1

a1 Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA

a2 Rollins School of Public Health, Department of Biostatistics and Bioinformatics Atlanta GA, USA

a3 Emory University School of Medicine, Department of Obstetrics and Gynecology, Atlanta, GA, USA

a4 Emory University School of Medicine, Department of Human Genetics, Atlanta, GA, USA

a5 Max Planck Institute of Psychiatry, Munich, Germany

Abstract

Background Major depressive disorder during pregnancy associates with potentially detrimental consequences for mother and child. The current study examined peripheral blood gene expression as a potential biomarker for prenatal depressive symptoms.

Method Maternal RNA from whole blood, plasma and the Beck Depression Inventory were collected longitudinally from preconception through the third trimester of pregnancy in 106 women with a lifetime history of mood or anxiety disorders. The expression of 16 genes in whole blood involved in glucorticoid receptor (GR) signaling was assessed using real-time polymerase chain reaction. In parallel, plasma concentrations of progesterone, estradiol and cortisol were measured. Finally, we assessed ex vivo GR sensitivity in peripheral blood cells from a subset of 29 women.

Results mRNA expression of a number of GR-complex regulating genes was up-regulated over pregnancy. Women with depressive symptoms showed significantly smaller increases in mRNA expression of four of these genes – FKBP5, BAG1, NCOA1 and PPID. Ex vivo stimulation assays showed that GR sensitivity diminished with progression of pregnancy and increasing maternal depressive symptoms. Plasma concentrations of gonadal steroids and cortisol did not differ over pregnancy between women with and without clinically relevant depressive symptoms.

Conclusions The presence of prenatal depressive symptoms appears to be associated with altered regulation of GR sensitivity. Peripheral expression of GR co-chaperone genes may serve as a biomarker for risk of developing depressive symptoms during pregnancy. The presence of such biomarkers, if confirmed, could be utilized in treatment planning for women with a psychiatric history.

(Received February 15 2011)

(Revised August 31 2011)

(Accepted September 05 2011)

(Online publication October 14 2011)

Correspondence

c1 Address for correspondence: E. B. Binder, MD PhD, Max-Planck Institute of Psychiatry, Kraepelinstr. 2–10, 80804 Munich, Germany. (Email: binder@mpipsykl.mpg.de)

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