Reduced peripheral expression of the glucocorticoid receptor α isoform in individuals with posttraumatic stress disorder: a cumulative effect of trauma burden.
BACKGROUND
Posttraumatic stress disorder (PTSD) is a serious psychiatric condition that was found to be associated with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis and changes in glucocorticoid (GC) responsiveness. The physiological actions of GCs are primarily mediated through GC receptors (GR) of which isoforms with different biological activities exist. This study aimed to investigate whether trauma-experience and/or PTSD are associated with altered expression of GR splice variants.


METHODS
GRα and GRβ mRNA expression levels were determined by real-time quantitative PCR in whole blood samples of individuals with chronic and severe forms of PTSD (n = 42) as well as in ethnically matched reference subjects (non-PTSD, n = 35).


RESULTS
Individuals suffering from PTSD exhibited significantly lower expression of the predominant and functionally active GRα isoform compared to non-PTSD subjects. This effect remained significant when accounting for gender, smoking, psychotropic medication or comorbid depression. Moreover, the GRα expression level was significantly negatively correlated with the number of traumatic event types experienced, both in the whole sample and within the PTSD patient group. Expression of the less abundant and non-ligand binding GRβ isoform was comparable between patient and reference groups.


CONCLUSIONS
Reduced expression of the functionally active GRα isoform in peripheral blood cells of individuals with PTSD seems to be a cumulative effect of trauma burden rather than a specific feature of PTSD since non-PTSD subjects with high trauma load showed an intermediate phenotype between PTSD patients and individuals with no or few traumatic experiences.
Clinical and Biological Psychology, University of Ulm, Ulm, Germany.
Hannah
H
Gola
Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Andrea
A
Engler
Clinical Psychology and Neuropsychology, University of Konstanz, Konstanz, Germany.
Julia
J
Morath
Clinical Psychology and Neuropsychology, University of Konstanz, Konstanz, Germany.
Hannah
H
Adenauer
Clinical Psychology and Neuropsychology, University of Konstanz, Konstanz, Germany.
Thomas
T
Elbert
Clinical and Biological Psychology, University of Ulm, Ulm, Germany.
Iris-Tatjana
IT
Kolassa
Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Harald
H
Engler
D000293:Adolescent; D000328:Adult; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005938:Glucocorticoids / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*; D014947:Wounds and Injuries / Q000235:genetics; D055815:Young Adult
D005938:Glucocorticoids; D020033:Protein Isoforms; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta