Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.
Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes. Using a previously reported definition of HPA-axis responsive versus non-responsive phenotypes, we identified for the first time two clinically and biologically distinct HPA-axis reactivity subgroups of PTSD. One subgroup ("non-responders") showed a blunted HPA-axis response and distinct clinical and biological characteristics such as a higher prevalence of trauma-related dissociative symptoms and of combined AT and ELT as well as alterations in the expression kinetics of the genes encoding for the mineralocorticoid receptor (MR) and for FK506 binding protein 51 (FKBP51). Interestingly, this non-responder subgroup largely drove the relatively diminished HPA axis response of the total cohort of PTSD patients. These findings are limited by the facts that the majority of patients was medicated, by the lack of traumatized controls and by the relatively small sample size. The here for the first time identified and characterized HPA-axis reactivity endophenotypes offer an explanation for the inconsistent reports on HPA-axis function in PTSD and, moreover, suggest that most likely other factors than HPA-axis reactivity play a decisive role in determination of PTSD core symptom severity.
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Monika
M
Zaba
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Thomas
T
Kirmeier
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Irina A
IA
Ionescu
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Bastian
B
Wollweber
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Dominik R
DR
Buell
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Dominique J
DJ
Gall-Kleebach
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Christine F
CF
Schubert
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Bozidar
B
Novak
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Christine
C
Huber
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Katharina
K
Köhler
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Florian
F
Holsboer
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Benno
B
Pütz
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Bertram
B
Müller-Myhsok
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Nina
N
Höhne
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Manfred
M
Uhr
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Marcus
M
Ising
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany.
Leonie
L
Herrmann
Max Planck Institute of Psychiatry, Clinical Department, Kraepelinstrasse 10, 80804 München, Germany. Electronic address: uschmidt@mpipsykl.mpg.de.
Ulrike
U
Schmidt
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000069586:Adult Survivors of Child Adverse Events; D016022:Case-Control Studies; D015331:Cohort Studies; D058068:Endophenotypes; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D059467:Transcriptome; D000099159:Tacrolimus Binding Protein 5
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C497713:NR3C1 protein, human; C561839:NR3C2 protein, human; C403485:tacrolimus binding protein 4
FKBP5; Gene expression; PTSD; PTSD subtypes; Posttraumatic stress disorder; Stress reactivity; Trier Social Stress Test