Lymphocyte glucocorticoid receptor resistance and depressive symptoms severity: a preliminary report.
OBJECTIVE
Assessment of the temporal interrelationship of neuropsychiatric parameters requires technologies allowing frequent biological measurements. We propose glucocorticoid receptor (GR) function of lymphocytes to assess the temporal relationship between glucocorticoid resistance and the course of major depressive disorder.


METHODS
Dexamethasone suppression of lymphocyte proliferation was in vitro assessed via 5-bromo-2' deoxyuridine (BrdU) incorporation in DNA. Optimal conditions were determined using blood of healthy volunteers. Thereafter the relation between depression severity (Hamilton Depression Rating Scale, HDRS, scores), lymphocyte proliferation and morning cortisol levels in blood was studied in thirteen depressed patients, mostly with a history of treatment resistance.


RESULTS
Recovery from depression was not directly associated with changes in lymphocyte glucocorticoid resistance. However, a negative correlation was observed between HDRS and BrdU incorporation and a positive correlation between morning cortisol and BrdU incorporation. No significant correlation was found between cortisol and HDRS. Regression analyses showed that HDRS was related to both suppression of BrdU incorporation (beta -0.508, p<0.001) and cortisol levels (beta 0.364, p=0.001) in a highly significant model (F2,60=14,244, p<0.001) Except for one case, such relation could not be found within patients.


CONCLUSIONS
Our preliminary results suggest a mutual relation between lymphocyte GR function, morning cortisol levels and MDD symptom severity. A direct relation between glucocorticoids resistance and recovery may not exist, but glucocorticoid resistance might attenuate or prevent recovery. It is clear that additional studies using larger and more homogenous groups of MDD patients are required to support our findings.
Tanke
M A C
MA
University Center of Psychiatry, University Medical Center of Groningen, University of Groningen, The Netherlands.
Bosker
F J
FJ
Gladkevich
A V
AV
Medema
H M
HM
den Boer
J A
JA
Korf
J
J
D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003863:Depression / Q000473:pathology*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D012044:Regression Analysis
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D001973:Bromodeoxyuridine