Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis.
BACKGROUND
In depressed patients, alterations in the hypothalamo-pituitary-adrenocortical (HPA) system are the most consistent neurobiological finding. HPA axis activity and cytokines are intrinsically intertwined: inflammatory cytokines stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion, while, in turn, glucocorticoids suppress the synthesis of proinflammatory cytokines.


METHODS
We examined alterations in plasma levels of tumor necrosis factor-alpha (TNF-alpha), levels of its soluble receptors p55 (sTNF-R p55) and p75 (sTNF-R p75) as well as changes in the HPA system function using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 70 depressed inpatients without inflammation.


RESULTS
On admission, TNF-alpha levels were inversely associated with the ACTH response to the combined dex/CRH test. Changes in TNF-alpha, sTNF-R p55, and sTNF-R p75 plasma levels from admission to discharge were positively correlated with the dex/CRH test outcome at discharge. Subgroup analysis revealed that this association was restricted to those patients achieving remission. In this subgroup, TNF-alpha levels at discharge were also positively correlated with dex/CRH test response at discharge.


CONCLUSIONS
Our results suggest that elevated HPA axis activity in acute depression suppresses TNF-alpha system activity, while after remission, when HPA axis activity has normalized, the TNF-alpha system seems to gain influence on the HPA system.
Himmerich
Hubertus
H
Max Planck Institute of Psychiatry, Munich, Germany. himmerich@mpipsykl.mpg.de
Binder
Elisabeth B
EB
Künzel
Heike E
HE
Schuld
Andreas
A
Lucae
Susanne
S
Uhr
Manfred
M
Pollmächer
Thomas
T
Holsboer
Florian
F
Ising
Marcus
M
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D003907:Dexamethasone; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012008:Recurrence; D053319:Tumor Necrosis Factor Decoy Receptors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000502:physiology*
D000928:Antidepressive Agents; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone