PMID- 23012888
OWN - NLM
STAT- MEDLINE
DCOM- 20121210
LR  - 20131121
IS  - 1340-2544 (Print)
IS  - 1340-2544 (Linking)
VI  - 32
IP  - 4
DP  - 2012 Aug
TI  - [The hypothalamic-pituitary-adrenal axis and depressive disorder: recent 
      progress].
PG  - 203-9
AB  - Depression is a stress-induced disorder and there is compelling evidence for the 
      involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in the 
      disease. Chronic hyperactivity of the HPA axis and resultant excessive 
      glucocorticoid (hypercortisolism) may be causal to depression. We demonstrated 
      that the dexamethasone (DEX)/CRH test is a sensitive state-dependent marker to 
      monitor HPA axis abnormalities. Restoration from HPA axis abnormalities occurs 
      with clinical responses to treatment. Brain-derived neurotrophic factor (BDNF) 
      has also been implicated in depression. We found that glucocorticoid (DEX) 
      suppresses BDNF-induced dendrite outgrowth and synaptic formation via blocking 
      the MAPK pathway in early-developing cultured hippocampal neurons. Furthermore, 
      we demonstrated that glucocorticoid receptor (GR) and TrkB (a specific receptor 
      of BDNF) interact and that DEX acutely suppresses BDNF-induced glutamate release 
      by affecting the PLC-gamma pathway in cultured cortical neurons, indicating a 
      mechanism underlying the effect of excessive glucocorticoid on BDNF function and 
      resultant damage in cortical neurons. In a macroscopic view using magnetic 
      resonance imaging (MRI), we found that individuals with hypercortisolism detected 
      by the DEX/CRH test demonstrated volume loss in gray matter and reduced neural 
      network assessed with diffusion tensor imaging in several brain regions. Finally, 
      we observed that individuals with hypocortisolism detected by the DEX/CRH test 
      tend to present more distress symptoms, maladaptive coping styles, and 
      schizotypal personality traits than their counterparts, which points to the 
      important role of hypocortisolism as well as hypercortisolism in depression 
      spectrum disorders.
FAU - Kunugi, Hiroshi
AU  - Kunugi H
AD  - Department of Mental Disorder Research, National Institute of Neuroscience, 
      National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 
      187-8502 Japan. hkunugi@ncnp.go.jp
FAU - Hori, Hiroaki
AU  - Hori H
FAU - Numakawa, Tadahiro
AU  - Numakawa T
FAU - Ota, Miho
AU  - Ota M
LA  - jpn
PT  - English Abstract
PT  - Journal Article
PT  - Review
PL  - Japan
TA  - Nihon Shinkei Seishin Yakurigaku Zasshi
JT  - Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology
JID - 9509023
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glucocorticoids)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Corticotropin-Releasing Hormone/*metabolism
MH  - Depression/diagnosis/*drug therapy
MH  - Dexamethasone/*therapeutic use
MH  - Glucocorticoids/*metabolism
MH  - Humans
MH  - *Pituitary-Adrenal System/drug effects/metabolism/physiopathology
EDAT- 2012/09/28 06:00
MHDA- 2012/12/12 06:00
CRDT- 2012/09/28 06:00
PHST- 2012/09/28 06:00 [entrez]
PHST- 2012/09/28 06:00 [pubmed]
PHST- 2012/12/12 06:00 [medline]
PST - ppublish
SO  - Nihon Shinkei Seishin Yakurigaku Zasshi. 2012 Aug;32(4):203-9.