PMID- 22990943
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20211021
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 38
IP  - 3
DP  - 2013 Feb
TI  - Candidate genes expression profile associated with antidepressants response in 
      the GENDEP study: differentiating between baseline 'predictors' and longitudinal 
      'targets'.
PG  - 377-85
LID - 10.1038/npp.2012.191 [doi]
AB  - To improve the 'personalized-medicine' approach to the treatment of depression, 
      we need to identify biomarkers that, assessed before starting treatment, predict 
      future response to antidepressants ('predictors'), as well as biomarkers that are 
      targeted by antidepressants and change longitudinally during the treatment 
      ('targets'). In this study, we tested the leukocyte mRNA expression levels of 
      genes belonging to glucocorticoid receptor (GR) function (FKBP-4, FKBP-5, and 
      GR), inflammation (interleukin (IL)-1alpha, IL-1beta, IL-4, IL-6, IL-7, IL-8, IL-10, 
      macrophage inhibiting factor (MIF), and tumor necrosis factor (TNF)-alpha), and 
      neuroplasticity (brain-derived neurotrophic factor (BDNF), p11 and VGF), in 
      healthy controls (n=34) and depressed patients (n=74), before and after 8 weeks 
      of treatment with escitalopram or nortriptyline, as part of the Genome-based 
      Therapeutic Drugs for Depression study. Non-responders had higher baseline mRNA 
      levels of IL-1beta (+33%), MIF (+48%), and TNF-alpha (+39%). Antidepressants reduced the 
      levels of IL-1beta (-6%) and MIF (-24%), and increased the levels of GR (+5%) and 
      p11 (+8%), but these changes were not associated with treatment response. In 
      contrast, successful antidepressant response was associated with a reduction in 
      the levels of IL-6 (-9%) and of FKBP5 (-11%), and with an increase in the levels 
      of BDNF (+48%) and VGF (+20%)-that is, response was associated with changes in 
      genes that did not predict, at the baseline, the response. Our findings indicate 
      a dissociation between 'predictors' and 'targets' of antidepressant responders. 
      Indeed, while higher levels of proinflammatory cytokines predict lack of future 
      response to antidepressants, changes in inflammation associated with 
      antidepressant response are not reflected by all cytokines at the same time. In 
      contrast, modulation of the GR complex and of neuroplasticity is needed to 
      observe a therapeutic antidepressant effect.
FAU - Cattaneo, Annamaria
AU  - Cattaneo A
AD  - Department of Biomedical Sciences and Biotechnology, Genetic and Biology Section, 
      University of Brescia, Brescia, Italy.
FAU - Gennarelli, Massimo
AU  - Gennarelli M
FAU - Uher, Rudolf
AU  - Uher R
FAU - Breen, Gerome
AU  - Breen G
FAU - Farmer, Anne
AU  - Farmer A
FAU - Aitchison, Katherine J
AU  - Aitchison KJ
FAU - Craig, Ian W
AU  - Craig IW
FAU - Anacker, Christoph
AU  - Anacker C
FAU - Zunsztain, Patricia A
AU  - Zunsztain PA
FAU - McGuffin, Peter
AU  - McGuffin P
FAU - Pariante, Carmine M
AU  - Pariante CM
LA  - eng
GR  - MR/J002739/1/MRC_/Medical Research Council/United Kingdom
GR  - G108/603/MRC_/Medical Research Council/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120919
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Antidepressive Agents)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Macrophage Migration-Inhibitory Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.2.1 (MIF protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antidepressive Agents/*administration & dosage
MH  - Depressive Disorder/drug therapy/*genetics/metabolism
MH  - Drug Delivery Systems/*methods
MH  - Female
MH  - Genetic Association Studies/*methods
MH  - Genome-Wide Association Study/*methods
MH  - Humans
MH  - Interleukin-1beta/biosynthesis/genetics
MH  - Intramolecular Oxidoreductases/biosynthesis/genetics
MH  - Longitudinal Studies
MH  - Macrophage Migration-Inhibitory Factors/biosynthesis/genetics
MH  - Male
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Transcriptome/drug effects/*genetics
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/biosynthesis/genetics
PMC - PMC3547188
EDAT- 2012/09/20 06:00
MHDA- 2013/10/18 06:00
PMCR- 2013/02/01
CRDT- 2012/09/20 06:00
PHST- 2012/09/20 06:00 [entrez]
PHST- 2012/09/20 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
PHST- 2013/02/01 00:00 [pmc-release]
AID - npp2012191 [pii]
AID - 10.1038/npp.2012.191 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2013 Feb;38(3):377-85. doi: 10.1038/npp.2012.191. Epub 
      2012 Sep 19.