PMID- 23570888
OWN - NLM
STAT- MEDLINE
DCOM- 20141009
LR  - 20240318
IS  - 1545-7214 (Electronic)
IS  - 1064-7481 (Print)
IS  - 1064-7481 (Linking)
VI  - 21
IP  - 5
DP  - 2013 May
TI  - Anticipated brain molecular aging in major depression.
PG  - 450-60
LID - S1064-7481(13)00045-6 [pii]
LID - 10.1016/j.jagp.2013.01.040 [doi]
AB  - OBJECTIVES: Brain molecular aging, the pervasive and consistent transcriptome 
      changes associated with normal brain aging, appears to overlap with disease 
      pathways and may be anticipated in neurodegenerative and neuropsychiatric 
      diseases, including major depressive disorder (MDD). Here, we characterize the 
      global interaction of MDD-related gene changes with age, starting from our 
      previous report of downregulated brain-derived neurotrophic factor (BDNF) and 
      BDNF-dependent genes in the amygdala of women with MDD. METHODS: A large-scale 
      gene expression data set in the amygdala from a postmortem cohort of 21 women 
      with MDD and 21 age-matched controls (age range: 16-74 years) was analyzed for 
      correlations of gene transcript changes with age, in the presence or absence of a 
      diagnosis of MDD. RESULTS: 1) The age-related decrease in BDNF transcripts 
      observed in control subjects corresponds with further age-related decreases in 
      BDNF and BDNF-dependent gene expression in MDD subjects; 2) most MDD-related 
      genes are frequently age-regulated in both MDD and control subjects; 3) the 
      effects of MDD and age are positively correlated; 4) most genes that are 
      age-dependent in control subjects display greater age effects in MDD subjects; 
      and 5) the increased prevalence of age effects in MDD corresponds to similar 
      trends in controls, rather than representing de novo age effects. CONCLUSIONS: 
      MDD strongly associates with robust and anticipated gene expression changes that 
      occur during normal aging of the brain, suggesting that an older molecular age of 
      the brain represents an early biological event and/or a marker of risk for 
      subsequent onset of MDD symptoms.
CI  - Copyright (c) 2013 American Association for Geriatric Psychiatry. Published by 
      Elsevier Inc. All rights reserved.
FAU - Douillard-Guilloux, Gaelle
AU  - Douillard-Guilloux G
AD  - Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15219, USA.
FAU - Guilloux, Jean-Philippe
AU  - Guilloux JP
FAU - Lewis, David A
AU  - Lewis DA
FAU - Sibille, Etienne
AU  - Sibille E
LA  - eng
GR  - R01 MH093723/MH/NIMH NIH HHS/United States
GR  - R01 MH077159/MH/NIMH NIH HHS/United States
GR  - P50 MH084053/MH/NIMH NIH HHS/United States
GR  - R37 MH043784/MH/NIMH NIH HHS/United States
GR  - MH093723/MH/NIMH NIH HHS/United States
GR  - R01 MH043784/MH/NIMH NIH HHS/United States
GR  - K02 MH084060/MH/NIMH NIH HHS/United States
GR  - MH043784/MH/NIMH NIH HHS/United States
GR  - MH084053/MH/NIMH NIH HHS/United States
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - MH084060/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130206
PL  - England
TA  - Am J Geriatr Psychiatry
JT  - The American journal of geriatric psychiatry : official journal of the American 
      Association for Geriatric Psychiatry
JID - 9309609
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aging/*genetics/*psychology
MH  - Amygdala/*metabolism
MH  - Biomarkers/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Case-Control Studies
MH  - Depressive Disorder, Major/*genetics/*metabolism/psychology
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Humans
MH  - Middle Aged
PMC - PMC3615087
MID - NIHMS397143
COIS- Conflict of interest David A. Lewis currently receives investigator-initiated 
      research support from Bristol-Myers Squibb, Curridium Ltd and Pfizer and in 
      2009-2011 served as a consultant in the areas of target identification and 
      validation and new compound development to BioLine RX, Bristol-Myers Squibb, 
      Merck and SK Life Science. The other authors declare no conflicts of interest.
EDAT- 2013/04/11 06:00
MHDA- 2014/10/10 06:00
PMCR- 2014/05/01
CRDT- 2013/04/11 06:00
PHST- 2012/01/23 00:00 [received]
PHST- 2012/04/03 00:00 [revised]
PHST- 2012/04/30 00:00 [accepted]
PHST- 2013/04/11 06:00 [entrez]
PHST- 2013/04/11 06:00 [pubmed]
PHST- 2014/10/10 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - S1064-7481(13)00045-6 [pii]
AID - 10.1016/j.jagp.2013.01.040 [doi]
PST - ppublish
SO  - Am J Geriatr Psychiatry. 2013 May;21(5):450-60. doi: 10.1016/j.jagp.2013.01.040. 
      Epub 2013 Feb 6.