PMID- 25582786
OWN - NLM
STAT- MEDLINE
DCOM- 20151021
LR  - 20240323
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 601
DP  - 2015 Aug 5
TI  - Spine synapse remodeling in the pathophysiology and treatment of depression.
PG  - 20-9
LID - S0304-3940(15)00027-0 [pii]
LID - 10.1016/j.neulet.2015.01.022 [doi]
AB  - Clinical brain imaging and postmortem studies provide evidence of structural and 
      functional abnormalities of key limbic and cortical structures in depressed 
      patients, suggesting that spine synapse connectivity is altered in depression. 
      Characterization of the cellular determinants underlying these changes in 
      patients are limited, but studies in rodent models demonstrate alterations of 
      dendrite complexity and spine density and function that could contribute to the 
      morphological and functional alterations observed in humans. Rodent studies 
      demonstrate region specific effects in chronic stress models of depression, 
      including reductions in dendrite complexity and spine density in the hippocampus 
      and prefrontal cortex (PFC) but increases in the basolateral amygdala and nucleus 
      accumbens. Alterations of spine synapse connectivity in these regions are thought 
      to contribute to the behavioral symptoms of depression, including disruption of 
      cognition, mood, emotion, motivation, and reward. Studies of the mechanisms 
      underlying these effects demonstrate a role for altered brain derived 
      neurotrophic factor (BDNF) signaling that regulates synaptic protein synthesis. 
      In contrast, there is evidence that chronic antidepressant treatment can block or 
      reverse the spine synapse alterations caused by stress. Notably, the new fast 
      acting antidepressant ketamine, which produces rapid therapeutic actions in 
      treatment resistant MDD patients, rapidly increases spine synapse number in the 
      PFC of rodents and reverses the effects of chronic stress. The rapid synaptic and 
      behavioral actions of ketamine occur via increased BDNF regulation of synaptic 
      protein synthesis. Together these studies provide evidence for a neurotophic and 
      synaptogenic hypothesis of depression and treatment response and indicate that 
      spine synapse connectivity in key cortical and limbic brain regions is critical 
      for control of mood and emotion.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Duman, Catharine H
AU  - Duman CH
AD  - Laboratory of Molecular Psychiatry, Department of Psychiatry, Yale University 
      School of Medicine, 34 Park Street, New Haven, CT 06508, USA.
FAU - Duman, Ronald S
AU  - Duman RS
AD  - Laboratory of Molecular Psychiatry, Department of Psychiatry, Yale University 
      School of Medicine, 34 Park Street, New Haven, CT 06508, USA. Electronic address: 
      ronald.duman@yale.edu.
LA  - eng
GR  - R01 MH093897/MH/NIMH NIH HHS/United States
GR  - R01 MH105910/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20150109
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Antidepressive Agents)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/therapeutic use
MH  - Cerebral Cortex/pathology/physiopathology
MH  - Dendritic Spines/*physiology/ultrastructure
MH  - Depression/drug therapy/etiology/pathology/*physiopathology
MH  - Humans
MH  - Limbic System/pathology/physiopathology
MH  - Neurons/pathology
MH  - Stress, Psychological/complications/pathology/physiopathology
MH  - Synapses/*physiology
PMC - PMC4497940
MID - NIHMS655074
OTO - NOTNLM
OT  - Antidepressant
OT  - Glutamate
OT  - Ketamine
OT  - Neurotrophic factor
OT  - Stress
EDAT- 2015/01/15 06:00
MHDA- 2015/10/22 06:00
PMCR- 2016/08/05
CRDT- 2015/01/14 06:00
PHST- 2014/11/05 00:00 [received]
PHST- 2015/01/07 00:00 [revised]
PHST- 2015/01/08 00:00 [accepted]
PHST- 2015/01/14 06:00 [entrez]
PHST- 2015/01/15 06:00 [pubmed]
PHST- 2015/10/22 06:00 [medline]
PHST- 2016/08/05 00:00 [pmc-release]
AID - S0304-3940(15)00027-0 [pii]
AID - 10.1016/j.neulet.2015.01.022 [doi]
PST - ppublish
SO  - Neurosci Lett. 2015 Aug 5;601:20-9. doi: 10.1016/j.neulet.2015.01.022. Epub 2015 
      Jan 9.