PMID- 23462230
OWN - NLM
STAT- MEDLINE
DCOM- 20140123
LR  - 20211021
IS  - 1092-8529 (Print)
IS  - 1092-8529 (Linking)
VI  - 18
IP  - 5
DP  - 2013 Oct
TI  - Second messenger/signal transduction pathways in major mood disorders: moving 
      from membrane to mechanism of action, part I: major depressive disorder.
PG  - 231-41
LID - 10.1017/S1092852913000059 [doi]
AB  - The etiopathogenesis and treatment of major mood disorders have historically 
      focused on modulation of monoaminergic (serotonin, norepinephrine, dopamine) and 
      amino acid [gamma-aminobutyric acid (GABA), glutamate] receptors at the plasma 
      membrane. Although the activation and inhibition of these receptors acutely alter 
      local neurotransmitter levels, their neuropsychiatric effects are not immediately 
      observed. This time lag implicates intracellular neuroplasticity as primary in 
      the mechanism of action of antidepressants and mood stabilizers. The modulation 
      of intracellular second messenger/signal transduction cascades affects 
      neurotrophic pathways that are both necessary and sufficient for monoaminergic 
      and amino acid-based treatments. In this review, we will discuss the evidence in 
      support of intracellular mediators in the pathophysiology and treatment of 
      preclinical models of despair and major depressive disorder (MDD). More 
      specifically, we will focus on the following pathways: cAMP/PKA/CREB, 
      neurotrophin-mediated (MAPK and others), p11, Wnt/Fz/Dvl/GSK3beta, and NFkappaB/DeltaFosB. 
      We will also discuss recent discoveries with rapidly acting antidepressants, 
      which activate the mammalian target of rapamycin (mTOR) and release of inhibition 
      on local translation via elongation factor stimulation. Throughout this 
      discourse, we will highlight potential intracellular targets for therapeutic 
      intervention. Finally, future clinical implications are discussed.
FAU - Niciu, Mark J
AU  - Niciu MJ
AD  - 1 National Institutes of Health (NIH)/National Institute of Mental Health (NIMH), 
      Experimental Therapeutics and Pathophysiology Branch (ETPB), Intramural Research 
      Program, Bethesda, Maryland, USA.
FAU - Ionescu, Dawn F
AU  - Ionescu DF
FAU - Mathews, Daniel C
AU  - Mathews DC
FAU - Richards, Erica M
AU  - Richards EM
FAU - Zarate, Carlos A Jr
AU  - Zarate CA Jr
LA  - eng
GR  - Z99 MH999999/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Review
DEP - 20130305
PL  - United States
TA  - CNS Spectr
JT  - CNS spectrums
JID - 9702877
SB  - IM
MH  - Depressive Disorder, Major/*metabolism
MH  - Humans
MH  - Second Messenger Systems/*physiology
MH  - Signal Transduction/physiology
PMC - PMC4955397
MID - NIHMS435405
EDAT- 2013/03/07 06:00
MHDA- 2014/01/24 06:00
PMCR- 2016/07/21
CRDT- 2013/03/07 06:00
PHST- 2013/03/07 06:00 [entrez]
PHST- 2013/03/07 06:00 [pubmed]
PHST- 2014/01/24 06:00 [medline]
PHST- 2016/07/21 00:00 [pmc-release]
AID - S1092852913000059 [pii]
AID - 10.1017/S1092852913000059 [doi]
PST - ppublish
SO  - CNS Spectr. 2013 Oct;18(5):231-41. doi: 10.1017/S1092852913000059. Epub 2013 Mar 
      5.