Document Type
Journal Article
Publication Date
10-2013
Journal
CNS Spectrums
Volume
Volume 18, Issue 5
Inclusive Pages
242-251
Abstract
The etiopathogenesis and treatment of major mood disorders have historically focused on modulation of monoaminergic (serotonin, norepinephrine, dopamine) and amino acid [γ-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/GSK3β, and NFκB/ΔFosB. 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.
APA Citation
Niciu, M.J., Ionescu, D.F., Mathews, D.C., Richards, E.M., Zarate, C.A. (2013). Second messenger/signal transduction pathways in major mood disorders: Moving from membrane to mechanism of action, part II: bipolar disorder. CNS Spectrums, 18(5), 242-251.
Peer Reviewed
1
Open Access
1
Comments
Published version is available at dx.doi.org/10.1017/S1092852913000059. Copyright © 2013 Cambridge University Press.