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Second messenger/signal transduction pathways in major mood disorders: moving from membrane to mechanism of action, part II: bipolar disorder

Published online by Cambridge University Press:  11 March 2013

Mark J. Niciu ,
Dawn F. Ionescu ,
Daniel C. Mathews ,
Erica M. Richards  and
Carlos A. Zarate Jr.
Mark J. Niciu*
Affiliation:
National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, Bethesda, Maryland, USA
Dawn F. Ionescu
Affiliation:
National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, Bethesda, Maryland, USA
Daniel C. Mathews
Affiliation:
National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, Bethesda, Maryland, USA
Erica M. Richards
Affiliation:
National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, Bethesda, Maryland, USA
Carlos A. Zarate Jr.
Affiliation:
National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, Bethesda, Maryland, USA Psychiatry and Behavioral Sciences, The George Washington University, Washington, DC, USA
*
*Address for correspondence: Dr. Mark J. Niciu, National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, 10 Center Dr., Building 10/CRC, Room 7-5545, Bethesda, MD 20814-9692, USA. (Email [email protected])
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Abstract

In this second of two articles on second messenger/signal transduction cascades in major mood disorders, we will review the evidence in support of intracellular dysfunction and its rectification in the etiopathogenesis and treatment of bipolar disorder (BD). The importance of these cascades is highlighted by lithium's (the gold standard in BD psychopharmacology) ability to inhibit multiple critical loci in second messenger/signal transduction cascades including protein kinase C (involved in the IP3/PIP2 pathway) and GSK-3β (canonically identified in the Wnt/Fz/Dvl/GSK-3β cascade). As a result, and like major depressive disorder (MDD), more recent pathophysiological studies and rational therapeutic targets have been directed at these and other intracellular mediators. Even in the past decade, intracellular dysfunction in numerous neuroprotective/apoptotic cascades appears important in the pathophysiology and may be a future target for pharmacological interventions of BD.

Keywords

Bipolar disordersignal transductionsecond messengerintracellular cascadesmood stabilizerslithium
Type
Review Articles
Information
CNS Spectrums , Volume 18 , Issue 5 , October 2013 , pp. 242 - 251
Copyright
Copyright © Cambridge University Press 2013 

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Footnotes

The authors gratefully acknowledge the support of the Intramural Research Program of the NIMH/NIH (IRP-NIMH/NIH; Bethesda, MD, USA), and thank the 7SE Inpatient Mood and Anxiety Disorders Research Unit of the NIMH/NIH for their support. Funding for this work was supported by the IRP-NIMH-NIH by a NARSAD Independent Investigator to C.A.Z., and by the Brain & Behavior Mood Disorders Research Award to C.A.Z.

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