Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Jan 21;4(1):e350.
doi: 10.1038/tp.2013.119.

Glia and immune cell signaling in bipolar disorder: insights from neuropharmacology and molecular imaging to clinical application

C C Watkins  1 , A Sawa  1 , M G Pomper  2
Affiliations
Review

Glia and immune cell signaling in bipolar disorder: insights from neuropharmacology and molecular imaging to clinical application

C C Watkins et al. Transl Psychiatry. .

Abstract

Bipolar disorder (BD) is a debilitating mental illness characterized by severe fluctuations in mood, sleep, energy and executive functioning. Pharmacological studies of selective serotonin reuptake inhibitors and the monoamine system have helped us to clinically understand bipolar depression. Mood stabilizers such as lithium and valproic acid, the first-line treatments for bipolar mania and depression, inhibit glycogen synthase kinase-3 beta (GSK-3β) and regulate the Wnt pathway. Recent investigations suggest that microglia, the resident immune cells of the brain, provide a physiological link between the serotonin system and the GSK-3β/Wnt pathway through neuroinflammation. We review the pharmacological, translational and brain imaging studies that support a role for microglia in regulating neurotransmitter synthesis and immune cell activation. These investigations provide a model for microglia involvement in the pathophysiology and phenotype of BD that may translate into improved therapies.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Proposed role of activated microglia in the modulation of inflammatory mediators, neurotransmitter synthesis and synaptic plasticity in bipolar disorder (BD). CRP, C-reactive protein; IDO, indoindoleamine 2,3-dioxygenase; 5-HT-serotonin; RNS, reactive nitrogen species; ROS, reactive oxygen species.
Figure 2
Figure 2
The Wnt/GSK- 3β pathway.
Figure 3
Figure 3
Microglia express TSPO and Beta-catenin that connect monoamine synthesis and the Wnt pathway. (5-HTT, serotonin transporter; CRP, C-reactive protein; 5-HT, serotonin; TSPO, translocator protein).
See this image and copyright information in PMC

References

    1. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatr. 2005;62:617–627. - PMC - PubMed
    1. Bartels SJ, Forester B, Miles KM, Joyce T. Mental health service use by elderly patients with bipolar disorder and unipolar major depression. Am J Geriatr Psychiatry. 2000;8:160–166. - PubMed
    1. Stensland MD, Schultz JF, Frytak JR. Depression diagnoses following the identification of bipolar disorder: costly incongruent diagnoses. BMC Psychiatry. 2010;10:39. - PMC - PubMed
    1. Begley CE, Annegers JF, Swann AC, Lewis C, Coan S, Schnapp WB, et al. The lifetime cost of bipolar disorder in the US: an estimate for new cases in 1998. PharmacoEconomics. 2001;19 ((Pt 1:483–495. - PubMed
    1. Association AP. Clinical Practice Guidelines2005 , http://www.psychiatry.org/practice/clinical-practice-guidelines . Accessed August 2013.

Publication types