Cited by 100Bipolar Disorder and TreatmentNeuroinflammation and Neurodegeneration MechanismsTryptophan and brain disorders

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

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Watkins, C C, Sawa, A, Pomper, M G·2014·Translational 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.

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  • Activation of Gi-coupled pathways on pvMΦs via 5-HT1B receptors is a potential mechanism for the regulation of macrophage polarization and inflammatory responses by tonic 5-HT release within the DRN.

    “Activation of Gi-coupled pathways on pvMΦs via 5-HT1B receptors is also a potential mechanism for the regulation of macrophage polarization and inflammatory responses by tonic 5-HT release within the DRN, which may be relevant to the increasing importance of neuroinflammatory pathways in the etiology of psychiatric disorders (Brisch et al., 2017; Howerton et al., 2014; Watkins et al., 2014).”

    From Molecular and anatomical organization of the dorsal raphe nucleus (2019) · cites this paper as Watkins et al., 2014

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Authors
Watkins, C. C., Sawa, A., & Pomper, M. G.
Affiliations
Johns Hopkins University (US)
Corresponding author
Watkins, C C
Venue
Translational Psychiatry
Published
2014-01-21
Volume
4
Issue
1
Pages
e350-e350
ISSN
2158-3188 (ISSN-L)
OpenAlex
W2070899132
Cited by
100
References
148
Citations by year
2026: 4 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 11 · 2018: 6 · 2017: 9 · 2016: 18 · 2015: 11 · 2014: 8
FWCI
2.11
Type
journal article
Language
en
Open access
Locations
  • Translational Psychiatry (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Johns Hopkins University
  • National Institute of Mental Health (T32MH015330, P50MH094268)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (K08HD073315)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
bipolar disorder, microglia, neuroinflammation, immune cell signaling, glycogen synthase kinase-3β, Wnt signaling, lithium, valproic acid, mood stabilizers, serotonergic system, bipolar depression, bipolar mania, neurotransmitter synthesis, neuroimaging
MeSH terms
Bipolar Disorder, Humans, Inflammation, Neuropharmacology, Signal Transduction, Microglia, Molecular Imaging

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