Inflammation and lithium: clues to mechanisms contributing to suicide-linked traits
Open accessAbstract
Suicide is one of the leading causes of death in the United States, yet it remains difficult to understand the mechanistic provocations and to intervene therapeutically. Stress is recognized as a frequent precursor to suicide. Psychological stress is well established to cause activation of the inflammatory response, including causing neuroinflammation, an increase of inflammatory molecules in the central nervous system (CNS). Neuroinflammation is increasingly recognized as affecting many aspects of CNS functions and behaviors. In particular, much evidence demonstrates that inflammatory markers are elevated in traits that have been linked to suicidal behavior, including aggression, impulsivity and depression. Lithium is recognized as significantly reducing suicidal behavior, is anti-inflammatory and diminishes aggression, impulsivity and depression traits, each of which is associated with elevated inflammation. The anti-inflammatory effects of lithium result from its inhibition of glycogen synthase kinase-3 (GSK3). GSK3 has been demonstrated to strongly promote inflammation, aggressive behavior in rodents and depression-like behaviors in rodents, whereas regulation of impulsivity by GSK3 has not yet been investigated. Altogether, evidence is building supporting the hypothesis that stress activates GSK3, which in turn promotes inflammation, and that inflammation is linked to behaviors associated with suicide, including particularly aggression, impulsivity and depression. Further investigation of these links may provide a clearer understanding of the causes of suicidal behavior and provide leads for the development of effective preventative interventions, which may include inhibitors of GSK3.
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GSK3 levels are higher in the ventral prefrontal cortex of depressed people who died by suicide.
“is elevated in the ventral PFC of depressed suicide decedents”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [296]
GSK3 promotes inflammation.
“Glycogen synthase kinase-3 (GSK3), an enzyme that promotes inflammation”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [296]
GSK3 is inhibited by lithium.
“and is inhibited by lithium (296).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [296]
GSK3 is linked to animal stress and aggression models.
“is linked to animal stress and aggression models”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [296]
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Role of Inflammation in Suicide: From Mechanisms to Treatment
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“…promising pharmacological target is glycogen synthase kinase-3 (GSK3), which raises the levels of pro-inflammatory cytokines and, thus, is thought to promote the development of aggression and depressive symptoms, which are closely linked to development of suicidality (Beurel and Jope, 2014).”
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- Authors
- Beurel, E., & Jope, R. S.
- Affiliations
- University of Miami (US)
- Corresponding author
- Jope, R S
- ORCID
- Beurel, E
- Venue
- Translational Psychiatry
- Published
- 2014-12-16
- Volume
- 4
- Issue
- 12
- Pages
- e488-e488
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4270310
- OpenAlex
- W2035360924
- Cited by
- 92
- References
- 160
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 13 · 2022: 8 · 2021: 21 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 6 · 2016: 11 · 2015: 5
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- 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
- National Institute of Mental Health (K99MH090236, R00MH090236, MH090236, R56MH038752, MH038752, MH095380, R01MH038752, R01MH095380)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- suicide, neuroinflammation, lithium, glycogen synthase kinase-3, psychological stress, aggression, impulsivity, depression, inflammatory markers, suicide prevention, GSK-3 inhibitors
- MeSH terms
- Suicide Prevention, Aggression, Animals, Depression, Humans, Impulsive Behavior, Inflammation, Lithium, Stress, Psychological, Glycogen Synthase Kinase 3
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