Cited by 92Tryptophan and brain disordersSuicide and Self-Harm StudiesBipolar Disorder and Treatment

Inflammation and lithium: clues to mechanisms contributing to suicide-linked traits

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Beurel, E, Jope, R S·2014·Translational Psychiatry

Abstract

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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Authors
Beurel, E., & Jope, R. S.
Affiliations
University of Miami (US)
Corresponding author
Jope, R S
Venue
Translational Psychiatry
Published
2014-12-16
Volume
4
Issue
12
Pages
e488-e488
ISSN
2158-3188 (ISSN-L)
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
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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