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Lithium's antisuicidal efficacy: elucidation of neurobiological targets using endophenotype strategies
Colleen E Kovacsics1, Irving I Gottesman, Todd D Gould
1Department of Psychiatry, Mood and Anxiety Disorders Program, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Abstract:
Lithium used as a drug treatment for major mental disorders such as bipolar disorder and depression is effective in reducing the risk of both attempted and completed suicide. However, the mechanisms underlying lithium's antisuicidal actions are not yet known, limiting the development of novel lithium-mimetic compounds that may help reduce suicide risk with fewer undesirable side effects. Suicide is a complex behavior, complicated to study in humans, and impossible to fully reproduce in animal models. The endophenotype approach, by which quantitative measures of neurobiological function are used to assess and subclassify psychiatric illness, may present a path to new discoveries. Aggression and impulsivity are candidate endophenotypes strongly associated with suicide; we review the evidence supporting aggression and impulsivity as suicide endophenotypes, as well as the effects of lithium on these constructs in both humans and rodents. Examining the mechanisms that contribute to lithium's antiaggressive and antiimpulsive effects may assist in understanding how lithium acts to reduce the risk of suicide and in elucidating the neurobiological underpinnings of suicidal behavior.
Insights
Lithium effectively reduces suicide risk in major mental disorders. Understanding its anti-aggression and anti-impulsivity effects may reveal mechanisms for developing better suicide prevention strategies.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Lithium is a key treatment for bipolar disorder and depression, significantly reducing suicide risk.
- The precise mechanisms behind lithium's antisuicidal effects remain unknown, hindering the development of new treatments.
- Studying suicide is complex due to ethical and modeling limitations in humans and animals.
Purpose of the Study:
- To explore the endophenotype approach for understanding suicide.
- To review evidence linking aggression and impulsivity to suicide.
- To examine lithium's effects on aggression and impulsivity in humans and rodents.
Main Methods:
- Review of existing literature on suicide, endophenotypes, and lithium.
- Analysis of aggression and impulsivity as potential endophenotypes for suicide.
- Examination of lithium's impact on aggression and impulsivity in human and animal studies.
Main Results:
- Aggression and impulsivity are strongly associated with suicide risk.
- Lithium demonstrates anti-aggressive and anti-impulsive effects in both human and rodent models.
- These effects suggest a potential pathway for understanding lithium's antisuicidal actions.
Conclusions:
- Investigating lithium's anti-aggression and anti-impulsivity mechanisms is crucial.
- Elucidating these mechanisms can advance the understanding of suicidal behavior.
- This research may guide the development of novel suicide-reducing therapeutics.
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