Effects of stress on endophenotypes of suicide across species: A role for ketamine in risk mitigation

Lamontagne, Steven J; Ballard, Elizabeth D.; Zarate, Carlos A.

doi:10.1016/j.ynstr.2022.100450

Cited by 5 publications

(3 citation statements)

References 286 publications

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“…This suggests a possible mechanism by which early life adversity may increase the risk of suicide. Lamontagne et al (2022) also highlighted the candidate endophenotypes of suicide risks, such as sleep disturbances, changes in the 5-HT2A receptor expression associated with suicide in humans and chronic stress in animals, as well as effects of ketamine [87]. These mechanisms are complementary to those summarized here.…”

Section: An Approach Of Impulsivity-aggressiveness In Rodentsmentioning

confidence: 84%

Pharmacological Mechanism of Ketamine in Suicidal Behavior Based on Animal Models of Aggressiveness and Impulsivity: A Narrative Review

et al. 2023

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Around 700,000 people die from suicide each year in the world. Approximately 90% of suicides have a history of mental illness, and more than two-thirds occur during a major depressive episode. Specific therapeutic options to manage the suicidal crisis are limited and measures to prevent acting out also remain limited. Drugs shown to reduce the risk of suicide (antidepressants, lithium, or clozapine) necessitate a long delay of onset. To date, no treatment is indicated for the treatment of suicidality. Ketamine, a glutamate NMDA receptor antagonist, is a fast-acting antidepressant with significant effects on suicidal ideation in the short term, while its effects on suicidal acts still need to be demonstrated. In the present article, we reviewed the literature on preclinical studies in order to identify the potential anti-suicidal pharmacological targets of ketamine. Impulsive–aggressive traits are one of the vulnerability factors common to suicide in patients with unipolar and bipolar depression. Preclinical studies in rodent models with impulsivity, aggressiveness, and anhedonia may help to analyze, at least in part, suicide neurobiology, as well as the beneficial effects of ketamine/esketamine on reducing suicidal ideations and preventing suicidal acts. The present review focuses on disruptions in the serotonergic system (5-HTB receptor, MAO-A enzyme), neuroinflammation, and/or the HPA axis in rodent models with an impulsive/aggressive phenotype, because these traits are critical risk factors for suicide in humans. Ketamine can modulate these endophenotypes of suicide in human as well as in animal models. The main pharmacological properties of ketamine are then summarized. Finally, numerous questions arose regarding the mechanisms by which ketamine may prevent an impulsive–aggressive phenotype in rodents and suicidal ideations in humans. Animal models of anxiety/depression are important tools to better understand the pathophysiology of depressed patients, and in helping develop novel and fast antidepressant drugs with anti-suicidal properties and clinical utility.

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Section: An Approach Of Impulsivity-aggressiveness In Rodentsmentioning

confidence: 84%

Pharmacological Mechanism of Ketamine in Suicidal Behavior Based on Animal Models of Aggressiveness and Impulsivity: A Narrative Review

et al. 2023

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“…Our group has recently explored the development of objective laboratory-based tasks in suicide research and described the potential for animal models to inform suicide biomarkers and treatment efforts (Lamontagne et al, 2022 ). This much-needed endeavor has only begun to garner attention in the field, as a growing number of suicide researchers appreciate the need to complement self-reports with objective measures.…”

Section: Introductionmentioning

confidence: 99%

Leveraging a cross-species probabilistic reward task (PRT) in suicide research. A commentary on Luc and Kangas (2024)

Lamontagne,

Zarate,

Ballard

2024

Cogn Affect Behav Neurosci

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“…It is estimated that around 750,000-800,000 people lose their lives to suicide each year, and suicide rates appear to be rising in several low-and middle-income countries [1,2]. Suicide is a complex phenomenon, representing the result of non-linear interactions between innate genetic or developmental vulnerability [3][4][5], current life stressors or events [6], and individual or social protective factors [7]. Suicide attempts are preceded by suicidal ideation and planning, but suicidal ideation is relatively common in the general population, and many individuals with such ideas do not progress to making a suicide attempt [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Pharmacotherapy for the Secondary Prevention of Suicide: Leads from the Social Pain Hypothesis

Rajkumar¹

2022

Preprint

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Suicidal behaviour is a public health problem whose magnitude is both substantial and increasing. Since many individuals seek medical treatment following a suicide attempt, strategies aimed at reducing further attempts in this population are a valid and feasible secondary prevention approach. An evaluation of the available evidence suggests that existing treatment approaches have limited efficacy in this setting, highlighting the need for innovative approaches to suicide prevention. Existing research on the neurobiology of social pain has highlighted the importance of this phenomenon as a risk factor for suicide, and has also yielded several attractive targets for pharmacological preventive strategies. In this paper, the available evidence related to these targets is synthesized and critically evaluated. The way in which social pain is related to the “anti-suicidal” properties of recently approved treatments, such as ketamine and psilocybin, is also examined. Such strategies may be effective for the short-term reduction of suicidal ideation and behaviour in individuals who have made a suicide attempt suicide prevention, particularly in cases where social pain is identified as a contributory factor. These pharmacological approaches may be effective regardless of the presence or absence of a specific psychiatric diagnosis.

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Effects of stress on endophenotypes of suicide across species: A role for ketamine in risk mitigation

Cited by 5 publications

References 286 publications

Pharmacological Mechanism of Ketamine in Suicidal Behavior Based on Animal Models of Aggressiveness and Impulsivity: A Narrative Review

Pharmacological Mechanism of Ketamine in Suicidal Behavior Based on Animal Models of Aggressiveness and Impulsivity: A Narrative Review

Leveraging a cross-species probabilistic reward task (PRT) in suicide research. A commentary on Luc and Kangas (2024)

Pharmacotherapy for the Secondary Prevention of Suicide: Leads from the Social Pain Hypothesis

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