Neural and molecular correlates of psychological pain during major depression, and its link with suicidal ideas

Jollant, Fabrice; Perreira, Fabricio; Fiori, Laura M.; Richard‐Devantoy, Stéphane; Lutz, Pierre-Eric; Belzeaux, Raoul; Turecki, Gustavo

doi:10.1016/j.pnpbp.2020.109909

Cited by 18 publications

(13 citation statements)

References 57 publications

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“…Although mental pain does not necessarily lead to suicidal ideas, recent studies suggest that individuals with severe suicidal ideas (notably those with a plan) also have high levels of mental pain. 33 Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain. Indirect support for this suggestion is the observation that the effects of ketamine on depression might involve the opioid system 34 (although this is controversial 35 ), that buprenorphine—a μ opioid partial agonist—is also effective on suicidal ideas, 36 and that mental pain has been associated with the nociceptin system.…”

Section: Discussionmentioning

confidence: 99%

“…Our study suggests that the beneficial effect of ketamine on suicidal ideation could be mediated by an effect on psychological pain. Although mental pain does not necessarily lead to suicidal ideas, recent studies suggest that individuals with severe suicidal ideas (notably those with a plan) also have high levels of mental pain 33. Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain.…”

Section: Discussionmentioning

confidence: 99%

“…Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain. Indirect support for this suggestion is the observation that the effects of ketamine on depression might involve the opioid system34 (although this is controversial35), that buprenorphine—a μ opioid partial agonist—is also effective on suicidal ideas,36 and that mental pain has been associated with the nociceptin system 33…”

Section: Discussionmentioning

confidence: 99%

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Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial

Abbar

Dematteï

El‐Hage

et al. 2022

BMJ

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Objective To confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group. Design Prospective, double blind, superiority, randomised placebo controlled trial. Setting Seven French teaching hospitals between 13 April 2015 and 12 March 2019. Eligibility criteria for participants Aged 18 or older with current suicidal ideation, admitted to hospital voluntarily. Exclusion criteria included a history of schizophrenia or other psychotic disorders, substance dependence, and contraindications for ketamine. Participants 156 participants were recruited and randomised to placebo (n=83) or ketamine (n=73), stratified by centre and diagnosis: bipolar, depressive, or other disorders. Intervention Two 40 minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) were administered at baseline and 24 hours, in addition to usual treatment. Main outcome measures The primary outcome was the rate of patients in full suicidal remission at day 3, according to the scale for suicidal ideation total score ≤3. Analyses were conducted on an intention-to-treat basis. Results More participants receiving ketamine reached full remission of suicidal ideas at day 3 than those receiving placebo: 46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm (odds ratio 3.7 (95% confidence interval 1.9 to 7.3), P<0.001). This effect differed according to the diagnosis (treatment: P<0.001; interaction: P=0.02): bipolar (odds ratio 14.1 (95% confidence interval 3.0 to 92.2), P<0.001), depressive (1.3 (0.3 to 5.2), P=0.6), or other disorders (3.7 (0.9 to 17.3, P=0.07)). Side effects were limited. No manic or psychotic symptom was seen. Moreover, a mediating effect of mental pain was found. At week 6, remission in the ketamine arm remained high, although non-significantly versus placebo (69.5% v 56.3%; odds ratio 0.8 (95% confidence interval 0.3 to 2.5), P=0.7). Conclusions The findings indicate that ketamine is rapid, safe in the short term, and has persistent benefits for acute care in suicidal patients. Comorbid mental disorders appear to be important moderators. An analgesic effect on mental pain might explain the anti-suicidal effects of ketamine. Trial registration ClinicalTrials.gov NCT02299440 .

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial

Abbar

Dematteï

El‐Hage

et al. 2022

BMJ

Self Cite

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“…Apart from the cytokines involvement in contributing to the pathophysiology of suicidal behavior include activation of the kynurenine pathway, dysregulation of the HPA axis, and alterations in monoamine metabolism. QUIN, an N-methyl-D-aspartic acid receptor agonist and acts via activation of the NR1, NR2A, and NR2B NMDA receptors (( Jollant et al., 2020 ). Further, Tonelli et al.…”

Section: Psychoneuroimmunological Suicidal Changes In Adolescentsmentioning

confidence: 99%

Psychological and neurobiological aspects of suicide in adolescents: Current outlooks

Vargas-Medrano

Diaz-Pacheco

Castaneda

et al. 2020

Brain, Behavior, & Immunity - Health

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Suicidality is one of the leading causes of death among young adults in the United States and represents a significant health problem worldwide. The suicide rate among adolescents in the United States has increased dramatically in the latest years and has been accompanied by considerable changes in youth suicide, especially among young girls. Henceforth, we need a good understanding of the risk factors contributing to suicidal behavior in youth. An explanatory model for suicidal behavior that links clinical and psychological risk factors to the underlying neurobiological, neuropsychological abnormalities related to suicidal behavior might predict to help identify treatment options and have empirical value. Our explanatory model proposes that developmental, biological factors (genetics, proteomics, epigenetics, immunological) and psychological or clinical (childhood adversities) may have causal relevance to the changes associated with suicidal behavior. In this way, our model integrates findings from several perspectives in suicidality and attempts to explain the relationship between various neurobiological, genetic, and clinical observations in suicide research, offering a comprehensive hypothesis to facilitate understanding of this complex outcome. Unraveling the knowledge of the complex interplay of psychological, biological, sociobiological, and clinical risk factors is highly essential, concerning the development of effective prevention strategy plans for suicidal ideation and suicide.

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“…Fortunately, with the advances of high-throughput sequencing analyses, noval core genes and pathways have been demonstrated to be correlated with the genesis and progression of depression. For example, Jollant F et al demonstrated that the serotonergic and nociceptin systems are associated with the activity of depression using peripheral transcriptomic analyses [3]. Nilay et al discovered that Plenty of evidence for IFN-α related molecular biological mechanisms related to depression through whole-blood transcriptomic analyses [4].…”

Section: Introductionmentioning

confidence: 99%

Identification of Core Genes and Pathways in Major Depressive Disorder Applying Bioinformatics

Yang

Yin

Wang

et al. 2020

Preprint

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Background: Although extensive study efforts on major depressive disorder (MDD), the pathogenesis related to the biological factors are not fully understood and present therapeutic regimen are ineffective in some depressive patients. This study aims to identify key genes and pathways associated with the molecular biological mechanisms of major depressive disorder through bioinformatics analysis in the Gene Expression Omnibus (GEO) public database of the National Center for Biotechnology Information (NCBI) website.Materials and methods: The whole-transcriptome brain expression profile dataset (GSE101521) was obtained from the GEO database. Differentially-expressed genes (DEGs) in normal group (non-psychiatric human) and MDD group (depressive patients) were identified applying Networkanalyst online database. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to function annotation and enrichment analysis. After that, STRING online database was conducted to protein–protein interaction (PPI) network, and Cytoscape.3.7.2 software was performed to module analysis. Results: Out of the 41 DEGs identified from normal tissue samples and MDD, 39 were upregulated and 2 were downregulated. GO enrichment analysis discovered that DEGs were primarily involved in inflammatory response, and KEGG pathway analysis suggested that the most chiefly pathway related to MDD were IL-17 signaling pathway, TNF signaling pathway and NOD-like receptor signaling pathway. Six hub genes (IL6, CXCL8, IL1B, FOS, CCL2 and CXCL2) were identified by PPI network and module analysis. Conclusion: Our current study detected novel markers and targets involved immune system, which are involved in pivotal biological mechanisms related to the pathogenesis of major depression. Looking forward, these findings still need to be validated in future experimental studies.

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Neural and molecular correlates of psychological pain during major depression, and its link with suicidal ideas

Cited by 18 publications

References 57 publications

Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial

Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial

Psychological and neurobiological aspects of suicide in adolescents: Current outlooks

Identification of Core Genes and Pathways in Major Depressive Disorder Applying Bioinformatics

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