Inflammation and nitro-oxidative stress in current suicidal attempts and current suicidal ideation: a systematic review and meta-analysis

Jirakran, Ketsupar; Tunvirachaisakul, Chavit; Solmi, Marco; Maes, Michaël

doi:10.1038/s41380-021-01407-4

Cited by 61 publications

(38 citation statements)

References 105 publications

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“…To begin, both lifetime and current suicide behaviors are related with increases in most immunological profiles, most notably the IRS and neurotoxicity profiles. Again, in light of the IRS/neurotoxicity hypotheses of suicidal ideation and attempts [ 19 ], the neurotoxic profile and neurotoxic cytokines and chemokines (e.g., IL-2, IL-15, CCL5, and CXCL10) may exacerbate the adverse effects of RONS/OSTOX on suicidal behaviors [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…The immunological response is intimately linked to redox mechanisms, including increased formation of reactive oxygen and nitrogen species (RONS), diminished antioxidant defenses, and indicators of enhanced nitro-oxidative stress toxicity (OSTOX), all of which are found in depression [ 16 , 17 , 18 ]. Suicidal behaviors (SB), both recent and lifetime suicidal ideation and attempts, are associated with activated IRS, CIRS, RONS, and OSTOX pathways [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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The Immune Profile of Major Dysmood Disorder: Proof of Concept and Mechanism Using the Precision Nomothetic Psychiatry Approach

Maes

Rachayon

Jirakran

et al. 2022

Cells

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Major depressive disorder and a major depressive episode (MDD/MDE) are characterized by activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS). In MDD/MDE, recent precision nomothetic psychiatry studies discovered a new endophenotype class, namely major dysmood disorder (MDMD), a new pathway phenotype, namely reoccurrence of illness (ROI), and a new model of the phenome of depression. The aim of the present study is to examine the association between ROI, the phenome of depression, and MDMD’s features and IRS, CIRS, macrophages (M1), T helper (Th)1, Th2, Th17, T regulatory, and growth factor (GF) profiles. Culture supernatants of unstimulated and stimulated (5 μg/mL of PHA and 25 μg/mL of LPS) diluted whole blood of 30 MDD/MDE patients and 20 controls were assayed for cytokines/GF using the LUMINEX assay. MDMD was characterized by increased M1, Th1, Th2, Th17, Treg, IRS, CIRS, neurotoxicity, and GF profiles. Factor analysis shows that ROI features and immune-GF profiles may be combined into a new pathway phenotype (an extracted latent vector). ROI, lifetime and recent suicidal behaviors, and severity of depression are significantly associated with immunotoxicity and GF profiles. Around 80.0% of the variance in the phenome is predicted by ROI and neurotoxicity or the IRS/CIRS ratio. The molecular pathways underpinning ROI-associated sensitization of immune/growth networks are transmembrane receptor protein kinase-triggered STAT protein phosphorylation, TLR/NF-κB, JAK-STAT, and the main proliferation/survival PI3K/Akt/RAS/MAPK pathway. In conclusion, MDMD’s heightened immune responses are the consequence of ROI-associated sensitization combined with immunostimulatory triggers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Immune Profile of Major Dysmood Disorder: Proof of Concept and Mechanism Using the Precision Nomothetic Psychiatry Approach

Maes

Rachayon

Jirakran

et al. 2022

Cells

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“…The third major finding of this study is that the neurotoxic immune profile comprising neurotoxic cytokines and chemokines was not associated with delirium. This contrasts with the increased neurotoxic profiles established in schizophrenia and associated cognitive impairments, mood disorders, and suicide attempts and ideation [ 79 – 81 ]. At the phenomenological level, post-hip fracture operative delirium has an acute onset and is frequently presenting with more positive psychotic features [ 82 ] contrasting with the chronic nature of schizophrenia and mood disorders.…”

Section: Discussionmentioning

confidence: 98%

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

et al. 2022

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Background The objectives of this study were to delineate whether delirium in older adults is associated with activation of the immune-inflammatory response system (IRS) as indicated by activation of M1, T helper (Th)1, and Th17 profiles, and/or by reduced activities of the compensatory immunoregulatory system (CIRS), including Th2 and T regulatory profiles. Methods We recruited 65 older adult patients with a low energy impact hip fracture who underwent hip fracture operation. The CAM-ICU and the Delirium Rating Scale, Revised-98-Thai version (DRS-R-98) were assessed pre-operatively and 1, 2 and 3 days after surgery. Blood samples (day 1 and 2) post-surgery were assayed for cytokines/chemokines using a MultiPlex assay and the neutrophil/lymphocyte ratio. Results We found that delirium and/or the DRS-R-98 score were associated with IRS activation as indicated by activated M1, Th1, Th17 and T cell growth profiles and by attenuated CIRS functions. The most important IRS biomarkers were CXCL8, interleukin (IL)-6, and tumor necrosis factor-α, and the most important CIRS biomarkers were IL-4 and soluble IL-1 receptor antagonist. We found that 42.5% of the variance in the actual changes in the DRS-R-98 score (averaged from day 1 to day 3) was explained by T cell growth factors, baseline DRS-R-98 scores and age. An increase in the NLR reflects overall IRS, M1, Th1, Th17, and Th2 activation. Conclusions Post-hip surgery delirium is associated with activated IRS pathways and appears especially in patients with lowered CIRS functions.

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“…To begin, both lifetime and current suicide behaviors are related with increases in most immunological profiles, most notably the IRS and neurotoxicity profiles. Again, in light of the IRS/neurotoxicity hypotheses of suicidal ideation and attempts [9], the neurotoxic profile and neurotoxic cytokines (e.g., IL-2, IL-15, CCL5, CXCL10) may exacerbate the adverse effects of RONS/OSTOX on suicidal behaviors [9].…”

Section: Immune Profiles and The Features Of Mdmdmentioning

confidence: 99%

“…The immunological response is intimately linked to redox mechanisms including increased formation of reactive oxygen and nitrogen species (RONS), diminished antioxidant defenses, and indicators of enhanced nitro-oxidative stress toxicity (OSTOX), all of which are found in MDD and BD [6][7][8]. Suicidal behaviors (SB), both recent and lifetime suicidal ideation and attempts, are associated with activated IRS, CIRS, RONS, and OSTOX pathways [9].…”

Section: Introductionmentioning

confidence: 99%

The immune profile of Major Dysmood Disorder: proof of concept and mechanism using the precision nomothetic psychiatry approach

Maes

Rachayon

Jirakran

et al. 2022

Preprint

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Major depressive disorder and a major depressive episode (MDD/MDE) are characterized by activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS). In MDD/MDE, recent precision nomothetic psychiatry studies discovered a new endophenotype class namely Major Dysmood Disorder, a new pathway phenotype namely reoccurrence of illness (ROI), and a new model of the phenome of depression. The aim of the present study is to examine the association between ROI, the phenome of depression, and MDMD features and IRS, CIRS, M1, T helper (Th)1, Th2, Th17, Tregulatory, and growth factor (GF) profiles. Culture supernatants of unstimulated and stimulated (5 microg/mL of PHA and 25 microg/mL of LPS) diluted whole blood of 30 MDD/MDE patients and 20 controls were assayed for cytokines/GF using the LUMINEX assay. MDMD was characterized by increased M1, Th1, Th2, Th17, Treg, IRS, CIRS, neurotoxicity and GF profiles. Factor analysis shows that ROI features and immune-GF profiles may be combined into one a new pathway phenotype (an extracted latent vector). ROI, lifetime and recent suicidal behaviors, and severity of depression are significantly associated with immunotoxicity and GF profiles. Around 80.0 percent of the variance in the phenome is predicted by ROI and neurotoxicity or the IRS / CIRS ratio. The molecular pathways underpinning ROI-associated sensitization of immune/growth networks are transmembrane receptor protein kinase triggered STAT protein phosphorylation, TLR/NF-kappaB, JAK-STAT, and the main proliferation/survival PI3K/Akt/RAS/MAPK pathway. In conclusion, MDMD heightened immune responses are the consequence of ROI-associated sensitization combined with immunostimulatory triggers.

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Inflammation and nitro-oxidative stress in current suicidal attempts and current suicidal ideation: a systematic review and meta-analysis

Abstract: doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Cited by 61 publications

References 105 publications

The Immune Profile of Major Dysmood Disorder: Proof of Concept and Mechanism Using the Precision Nomothetic Psychiatry Approach

The Immune Profile of Major Dysmood Disorder: Proof of Concept and Mechanism Using the Precision Nomothetic Psychiatry Approach

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

The immune profile of Major Dysmood Disorder: proof of concept and mechanism using the precision nomothetic psychiatry approach

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