Psychoneuroimmunology: The new frontier in suicide research

Abstract

Elucidating complex, multifactorial phenomena like suicide and suicidal behaviors (SSB) require multidisciplinary fields such as Psychoneuroimmunology (PNI). Indeed, our appreciation of the bidirectional communication channels between the brain and the rest of the body with its immune arsenal as the key player has positioned PNI as a promising field of research. We now know that major psychiatric, behavioral, and somatic disorders related to SSB accompany neuroimmune dysregulation. These disorders range from depression, emotional dysregulation, atopy, and epilepsy to certain viral and parasitic infections. By utilizing epidemiological, genetic, microbial, and molecular approaches, the PNI research community has excogitated novel biomarker candidates and pathways in support of SSB risk stratification at individual level. This remarkable progress in just two previous decades shall, if successful, help implement personalized prevention and treatment strategies, using PNI-assisted tools. The aims of this narrative review and opinion piece are to summarize important discoveries concerning the role of neuroimmune activation in SSB and to highlight important future directions for the field. Major caveats of the findings concerning methodological approaches, clinical reality of frequent comorbid psychopathology, and novel molecular targets are presented. Finally, this review calls on the PNI research community for increased attention towards factors that promote resilience to suicide, while accepting “consciousness” under its wing. Thus, PNI represents the new frontier in suicide research. Future breakthroughs in this discipline shall bring us closer to understanding the biological substrates of qualia i.e., subjective, and experiential meanings of life and death.

Levels of IL-6 are Associated with Lifetime Attempted Suicide in Alcohol Use Disorder Patients

“…We found no differences in cytokine levels between the patients who had attempted suicide and the others for the cytokines IFN-γ, IL-1β, IL-8, IL-10 and TNF-α, despite that these have been shown to be related to suicide attempts in several studies, 10,12,21,22 however less consistently than for IL-6. [42][43][44][45] Again, the lack of findings could be partially explained by the general elevation of cytokines in AUD patients, possibly masking factors that would otherwise be visible.…”

“…18 MD is a major risk factor for suicide and SA, 19,20 and neuroimmunological alterations are also related to suicidal behaviour, with alterations in circulating cytokines having been detected in people with previous SA. 21 The most persistent findings are relations between suicidal behaviour and increased levels of IL-1β, IL-6, IL-8, TNF-α, IFN-γ, and others that have been detected at lower levels. 12,[21][22][23][24] The robustness of associations with IL-1β and IL-6 has led IL-1β and IL-6 to be proposed as clinical biomarkers for suicidal behaviour, however with caution against their clinical applicability, due to the practicalities of cytokine analysis and difficulties in establishing the predictive values of IL-6 on the individual level.…”

“…21 The most persistent findings are relations between suicidal behaviour and increased levels of IL-1β, IL-6, IL-8, TNF-α, IFN-γ, and others that have been detected at lower levels. 12,[21][22][23][24] The robustness of associations with IL-1β and IL-6 has led IL-1β and IL-6 to be proposed as clinical biomarkers for suicidal behaviour, however with caution against their clinical applicability, due to the practicalities of cytokine analysis and difficulties in establishing the predictive values of IL-6 on the individual level. 25 Given the immune activation in both AUD patients and among those with depression and the high co-morbidity between the two, it is of special interest to investigate cytokine levels in AUD patients with or without SA.…”

Integrative Analyses of scRNA-seq, Bulk mRNA-seq, and DNA Methylation Profiling in Depressed Suicide Brain Tissues

“…The risk of suicidal behavior is multifactorial and includes a range of biological, psychiatric, psychosocial, and cultural factors. However, the underlying etiology and biological mechanism of suicidal behavior remains poorly understood ( Docherty et al, 2021 ; Jiang et al, 2021 ; Neupane, 2021 ; Lindner et al, 2022 ). Currently, postmortem brain tissues obtained from suicide victims offer an important avenue to study the neuropathophysiological mechanisms associated with suicide by offering a snapshot of what happened in the brains that led to suicide and death ( Gate et al, 2021 ; Chang et al, 2022 ; Jaffe et al, 2022 ; Kenigsbuch et al, 2022 ).…”

Editorial commentary on the special issue emerging psychoneuroimmunology research: Future leaders in focus

“…Importantly, this commentary recognized the potential for remote online programs to increase accessibility to and participation in MBI interventions. Relatedly, Neupane (2021) argued that as a field, PNI should employ rigorous scientific methods to evaluate the more holistic health perspectives and treatments adopted by some Eastern traditions (e.g., mindful awareness, different exercise forms, diets). Adopting a more global approach and integrating scientific approaches from psychological, neurological, and immunological perspectives may lead to a better understanding of the biological mechanisms underlying mental illnesses and their treatment.…”